297 Sentences With "tolerability" | Random Sentence Generator

Karuna's drug tolerability "is a big win," Paul said Friday.

Sandrock said the study will mainly look at safety and tolerability.

Berger called the drug "exquisitely combinable" given its safety and tolerability profile so far.

Skorney says the choice between Aimmune's and DBV's treatments may come down to efficacy versus tolerability.

"Interestingly, it looks similar to our other seizure medications in terms of efficacy and tolerability," Porter said.

There were no unexpected safety or tolerability signals for PT010 identified in the 24-week trial, it added.

With demonstrated efficacy, safety, and tolerability, the drug could be a game-changer for children living with HIV.

"With a strong label and better tolerability profile, Xiidra could do even better," said Berenberg Bank analyst Alistair Campbell.

"Not only are some of the drugs not effective for every patient, but then there's this issue with tolerability," she said.

The NIH will then lead the first in-human studies of the vaccine with a primary focus on safety and tolerability.

Delaney's work, she says, "is very important, saving lives and improving the tolerability of these transplants and the success of these transplants".

The early-stage study will enroll 40 healthy subjects and evaluate safety, tolerability and immune response generated by the vaccine GLS-5700.

Earlier today, the companies announced a phase I study with 40 healthy subjects to evaluate the safety, tolerability, and efficacy of the drug.

The trial was being conducted in a licensed private institution to evaluate the safety and tolerability of a particular molecule in health volunteers.

The company said rapastinel was well tolerated and demonstrated a safety and tolerability profile similar to placebo in all three pivotal clinical trials.

" The administration also said in a report that the homelessness crisis had been aggravated by increasing the "tolerability of sleeping on the streets.

Due to the rising threat of microbial resistance, along with concerns over antibiotic tolerability and impact on intestinal microflora, new CABP treatments are needed.

The company's clinical study investigated the efficacy, safety and tolerability of an oral dose of tafamidis capsules compared with a placebo in 441 patients.

Small, with very few participants and no randomization or other controls, the research was similar to "safety and tolerability" studies designed to prove no harm.

The notion that a new drug, which still faced questions about safety and tolerability, could damage Shire's hemophilia franchise overnight was not "super realistic", he added.

The drug, which is being acquired by Johnson & Johnson as part of its $30 billion Actelion takeover, demonstrated acceptable safety and tolerability, the Swiss company said.

In fact, findings from the first known scientific study investigating safety and tolerability of low-dose LSD were slated to go public at Psychedelic Science last weekend.

For now, Rex recommended that patients should speak with their doctors about ways to improve the tolerability and cleansing effect of their preparation process before a colonoscopy.

PLATINUM-BASED CHEMOTHERAPY * ASTRAZENECA - SAFETY AND TOLERABILITY PROFILES OBSERVED IN GY004 WERE GENERALLY CONSISTENT WITH THOSE KNOWN FOR EACH MEDICINE Source text for Eikon: Further company coverage:

Tilray will work with the University of California San Diego Center for Medicinal Cannabis Research to study the safety, tolerability and efficacy of marijuana for a neurological disorder.

Basing treatment decisions on cost rather than clinical considerations also ignores important variations that may exist among patients in terms of safety, efficacy and tolerability in drug classes.

After getting approval to conduct a phase I safety trial, the institute will treat 10 to 12 patients to check safety and tolerability of stem cell-based eye tissue transplants.

"The tolerability really stood out to me, especially since the effectiveness against acne is on par with other tretinoin medications that are far more drying and irritating," Dr. Lain says.

Testing for safety and tolerability The trial will begin in a few weeks, according to a press release published by Inovio Pharmaceuticals, one of the two companies behind the vaccine.

All you need in order to enjoy and appreciate her work is an acute feeling of melancholy that can be massaged into tolerability by a nice cat and some bubble wrap.

"We are pleased with the favorable results of our ACHIEVE I study, which support the efficacy, safety and tolerability profile of ubrogepant," said David Nicholson, Allergan's chief research and development officer.

Corbus last week announced positive data from a study testing anabasum's safety and tolerability as an add-on therapy for CF, a genetic disorder characterized by a progressive loss of lung function.

Abemaciclib could steal a march over its rivals, should data show a higher relative response rate and longer duration of response, as well as good tolerability despite the frequent diarrhea, Anderson added.

BASF, the world's largest chemicals group by sales, is developing improved plant characteristics such as drought tolerability but relies on partners, the biggest being Monsanto, to bring finished seed products to market.

ESMO spokesman Enriqueta Felip of Spain's Vall d'Hebron Institute of Oncology said Tagrisso's edge over older medicines and its good tolerability meant it should be considered a new first-line treatment option.

Tilray said Tuesday that it will work with the University of California San Diego Center for Medicinal Cannabis Research to study the safety, tolerability and efficacy of marijuana for a neurological disorder.

The Swiss company, which said cadazolid demonstrated an acceptable tolerability and safety profile, now plans to analyze the full study results and make them available at upcoming congresses and in peer-reviewed publications.

The Vancouver Island, Canada-based company plans to work with the University of California San Diego Center for Medicinal Cannabis Research to study the safety, tolerability and efficacy of marijuana for a neurological disorder.

"The indication clearly helps differentiate this CDK 4/6 inhibitor from its competitor Ibrance, which so far benefited from a 2-years lead... and a milder tolerability profile," said Baader Helvea analyst Bruno Bulic.

If that's not the case, or if there are any safety or tolerability issues -- for example, if someone's blood pressure goes up when taking the drug phentermine -- it's probably time to try a different drug.

The trials evaluated the efficacy, safety and tolerability of Allergan's treatment, rapastinel, compared to placebo, both in combination with antidepressant therapy (ADT) in patients with depression who had a partial response to ADT, the company said.

Peter and Beverly Pickford's "Wild Land" may be the most bearable and beautiful of the three large coffee-table books; although to be fair, neither beauty nor tolerability is the primary concern of the first two.

GSK showed in drug trials last year that the once-a-day Dovato pill was as good as a standard three-drug cocktail in suppressing the virus that causes AIDS and also in terms of tolerability.

In a move likely foreshadowing broader pharmaceutical application, the company will work with the University of California San Diego Center for Medicinal Cannabis Research to study the safety, tolerability and efficacy of marijuana for a neurological disorder.

"It is still unclear if Bryhali will be labeled for longer-term use, but we are encouraged by the press release which hints at tolerability benefits over Ultravate and a longer dosing regimen," Mizuho analyst Irina Koffler said in a note.

Subjects in the 12-week study will receive a once-daily oral treatment with the objective of proving its safety, tolerability and efficacy in treating tics in adults with Tourette's, a neurological disorder characterized by repetitive, involuntary movements and vocalizations.

"Antidepressants are routinely used worldwide yet there remains considerable debate about their effectiveness and tolerability," said John Ioannidis of Stanford University in the United States, who worked on a team of researchers led by Andrea Cipriani of Britain's Oxford University.

Gene editing has attracted controversy over the past few months, but Editas recently got federal approval to work on a small clinical trial to test the safety, tolerability and efficacy of a gene-editing medicine in patients who have a rare eye disorder.

The poster presentations will feature data from the Company's ongoing Phase 2a clinical study in patients with mild-to-moderate Alzheimer's disease, highlighting ANAVEX 21-2844 dose-response effect, Maximum Tolerated Dose (MTD) determination, as well as, 2689 week safety, tolerability and exploratory efficacy assessment.

Housing organizations have already dismantled the report and the recommendations it floated, like rolling back rent control and building codes—such measures are too expensive for developers who would otherwise build more housing, the report laments—and ending "the tolerability of sleeping on the streets" through increased policing.

Nabriva believes lefamulin is well positioned for use as a first-line empiric monotherapy for the treatment of moderate to severe CABP due to its novel mechanism of action, targeted spectrum of activity, resistance profile, achievement of substantial drug concentration in lung tissue and fluid, oral and IV formulations and favorable tolerability profile.

"We are encouraged by the results observed in the SOLAR-1 study and look forward to submitting the data to an upcoming medical congress and starting discussions with health authorities worldwide," said Samit Hirawat, the head of Novartis Oncology Global Drug Development, adding this was the first such drug to show not only benefits but also tolerability.

The council's report Monday also said the current homeless count may be underestimated, primarily in places like California, New York City, Boston, and Washington, D.C. In placing blame, the report also argued there's too much "tolerability" for homeless people to sleep on the streets due to warm weather, less policing, and shelters — like those in New York — offering privacy or independent rooms.

In these studies, preliminary evidence of efficacy, tolerability, safety, and pharmacokinetics was observed.

Clinical evidence is available to support a particularly good profile in terms of gastrointestinal tolerability.

TCAs have comprehensive effects on various neurotransmitters receptors, which leads to lack of tolerability and increased risk of toxicity.

ABTL0812 showed efficacy in Phase I clinical trials in patients with advanced cancer, with low toxicity and high tolerability.

Tolerability refers to the degree to which overt adverse effects of a drug can be tolerated by a patient. Tolerability of a particular drug can be discussed in a general sense, or it can be a quantifiable measurement as part of a clinical study. Usually, it is measured by the rate of "dropouts", or patients that forfeit participation in a study due to extreme adverse effects. Tolerability, however, is often relative to the severity of the medical condition a drug is designed to treat.

Afterward, the scientists asked the volunteers to rate the tolerability or unpleasantness of the session, on a scale from 1 to 20.

NSAIDs within a group tend to have similar characteristics and tolerability. There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses. Rather, differences among compounds usually relate to dosing regimens (related to the compound's elimination half-life), route of administration, and tolerability profile. Regarding adverse effects, selective COX-2 inhibitors have lower risk of gastrointestinal bleeding.

All adverse reactions reported were mild to moderate in severity and temporary only. The most common reactions (incidence < 1%) were injection- site pain (3.9% of patients), injection-site erythema (1.7%) and injection- site irritation (1.2%). There was no overall difference in the tolerability of florbetaben between different age populations. Repeated annual florbetaben injections showed no differences in the tolerability profile.

Used to increase tolerability of bitter medication or merely to compel consumption, medicated candies or sugar-coated pills can be referred to as dragées.

AG has largely been superseded by medications with better effectiveness and tolerability and reduced toxicity, such as ketoconazole, abiraterone acetate, and other aromatase inhibitors.

Pakistan, Kapadia N, Ghouri S. Efficacy, safety and tolerability of mometasome furoate 0.1% cream, ointment and lotion in childhood eczema. J Pakistan Ass Dermatol 2008; 18; 93-96.

A Phase II open-label clinical study for long-term evaluation of efficacy, safety, tolerability, and pharmacokinetics of RT001 in the treatment of Infantile Neuroaxonal Dystrophy started in the Summer 2018.

Adverse events observed included constipation, acidity, nausea, fatigue and headache, and were of mild to moderate intensity. In all clinical studies, troxipide was well tolerated. In a comparative study with ranitidine, troxipide was assessed as a more tolerable medication than ranitidine. A favorable tolerability profile for troxipide was reported by 95.45% of the investigators as compared to 65.45% for ranitidine while favorable tolerability profile was reported by 93.67% of the patients for troxipide and 64.55% for ranitidine.

Folinic acid has dextro- and levorotary isomers. Both levoleucovorin (the levorotary isomer) and racemic folinic acid (a mixture of both isomers) have similar efficacy and tolerability. Levoleucovorin was approved by the FDA in 2008.

Pegylation of interferon enhanced its half-life at the same time leading to increase of sustained virological response and reducing injection frequency. Because of the relatively low efficacy and tolerability of interferon and ribavirin, intense investigations in the development of direct acting antivirals were undertaken. Expression of direct acting antivirals does not occur in uninfected cells, therefore, improving its tolerability and efficacy in most genotypes of hepatitis C, up to 90%. 2011 – The first direct acting antiviral or NS3/4A (protease inhibitor) boceprevir was approved.

The noise standard in Germany for mentally stressful tasks is set at 55 dB(A), however, if the noise source is continuous, the threshold level for tolerability among office workers is lower than 55 dB(A).

The first Phase 1b trial (NCT02056808) began on November 2013 and involved 12 patients aged 5–11 years old. The patients were divided into three groups given escalating oral doses testing the safety and tolerability after each increase over the course of 10 days. Another completed Phase 1b trial (NCT02383511) began February 2015 and involved 12 patients aged 5–13 years old. The goal was to determine the safety, tolerability, and pharmacokinetic parameters by measuring plasma concentration and major metabolite levels over 28 days for three sequence groups.

A previous study had measured the safety and tolerability of tenofovir in both sexually active and abstinent women. This study gave support to the idea that tenofovir was a drug which was worth examining as an HIV preventative.

An open-label clinical study for infantile neuroaxonal dystrophy evaluating long-term evaluation of efficacy, safety, tolerability, and pharmacokinetics of RT001, which, when taken with food, can protect the neuronal cells from degeneration, started in the Summer 2018.

The levorotatory enantiomer of ketoconazole, levoketoconazole, shows 12-fold reduced potency in inhibition of this enzyme, and is under development for certain indications (e.g., Cushing's syndrome) as a replacement for ketoconazole with reduced toxicity and improved tolerability and safety.

Tolerability of zibotentan plus docetaxel has been evaluated. Zibotentan has also been studied in clinical trials for treatment of breast cancer, colorectal cancer, non-small cell lung cancer, ovarian cancer, scleroderma-related renal disease, bone metastasis, and heart failure.

The cephalosporins are diverse in their antibacterial spectrum, water solubility, acid tolerability, oral bioavailability, biological half-life and other properties. Therefore, the cephalosporins can be further classified into generations depending on antibacterial activity, time of invention and structural basis.

In partnership with University of Sydney, NSW Government, Chris O’Brien Lifehouse, Tilray participated in a clinical trial testing the efficacy and tolerability of medical cannabis as treatment for chemotherapy induced nausea & vomiting. Led by The Hospital for Sick Children, in Toronto, Canada, Tilray provided 2:100, the highest concentration of Cannabidiol (CBD) available in Canada, to test the efficacy and tolerability of medical cannabis oil as treatment for pediatric epilepsy/dravet syndrome. The study showed favourable results. In partnership with the University of British Columbia, Tilray provided medical cannabis products used to test medical cannabis as treatment for post-traumatic stress disorder.

A proof-of-concept study, reported by the University of Gießen Lung Center, was the first small study (in 4 PAH patients) to investigate safety, tolerability, pharmacokinetics and efficacy parameters. The drug was well tolerated and superior to NO in efficacy and duration. An open-label, non-controlled phase II trial of riociguat in 75 adult patients (42 with CTEPH and 33 with PAH, all in World Health Organization (WHO) functional class II or III) evaluated the safety and tolerability, and the effects on hemodynamics, exercise capacity and functional class. Riociguat was given three times daily for 12 weeks.

At week 12 of treatment, 75%, 90%, and 100% decreases in the Psoriasis Area and Severity Index (PASI) were achieved by 87%, 58%, and 16% of risankizumab treated patients, regardless of dose, respectively, versus individuals receiving placebo. Significant correlation between treatment-associated molecular changes and PASI improvement was observed in the risankizumab treated patients. The efficacy, safety and tolerability was further investigated in a phase III program comprising four clinical trials which compared risankizumab to ustekinumab, adalimumab and placebo in the indication of plaque psoriasis. The results of these trials confirmed the efficacy and tolerability of risankizumab.

A systematic review and meta-analysis of 5 studies found that N-Acetylcysteine reduces depressive symptoms more than placebo and has good tolerability. N-Acetylecysteine may exert benefits as a precursor to the antioxidant glutathione, thus modulating glutamatergic, neurotropic, and inflammatory pathways.

Racecadotril is used for the treatment of acute diarrhea in children and adults and has better tolerability than loperamide, as it causes less constipation and flatulence. Several guidelines have recommended racecadotril use in addition to oral rehydration treatment in children with acute diarrhea.

Over the past two decades, second- generation antidepressants have simply replaced first-generation antidepressants, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), as the drugs of choice for the treatment of MDD due to their improved tolerability and safety profile.

TCAs do not block dopamine transport directly but might facilitate dopaminergic effects indirectly by inhibiting dopamine transport into noradrenergic terminals of the cerebral cortex. Because they affect so many different receptors, TCAs have adverse effects, poor tolerability, and an increased risk of toxicity.

Patients with rheumatoid arthritis often need a long term, coordinated and a multidisciplinary team approach towards management of individual patients. Treatment is often tailored according to the individual needs of each patient which is also dependent on the response and the tolerability of medications.

After two years of attempts to obtain more stable semisynthetic products, a new molecule with high efficacy and good tolerability was produced in 1965 and was named "rifampicin". Rifampicin was first sold in Italy in 1968 and was approved by the FDA in 1971.

In June 2017 Westphal stepped down as CEO. In June 2018 the company halted clinical development of the drug candidate due to tolerability issues, cut its workforce, and said it was considering its strategy. In July 2018 MacKinnon resigned from the board of directors.

A 2018 analysis of 21 antidepressants found them to be fairly similar overall. It found tentative evidence for mirtazapine being in the more effective group and middle in tolerability. After one week of usage, mirtazapine was found to have an earlier onset of action compared to SSRIs.

Ketoconazole is a synthetic imidazole. It is a nonsteroidal compound. It is a racemic mixture of two enantiomers, levoketoconazole ((2S,4R)-(−)-ketoconazole) and dextroketoconazole ((2R,4S)-(+)-ketoconazole). Levoketoconazole is under development for potential clinical use as a steroidogenesis inhibitor with better tolerability and less toxicity than ketoconazole.

The drug combination aliskiren/amlodipine (INNs, trade names Tekamlo and Rasilamlo) is an antihypertensive. Clinical trials have shown it to be more effective than amlodipine on its own, with a high dosing regime (aliskiren 300 mg/amlodipine 10 mg) being more effective than olmesartan/amlodipine with comparable tolerability.

Brain function will be measured using EEG > both at rest and while participants are actively involved in those tests. > Importantly, this study will also evaluate the safety and tolerability of > repeated microdoses of LSD, via measures of LSD pharmacokinetics and > pharmacodynamics, including physiological markers of inflammation and > neurogenesis.

In 2016, the company launched "HotShot" as a dietary supplement for endurance athletes. In June 2018 the company halted clinical development of the drug candidate due to tolerability issues, cut its workforce, and said it was considering its strategy. In July 2018 MacKinnon resigned from the board of directors.

Brain function will be measured using EEG > both at rest and while participants are actively involved in those tests. > Importantly, this study will also evaluate the safety and tolerability of > repeated microdoses of LSD, via measures of LSD pharmacokinetics and > pharmacodynamics, including physiological markers of inflammation and > neurogenesis.

Amélie Gillette is an American newspaper columnist and television writer. She wrote the weekly infographic "The Tolerability Index" for The A.V. Club for 10 years and was a writer for the US version of The Office. She has written for many publications, including Spin, The Believer, and Blender.

It showed signs of efficacy in the form of prostatic specific antigen (PSA) decreases (4–29%) predominantly at higher doses (≥1,280 mg) in some patients but also caused side effects and was discontinued by its developer in favor of next-generation AR NTD inhibitors with improved potency and tolerability.

Meclofenoxate is considered to be very safe and high in tolerability. However, possible side effects may include, rarely, insomnia, dizziness, restlessness, muscle tremor, depression, nausea, muscle tension, and headache; these side effects may be due to overdosage and may indicate the need for the dosage to be reduced.

In a pooled analysis of 7 comparative trials with imipramine, milnacipran and imipramine were shown to have comparable efficacy while milnacipran was significantly better tolerated. A pooled analysis of studies comparing milnacipran and SSRIs concluded a superior efficacy for milnacipran with similar tolerability for milnacipran and SSRIs. A more recent meta-analysis of 6 studies involving more than 1,000 patients showed no distinction between milnacipran and SSRIs in efficacy or discontinuation rates, including discontinuation for side effects or lack of efficacy. A meta- analysis of a total of 16 randomized controlled trials with more than 2200 patients concluded that there were no statistically significant differences in efficacy, acceptability and tolerability when comparing milnacipran with other antidepressant agents.

The goal of the HEPACIVAC project is to develop HCV vaccines both at the pre-clinical level by testing safety, tolerability and immunogenicity, and at the clinical level by testing in healthy volunteers for safety and dose optimization and in chronically infected patients with and without the gold standard therapy.

In phase ΙΙ clinical studies to investigate safety, tolerability of gavestinel, no findings showed that it had significant side effects. The dose determined in phase ΙΙ trials was selected for further phase III trials. Later, however, in two large phase III trials, gavestinel showed no efficacy in treating ischemic stroke.

A short hypnotic medication has been effective to reduce insomnia related to jet lag.Suhner, A., Schlagenhauf, P., Höfer, I., Johnson, R., Tschopp, A., Steffen, R. (2001). Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag. Aviat Space Environ Med, 72:638–46.Reilly, T., Atkinson, G., Budgett, R. (2001).

Since JAK3 is not as ubiquitously expressed, selective targeting could improve tolerability, and decrease possible adverse effects and safety concerns. For example, dual inhibition of JAK1 and JAK3 might increase bacterial and viral infection because of a broader immunosuppressive effect. Inhibition of JAK2 has been linked to adverse effects such as anaemia and generalised leukopenia.

As well as evaluating safety and tolerability the study will investigate mechanisms of action and clinical endpoints. It is planned to complete by Feb 2018. The contract research organization working with GSK is PAREXEL, which will conduct the study at its site at Northwick Park Hospital in London. This trial started recruitment in early 2015.

Godin, B., Touitou, E. (2005) Erythromycin Ethosomal Systems: Physicochemical Characterization and Enhanced Antibacterial Activity. Cur. Drug Deliv., 2: 269-275.Touitou, E., Godin, B., Shumilov, M., Bishouty, N., Ainbinder, D., Shouval, R., Ingber, A., Leibovici, V. (2007) Efficacy and tolerability of clindamycin phosphate and salicylic acid gel in the treatment of mild to moderate acne vulgaris.

Acting through DP2, PGD2 can inhibit hair growth, suggesting that this receptor is a potential target for bald treatment. A phase 2A study to evaluate the safety, tolerability, and efficacy of oral setipiprant relative to a placebo in 18- to 49-year-old males with androgenetic alopecia was completed in May 2018 but no results have been published.

Antidepressants are recommended as an alternative or additional first step to self-help programs in the treatment of bulimia nervosa. SSRIs (fluoxetine in particular) are preferred over other anti-depressants due to their acceptability, tolerability, and superior reduction of symptoms in short-term trials. Long- term efficacy remains poorly characterized. Similar recommendations apply to binge eating disorder.

As gefitinib is a selective chemotherapeutic agent, its tolerability profile is better than previous cytotoxic agents. Adverse drug reactions (ADRs) are acceptable for a potentially fatal disease. Acne-like rash is reported very commonly. Other common adverse effects (≥1% of patients) include: diarrhoea, nausea, vomiting, anorexia, stomatitis, dehydration, skin reactions, paronychia, asymptomatic elevations of liver enzymes, asthenia, conjunctivitis, blepharitis.

In preclinical studies, the compound was shown to interact selectively with the thrombopoietin receptor, leading to activation of the JAK-STAT signaling pathway and increased proliferation and differentiation of megakaryocytes. Animal studies confirmed that it increased platelet counts. In 73 healthy volunteers, higher doses of eltrombopag caused larger increases in the number of circulating platelets without tolerability problems.

Flutamide was first described in 1967 and was first introduced for medical use in 1983. It became available in the United States in 1989. The medication has largely been replaced by newer and improved NSAAs, namely bicalutamide and enzalutamide, due to their better efficacy, tolerability, safety, and dosing frequency (once per day), and is now relatively little-used.

Selective serotonin reuptake inhibitors (SSRIs) selectively inhibit the reuptake of serotonin and are a widely used group of antidepressants. With increased receptor selectivity compared to TCAs, undesired effects such as poor tolerability are avoided. Serotonin is synthesized from an amino acid called L-tryptophan. Active transport system regulates the uptake of tryptophan across the blood–brain barrier.

Tilidine is rapidly absorbed after oral administration and is subject to a pronounced first-pass effect. The conversion of tilidine into the more active metabolite nortilidine occurs with the participation of CYP3A4 and CYP2C19. The inhibition of these enzymes can thus alter the efficacy and tolerability profile of tilidine. The analgesic effect occurs after 10-15 minutes.

Common side effects (in about 1–10% of patients) include gastrointestinal problems typical of NSAIDs, such as nausea, diarrhoea, stomach pain, and peptic ulcer; central nervous effects like headache and dizziness; and skin reactions. Gastrointestinal tolerability is better than that of the related drug indometacin. Severe allergic reactions and haematopoietic disorders occur in fewer than 0.01% of patients.

Infrequent adverse effects include urinary retention, palpitations, hypotension, headache, hallucination, and psychosis. The newer, second- generation H1-antihistamines are far more selective for peripheral histamine H1-receptors and have a better tolerability profile compared to the first- generation agents. The most common adverse effects noted for second-generation agents include drowsiness, fatigue, headache, nausea and dry mouth.

The company founded by Elio Bracco was established in 1927 in Milan with the name Società Italiana Prodotti E Merck, to produce, package and sell the chemical products of the German company E. Merck. It had just five employees. In 1934 Fulvio Bracco, Elio’s son, officially joined the company which, the same year, began marketing Cebion, an innovative product based on vitamin C, recently discovered by Hungarian professor Szent-Györgyi. In 1962 Bracco researchers created the first contrast agent based on their original research: iodamide, a product with very high tolerability. On 17 March 1977 Diana Bracco, Fulvio’s daughter, was appointed Bracco General Manager. In 1981 the company launched Iopamidol in Italy and Germany, a product with outstanding tolerability, whose stability allowed it to be stored in phials for unlimited periods of time.

Synaffix is a biotechnology company headquartered in the Netherlands that has developed a clinical-stage platform technology for antibody-drug conjugates (ADCs) which are used primarily in the treatment of cancer. ADCs utilize potent small molecule payloads, similar to those used for chemotherapy, but are designed to target only the cancer cells and spare normal, healthy tissues. The proprietary technology of Synaffix was developed to enable the treatment of a wide variety of cancer types and is designed to significantly enhance the effectiveness while also improving the safety and tolerability of these targeted cancer therapeutics. Benchmarking studies consistently demonstrate that, with a given antibody and ADC payload, ADCs produced using Synaffix technology display significantly enhanced effectiveness and significantly enhanced tolerability and safety versus all 3-major clinical- stage ADC technologies.

A 2012 clinical trial compared tocolytic efficacy and tolerability of atosiban with that of nifedipine. Forty-eight (68.6%) women allocated to atosiban and 39 (52%) to nifedipine did not deliver and did not require an alternate agent at 48 hours, respectively (p=.03). Atosiban has fewer failures within 48 hours. Nifedipine may be associated with a longer postponement of delivery.

The particle size of MPA crystals significantly influences its rate of absorption into the body from the local tissue depot when used as a microcrystalline aqueous suspension via intramuscular injection. Smaller crystals dissolve faster and are absorbed more rapidly, resulting in a shorter duration of action. Particle sizes can differ between different formulations of MPA, potentially influencing clinical efficacy and tolerability.

A long-term study found that there was no statistically significant difference in the time to discontinuation of use due to lack of tolerability between patients using LY-2140023 and other antipsychotic medications. Mild weight loss has also been associated with LY-2140023. In patients receiving 40 mg twice daily, a 0.51 kg weight reduction was observed after 4 weeks of treatment.

Methylphenobarbital (INN), also known as mephobarbital (USAN, JAN) and mephobarbitone (BAN), marketed under brand names such as Mebaral, Mephyltaletten, Phemiton, and Prominal, is a drug which is a barbiturate derivative and is used primarily as an anticonvulsant, but also as a sedative and anxiolytic. It is the N-methylated analogue of phenobarbital and has similar indications, therapeutic value, and tolerability.

In July 2001, Dr Tan Chong Kee, the founder of Sintercom, was asked to register the website under the nascent Singapore Broadcast Authority Act (now Media Development Authority). Dr Tan chose to shut down Sintercom due to concerns over the ambiguity of the Act.Tan Chong Kee. 'The Canary and the Crow: Sintercom and the State Tolerability Index' in Kenneth Paul Tan ed.

The efficacy and tolerability of almotriptan has been studied in numerous randomised, controlled trials totaling more than 4800 adults with either moderate or severe attacks of migraine. Its efficacy is significantly more effective than placebo and alleviates nausea, photophobia and phonophobia linked to migraine attacks. Almotriptan has similar efficacy as a standard dose of sumatriptan, another triptan drug, and fewer adverse effects.

Coadministration of brivaracetam with carbamazepine may increase exposure to carbamazepine-epoxide, the active metabolite of carbamazepine, and could theoretically lead to reduced tolerability. Coadministration of brivaracetam with phenytoin may increase phenytoin levels. Coadministration of other antiseizure drugs are unlikely to affect brivaracetam exposure. Brivaracetam provides no added therapeutic benefit when administered in conjunction with levetiracetam that acts on the same protein.

Acting through DP2, PGD2 can inhibit hair growth, suggesting that this receptor is a potential target for bald treatment. A potential drug for blocking the DP2 receptor and thereby ameliorating baldness is the compound setipiprant. A phase 2A study is underway to evaluate the safety, tolerability, and efficacy of oral setipiprant relative to a placebo in 18- to 49-year-old males with androgenetic alopecia.

Based on its exceptionally high, unequaled (among antipsychotics) affinity for the 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors, and very high affinity for the α2 and H1 receptors, asenapine, given normal tolerability, should theoretically demonstrate among the highest improvements in the negative symptomology of schizophrenia among all current antipsychotics (August 2017), such as high cognitive improvements and positive, stable mood maintenance.

High- dose estrogen therapy is used in the treatment of prostate cancer. Estrogens that have been used include diethylstilbestrol, fosfestrol, ethinylestradiol, ethinylestradiol sulfonate, polyestradiol phosphate, and estradiol undecylate, as well as the dual estrogenic and cytostatic agent estramustine phosphate. Newer estrogens with improved tolerability and safety like GTx-758 have also been studied. Estrogens are effective in prostate cancer because they are functional antiandrogens.

Within one review prulifloxacin was stated to have a similar tolerability profile to that of ciprofloxacin. Within another study it was found that prulifloxacin patients experienced a similar number of adverse reactions compared to those in the ciprofloxacin group (15.4% vs 12.7%). There were four serious adverse events in each treatment arm, including 1 death in the prulifloxacin arm. None were considered treatment related by the investigator.

The trial with Okairos vaccine candidate on naïve patients is in progress. The study started in November 2009. To date 23 patients have been enrolled. The primary objective of the trial is to test the safety, tolerability and immunogenicity of the heterologous prime-boost HCV vaccine candidate, when administered alone or in combination with the SOC therapy (pegylated-interferon and ribavirin – PEG-IFN/RBV).

Some of the side effects of CPA can be improved or fully prevented if it is combined with an estrogen to prevent estrogen deficiency. Few quantitative data are available on many of the potential side effects of CPA. Pooled tolerability data for CPA is not available in the literature. At very high doses in aged men with prostate cancer, CPA can cause cardiovascular side effects.

A sham injection will be administered to the other eye for comparison. It is hypothesized that introduction of the viral vector may be able to rescue the function of the mutant gene. Preliminary results have demonstrated tolerability of the injections in a small number of subjects. Stealth BioTherapeutics is presently investigating the potential use of elamipretide (MTP-131), a mitochondrial protective agent, as a therapy for LHON.

Low efficacy, serious side effects, development of resistance of previously available hepatitis C treatments were the greatest concerns prior to the development of direct acting antivirals, and remained a problem at the beginning of their development. Therefore, combinational direct acting antiviral therapies were preferable. Research has demonstrated that specific anti-hepatitis C virus agents such as NS5B inhibitors lead to improved efficacy and tolerability.

Antidepressants are recommended as an alternative or additional first step to self-help programs in the treatment of bulimia nervosa. SSRIs (fluoxetine in particular) are preferred over other antidepressants due to their acceptability, tolerability, and superior reduction of symptoms in short-term trials. Long-term efficacy remains poorly characterized. Bupropion is not recommended for the treatment of eating disorders due to an increased risk of seizure.

It has better tolerability than loperamide, as it causes less constipation and flatulence. However, it has little benefit in improving acute diarrhea in children. Bile acid sequestrants such as cholestyramine can be effective in chronic diarrhea due to bile acid malabsorption. Therapeutic trials of these drugs are indicated in chronic diarrhea if bile acid malabsorption cannot be diagnosed with a specific test, such as SeHCAT retention.

PVRIG is a novel B7/CD28-like immune checkpoint target candidate. In June 2016, Compugen announced the selection of COM701 as the lead therapeutic candidate for PVRIG. COM701 is currently being evaluated in a Phase 1 study in patients with advanced solid tumors. The study is designed to evaluate the safety and tolerability of COM701 as monotherapy and in combination with a PD-1 inhibitor.

"Dose, Efficacy and Tolerability of Long-term Indomethacin Treatment of Chronic Paroxysmal Hemicrania and Hemicrania Continua." Cephalalgia 21.9 (2001): 906-10. Print. Almost all cases of CPH respond positively and effectively to indometacin, but as much as 25 percent of patients discontinued use of the drug due to adverse side effects, namely complications in the gastrointestinal tract. Camarda, Cecilia, Rosolino Camarda, and Roberto Monastero.

Pimavanserin was developed by Acadia Pharmaceuticals. Pimavanserin is expected to improve the effectiveness and side effect profile of antipsychotics. The results of a clinical trial examining the efficacy, tolerability and safety of adjunctive pimavanserin to risperidone and haloperidol were published in November 2012, and the results showed that pimavanserin potentiated the antipsychotic effects of subtherapeutic doses of risperidone and improved the tolerability of haloperidol treatment by reducing the incidence of extrapyramidal symptoms. The drug met expectations for a Phase III clinical trial for the treatment of Parkinson's disease psychosis, and has completed Phase II trials for adjunctive treatment of schizophrenia alongside an antipsychotic medication. On September 2, 2014, the United States Food and Drug Administration granted Breakthrough Therapy status to Acadia's New Drug Application for pimavanserin. FDA Approval On April 29, 2016 Nuplazid (pimavanserin) was approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.

Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic. It is a dopamine D2 receptor partial agonist and has been described as a "serotonin–dopamine activity modulator" (SDAM). The drug was approved by the U.S. Food and Drug Administration (FDA) on July 10, 2015, for the treatment of schizophrenia, and as an adjunctive treatment for depression. It has been designed to provide improved efficacy and tolerability (e.g.

It is a subgroup of the macrolide antibiotics, and exhibits similar structural elements. Currently, the drug is available in many forms. Either "conventionally" complexed with sodium deoxycholate (ABD), as a cholesteryl sulfate complex (ABCD), as a lipid complex (ABLC), and as a liposomal formulation (LAMB). The latter formulations have been developed to improve tolerability and decrease toxicity, but may show considerably different pharmacokinetic characteristics compared to conventional amphotericin B.

After a minimum of 4 weeks at 16 mg/day, the treatment may be increased to 12 mg given twice a day (24 mg/day). Dosage increases are based upon the assessment of clinical benefit as well as tolerability of the previous dosage. If treatment is interrupted for more than three days, the process is usually restarted, beginning at the starting dosage, and re-escalating to the current dose.

Duloxetine was approved for the treatment of major depression in 2004. While duloxetine has demonstrated improvement in depression-related symptoms compared to placebo, comparisons of duloxetine to other antidepressant medications have been less successful. A 2012 Cochrane Review did not find greater efficacy of duloxetine compared to SSRIs and newer antidepressants. Additionally, the review found evidence that duloxetine has increased side effects and reduced tolerability compared to other antidepressants.

Safety and tolerability of North American ginseng extract in the treatment of pediatric upper respiratory tract infection: a phase II randomized, controlled trial of 2 dosing schedules. Pediatrics 2008; 122:e402-10.Predy GN, Goel V, Lovlin R, Donner A, Stitt L, Basu TK. Efficacy of an extract of North American ginseng containing poly-furanosyl-pyranosyl-sacchardies for preventing upper respiratory tract infections: a randomized controlled trial. CMAJ. 2005;173:1043-1048.

As such, it may have improved and prolonged efficaciousness and greater tolerability in comparison to currently available opioid analgesics. As an agonist of the κ-opioid receptor, cebranopadol may have the capacity to produce psychotomimetic effects, dysphoria, and other adverse reactions at sufficiently high doses, a property which could potentially limit its practical clinical dosage range, but would likely reduce the occurrence of patients taking more than their prescribed dose.

Estetrol differs in various ways both from other natural estrogens like estradiol and from synthetic estrogens like ethinylestradiol, with implications for tolerability and safety. For instance, it appears to have minimal estrogenic effects in the breasts and liver. Due to its unique tissue-selective effects, estetrol has been described as a natural selective estrogen receptor modulator (SERM). Estetrol was first discovered in 1965, and basic research continued up until 1984.

A Lancet study published on June 28, 2017 carried out a review between October 29, 2014 and August 19, 2016 where 298 patients were randomly assigned to receive at least one of the following: one dose of placebo per day, one dose of deutetrabenazine 12 mg/day, one dose of deutetrabenazine 24 mg/day, or one dose of deutetrabenazine 36 mg/day. From baseline to week 12, the least- squares mean AIMS (Abnormal Involuntary Movement Scale) score improved by −3.3 points in the deutetrabenazine 36 mg/day group, −3.2 points in the 24 mg/day group, −2.1 points in the 12 mg/day group, and −1.4 points in the placebo group. Deutetrabenazine 24 mg/day and 36 mg/day provided a significant reduction in tardive dyskinesia, with favourable safety and tolerability. These findings suggest that dosing regimens could be individualized and tailored for patients on the basis of dyskinesia control and tolerability.

Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte problems, and remove toxins in those with kidney failure. Peritoneal dialysis has better outcomes than hemodialysis during the first couple of years. Other benefits include greater flexibility and better tolerability in those with significant heart disease.

By 1963, carbamazepine was marketed in most of Europe. It soon became clear that its efficacy in generalized tonic-clonic seizures was the same as phenytoin, that its ability to control partial seizures was superior, along with its tolerability. Sodium valproate was approved in France in 1967. Because the doses were so low (200–400 mg/day), it was viewed as a moderately effective anticonvulsant whose best quality was its nonsedating nature.

The comparative efficacy of duloxetine and established pain-relief medications for DPN is unclear. A systematic review noted that tricyclic antidepressants (imipramine and amitriptyline), traditional anticonvulsants and opioids have better efficacy than duloxetine. Duloxetine, tricyclic antidepressants and anticonvulsants have similar tolerability while the opioids caused more side effects. Another review in Prescrire International considered the moderate pain relief achieved with duloxetine to be clinically insignificant and the results of the clinical trials unconvincing.

This study investigated safety, tolerability, pharmacokinetics and the impact on pulmonary and systemic haemodynamics of single doses of 0.5 and 1 mg of riociguat in patients with PAH and stable treatment of sildenafil (20 mg thrice daily) in a non-randomized uncontrolled trial. The study showed potentially unfavorable safety signals with sildenafil plus riociguat and no evidence of a positive benefit/risk ratio. Therefore, the concomitant use of riociguat with phosphodiesterase-5 inhibitors is contraindicated.

Phenserine was introduced as an inhibitor of acetylcholinesterase (AChE) and demonstrated significant alleviation in numerous neuropathological manifestations, improving cognitive functions of the brain. The ameliorative mechanism involves both cholinergic and non-cholinergic pathways. The clinical translatable doses of phenserine show relatively high tolerability and rarely manifest severe adverse effects. With respect to overdosing of the drug (20 mg/kg), a few cholinergic adverse effects were reported, including nausea and tremor which are not life-threatening.

Serelaxin has undergone clinical trials in patients with acute heart failure, conducted by Novartis. Serelaxin has completed several clinical trials as a therapy for AHF. Phase I trials examined safety and tolerability, while phase II trials evaluated its haemodynamic effects and symptom relief. The Pre-RELAX-AHF phase II trial administered a dose of 30 µg/kg/day and showed a decrease in blood pressure, improved dyspnoea, and increased renal blood flow.

Broadly speaking, a risk assessment is the combined effort of: # identifying and analyzing potential (future) events that may negatively impact individuals, assets, and/or the environment (i.e. risk analysis); and # making judgments "on the tolerability of the risk on the basis of a risk analysis" while considering influencing factors (i.e. risk evaluation). Put in simpler terms, a risk assessment determines possible mishaps, their likelihood and consequences, and the tolerances for such events.

Low doses, such as 280 mg/day, have been found to have comparable effectiveness as higher doses but with improved tolerability and reduced toxicity. Doses of 140 mg/day have been described as a very low dosage. EMP has been used at doses of 240 to 450 mg/day intravenously. EMP and other estrogens such as polyestradiol phosphate and ethinylestradiol are far less costly than newer therapies such as GnRH modulators, abiraterone acetate, and enzalutamide.

A double-blind randomized intraindividual study of lidocaine versus prilocaine in tumescent anesthesia for liposuction revealed no differences in efficacy or tolerability, except that lidocaine had a slightly more rapid onset of action. A clinician reported favorably on the use of ropivacaine for slow-infusion tumescent anesthesia, where ropivacaine provided local anesthesia for about twice as long as lidocaine. Bupivicaine is not recommended by the American Academy of Dermatology due to a lack of data on its use.

Consuming that quantity of MCT oil caused abdominal cramps, diarrhea, and vomiting in some children. A figure of 45% is regarded as a balance between achieving good ketosis and minimising gastrointestinal complaints. The classical and modified MCT ketogenic diets are equally effective and differences in tolerability are not statistically significant. The MCT diet is less popular in the United States; MCT oil is more expensive than other dietary fats and is not covered by insurance companies.

By blocking 5-HT1A autoreceptors at doses that are selective for them over postsynaptic 5-HT1A receptors, pindolol may be able to disinhibit serotonin release and thereby improve the antidepressant effects of SSRIs. The results of augmentation therapy with pindolol have been encouraging in early studies of low quality. However, a 2015 systematic review and meta- analysis of five randomized controlled trials found no overall significant benefit. There were also no significant differences in tolerability or safety.

Compounds from a quinazoline series can be considered as conformationally restricted analogs of a biarylamide series. In terms of activity 5-isoquinoline was found the most active among and ranked in the order of 5-isoquinoline > 8-quinoline > 8-quinazoline > 8-isoquinoline ≥ cinnoline > phthalazine > quinoxaline > 5-quinoline e.g. AMG517 (fig. 8b), although it lacks any recognizable carbonyl motif it still potently blocks capsaicin, proton, and heat activation of TRPV1 in vitro and shows a good tolerability profile.

Antiviral drugs may reduce the severity and duration of shingles; however, they do not prevent postherpetic neuralgia. Of these drugs, aciclovir has been the standard treatment, but the newer drugs valaciclovir and famciclovir demonstrate similar or superior efficacy and good safety and tolerability. The drugs are used both for prevention (for example in people with HIV/AIDS) and as therapy during the acute phase. Complications in immunocompromised individuals with shingles may be reduced with intravenous aciclovir.

In 2017, the U.S. Food and Drug Administration accepted Sunovion's New Drug Application (NDA) for review for the treatment of ADHD; however, the NDA was ultimately rejected citing the need for additional studies to determine efficacy and tolerability. In July 2019, Sunovion’s NDA for the treatment of BED was accepted with an expected action date of May 2020. In May 2020, Sunovion halted its drug development program for dasotraline, withdrawing both NDAs for ADHD and BED.

Sofosbuvir, a highly potent inhibitor of the NS5B polymerase, is active across all genotype of hepatitis C virus. It has high efficacy in combination with several other drugs, like ledipasvir, either with or without peginterferon-alfa. It has many advantages due to its tolerability, high potency, high resistance barrier, low side effects and oral administration. Another advantage of sofosbuvir is the low rates of interactions with other drugs, as its metabolism does not go through the CYP3A4 pathway.

These trials are often conducted in a clinical trial clinic, where the subject can be observed by full-time staff. These clinical trial clinics are often run by contract research organization (CROs) who conduct these studies on behalf of pharmaceutical companies or other research investigators. The subject who receives the drug is usually observed until several half-lives of the drug have passed. This phase is designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug.

Inhibition of JAK3, then, could prove to be a powerful immunosuppressant. Since JAK3 is restricted to the immune system, while the other JAKs such as JAK1 are much more broadly expressed, selective targeting of JAK3 could decrease possible adverse effects and improve tolerability. As an immunosuppressant, JAK3 inhibitors could aid in autoimmune diseases such as rheumatoid arthritis, psoriasis, or other diseases where the immune system fails to distinguish self from nonself and starts attacking self cells.

Large-scale trials confirmed the effectiveness of lovastatin. Observed tolerability continued to be excellent, and lovastatin was approved by the US FDA in 1987.FDA Orange Book Detail for application N019643 showing approval for 20 mg tablets on Aug 31, 1987 and 40 mg tablets on Dec 14, 1988 It was the first statin approved by the FDA. Lovastatin is also naturally produced by certain higher fungi, such as Pleurotus ostreatus (oyster mushroom) and closely related Pleurotus spp.

These are the oldest H1-antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly potent muscarinic acetylcholine receptor (anticholinergic) antagonists as well. These agents also commonly have action at α-adrenergic receptors and/or 5-HT receptors. This lack of receptor selectivity is the basis of the poor tolerability profile of some of these agents, especially when compared with the second-generation H1-antihistamines.

Due to its risks, the use of flutamide in cisgender and transgender women is now limited and discouraged. Flutamide and nilutamide have largely been superseded by bicalutamide in clinical practice, with bicalutamide accounting for almost 90% of nonsteroidal antiandrogen prescriptions in the United States by the mid-2000s. Bicalutamide is said to have excellent tolerability and safety relative to flutamide and nilutamide, as well as in comparison to cyproterone acetate. It has few to no side effects in women.

When compared with benzodiazepines, nonbenzodiazepines (including zaleplon) offer few significant advantages in efficacy and tolerability among elderly individuals. Long-term use of sedative/hypnotics for insomnia has traditionally been discouraged for reasons that include concerns about addiction and rebound insomnia, as well to the risk of side effects associated to GABAA agonists, such as cognitive impairment, anterograde amnesia, daytime sedation, musculoskeletal impairment, and subsequently an increased risk of harm to oneself (e.g. falling) and to others (e.g. automotive accidents).

In addition, progesterone has antigonadotropic effects due to its progestogenic activity and can inhibit fertility and suppress sex hormone production. Progesterone differs from progestins (synthetic progestogens) like medroxyprogesterone acetate and norethisterone, with implications for pharmacodynamics and pharmacokinetics as well as efficacy, tolerability, and safety. Progesterone can be taken by mouth, in through the vagina, and by injection into muscle or fat, among other routes. A progesterone vaginal ring and progesterone intrauterine device are also available as pharmaceutical products.

In a small low-dose study using 280 mg/day oral EMP for 150 days, tolerability was significantly improved, with gastrointestinal irritation occurring in only 15% of men, and there was no incidence of severe cardiovascular toxicity or deep vein thrombosis. In addition, no other side effects besides slight transient elevated liver enzymes were observed. These findings suggest that lower doses of oral EMP may be a safer option than higher doses for the treatment of prostate cancer.

AMG 319 is a drug developed by Amgen which acts as an inhibitor of the phosphoinositide 3-kinase enzyme subtype PI3Kδ. It was originally developed as an anti-inflammatory drug with potential applications in the treatment of autoimmune conditions such as rheumatoid arthritis, but subsequent research showed that it inhibits cell proliferation and might potentially have useful anti-cancer effects, and it has been put into clinical trials to assess its safety and tolerability in this application.

In addition, progesterone has antigonadotropic effects due to its progestogenic activity and can inhibit fertility and suppress sex hormone production. Progesterone differs from progestins (synthetic progestogens) like medroxyprogesterone acetate and norethisterone, with implications for pharmacodynamics and pharmacokinetics as well as efficacy, tolerability, and safety. Progesterone can be taken by mouth, in through the vagina, and by injection into muscle or fat, among other routes. A progesterone vaginal ring and progesterone intrauterine device are also available as pharmaceutical products.

Physostigmine's poor tolerability led to it being abandoned in favor of later acetylcholinesterase inhibitors, three of which are currently in use: donepezil, galantamine, and rivastigmine. Recently, it has begun to be used in the treatment of orthostatic hypotension. Recently, physostigmine has been proposed as an antidote for intoxication with gamma hydroxybutyrate (GHB, a potent sedative- hypnotic agent that can cause loss of consciousness, loss of muscle control, and death). Physostigmine may counteract GHB by producing a nonspecific state of arousal.

Although phlorizin was not suitable for further clinical trials, it served an important role in the development of SGLT-2 inhibitors. It served a basis for the recognition of SGLT inhibitors with improved safety and tolerability profiles. For an example, the SGLT inhibitors are not associated with gastrointestinal adverse events and the bioavailability is much greater. Inhibition of SGLT-2 results as better control of glucose level, lower insulin, lower blood pressure and uric acid levels and augments calorie wasting.

No drug has been shown to be better than another, and all of them have adverse effects, particularly dizziness and drowsiness. Concerns about possible abuse and interaction with other drugs, especially if increased sedation is a risk, further limit their use. A muscle relaxant is chosen based on its adverse- effect profile, tolerability, and cost. Muscle relaxants (according to one study) were not advised for orthopedic conditions, but rather for neurological conditions such as spasticity in cerebral palsy and multiple sclerosis.

Lastly, galantamine may be oxidized and then reduced before finally undergoing demethylation or oxidation at its nitrogen atom, or demethylation and subsequent glucuronidation at its oxygen atom. Metabolic pathways of galantamine For Razadyne ER, the once-a-day formulation, CYP2D6 poor metabolizers had drug exposures that were approximately 50% higher than for extensive metabolizers. About 7% of the population has this genetic mutation; however, because the drug is individually titrated to tolerability, no specific dosage adjustment is necessary for this population.

MTH1 is a potential drug target to treat cancer, however there are conflicting results regarding the cytotoxicity of MTH1 inhibitors toward cancer cells. Karonudib, an MTH1 inhibitor, is currently being evaluated a phase I clinical trial for safety and tolerability. A potent and selective MTH1 inhibitor AZ13792138 has been developed by AstraZeneca has been made available as a chemical probe to academic researchers. However AstraZeneca has found that neither AZ13792138 nor genetic knockdown of MTH1 displays any significant cytotoxicity to cancer cells.

Few quantitative data are available on many of the potential side effects of CPA. Pooled tolerability data for CPA is not available in the literature. At very high doses in aged men with prostate cancer, CPA can cause cardiovascular side effects. Rarely, CPA can produce blood clots, liver toxicity (including hepatitis, liver failure, and liver cancer), excessively high prolactin levels, and certain benign brain tumors including meningiomas (tumors of the meninges) and prolactinomas (prolactin-secreting tumors of the pituitary gland).

Glaxo refined the model further, by replacing the imidazole ring of cimetidine with a furan ring with a nitrogen-containing substituent, and in doing so developed ranitidine. Ranitidine was found to have a far-improved tolerability profile (i.e. fewer adverse drug reactions), longer-lasting action, and 10 times the activity of cimetidine. Ranitidine has 10% of the affinity that cimetidine has to CYP450, so it causes fewer side effects, but other H2 blockers famotidine and nizatidine have no CYP450 significant interactions.

A randomized, double-blind, placebo-controlled phase I study to examine the safety and tolerability of asunercept has shown that it is well tolerated. The efficacy of asunercept was tested in a phase II randomized controlled trial with patients suffering from GBM. A total of 83 patients with first or second relapse of GBM were enrolled in the successful proof-of-concept trial. The primary goal of doubling the number of patients reaching progression-free survival at six months (PFS6) was substantially exceeded.

The environment is an important issue when approving Hermes guarantees. When appraising the application, the environmental effects of projects are an important criterion, both in terms of their worthiness and the tolerability of the risk. As stated by the ECA, it is the aim of the German government not to support any projects that have serious negative ecological, social, or developmental consequences. Since January 1, 2004, the OECD "Recommendation on Common Approaches on Environment and Officially Supported Export Credits" have been applied.

Current treatment options include phenytoin, valproic acid, ethosuximide, and the new anti-epileptic drugs. Over the past 20 years, 15 new anti-epileptic drugs with positive outcomes have been introduced to the public. These new AEDs are aimed at improving the cost-benefit balance in AED therapy, improving tolerability profiles and reducing potential for drug interaction. Despite these major advances, there is always room for improvement, especially regarding the tailored treatment of individuals who have suffered adverse effects from older AEDs.

It remained the "gold standard" for the treatment of OCD for many years until the introduction of the SSRIs, which have since largely superseded it due to greatly improved tolerability and safety (although notably not effectiveness). Clomipramine is the only TCA that has been shown to be effective in the treatment of OCD and that is approved by the FDA for the treatment of OCD; the other TCAs failed clinical trials for this indication, likely due to insufficient serotonergic activity.

In 1894, he joined Bayer as a research chemist. On 10 August 1897 Hoffmann synthesized acetylsalicylic acid (ASA) while working at Bayer under Arthur Eichengrün. By combining salicylic acid with acetic acid, he succeeded in creating ASA in a chemically pure and stable form. The pharmacologist responsible for verifying these results was skeptical at first, yet once several large-scale studies to investigate the substance's efficacy and tolerability had been completed, it was found to be an analgesic, antipyretic and antiinflammatory substance.

Zopiclone increases postural sway and increases the number of falls in older people, as well as cognitive side effects. Falls are a significant cause of death in older people. An extensive review of the medical literature regarding the management of insomnia and the elderly found that considerable evidence of the effectiveness and lasting benefits of nondrug treatments for insomnia exist. Compared with the benzodiazepines, the nonbenzodiazepine sedative-hypnotics, such as zopiclone, offer few if any advantages in efficacy or tolerability in elderly persons.

The phase I, open-label, dose-ranging study of 40 healthy adult volunteers is evaluating the safety, tolerability and immunogenicity of GLS-5700 administered with the CELLECTRA®-3P device, Inovio's proprietary intradermal DNA delivery device. In preclinical testing, this synthetic vaccine induced robust antibody and T cell responses – the immune responses necessary to fight viral infections – in small and large animal models. Direct Relief, an emergency response organization, established a Zika Fund and fulfilled requests for supplies in 14 affected countries.

In early 2018, a Phase 1 clinical trial of mAb114's safety, tolerability and pharmacokinetics was conducted by Dr. Martin Gaudinski within the Vaccine Research Center Clinical Trials Program that is led by Dr. Julie E. Ledgerwood. The study was performed in the United States at the NIH Clinical Center and tested single dose infusions of mAb114 infused over 30 minutes. The study showed that mAb114 was safe, had minimal side effects and had a half-life of 24 days.

An erythematous rash in sun-exposed parts of the body has been reported to occur in 7.3–21.2% of persons taking doxycycline for malaria prophylaxis. One study examined the tolerability of various malaria prophylactic regimens and found doxycycline did not cause a significantly higher percentage of all skin events (photosensitivity not specified) when compared with other antimalarials. The rash resolves upon discontinuation of the drug. Unlike some other members of the tetracycline group, it may be used in those with renal impairment.

Progesterone lowers blood pressure and reduces water and salt retention among other effects via its antimineralocorticoid activity. In addition, progesterone can produce sedative, hypnotic, anxiolytic, euphoric, cognitive-, memory-, and motor-impairing, anticonvulsant, and even anesthetic effects via formation of sufficiently high concentrations of its neurosteroid metabolites and consequent GABAA receptor potentiation in the brain. There are differences between progesterone and progestins, such as medroxyprogesterone acetate and norethisterone, with implications for pharmacodynamics and pharmacokinetics, as well as for efficacy, tolerability, and safety.

Between 2010 to 2011, a safety and tolerability Phase I/II study (IPM-015) of Ring-004 was conducted in Kenya, Malawi, South Africa, and Tanzania. A sampling pool of 280 African women aged 18 to 40 were involved. The device was reported to be safe and well-accepted by wearers throughout the continuous 12-week utilisation period. However, a few reports of mild adverse effects caused by the ring were mentioned such as pelvic abnormalities, vaginal discharge, intermenstrual bleeding.

Ebastine has shown overall safety and tolerability profile with no cognitive/psychomotor impairment and no sedation worse than placebo, and cardiac safety, that is, no QT prolongation. The incidence of most commonly reported adverse events was comparable between the ebastine and placebo groups, which confirms that ebastine has a favourable safety profile. While experiments in pregnant animals showed no risk for the unborn, no such data are available in humans. It is not known whether ebastine passes into the breast milk.

Hydroxyzine is used in the treatment of itchiness, anxiety, and nausea due to motion sickness. A systematic review concluded that compared with other anxiolytic agents (benzodiazepines and buspirone), hydroxyzine was equivalent in efficacy, acceptability, and tolerability. Hydroxyzine can also be used for the treatment of allergic conditions, such as chronic urticaria, atopic or contact dermatoses, and histamine-mediated pruritus. These have also been confirmed in both recent and past studies to have no adverse effects on the liver, blood, nervous system, or urinary tract.

Flesinoxan (DU-29,373) is a potent and selective 5-HT1A receptor partial/near- full agonist of the phenylpiperazine class. Originally developed as a potential antihypertensive drug, flesinoxan was later found to possess antidepressant and anxiolytic effects in animal tests. As a result, it was investigated in several small human pilot studies for the treatment of major depressive disorder, and was found to have robust effectiveness and very good tolerability. However, due to "management decisions", the development of flesinoxan was stopped and it was not pursued any further.

Gastrointestinal upset can cause severe discomfort; it is most common when metformin is first administered, or when the dose is increased. The discomfort can often be avoided by beginning at a low dose (1.0 to 1.7 grams per day) and increasing the dose gradually, but even with low doses, 5% of people may be unable to tolerate metformin. Use of slow- or extended-release preparations may improve tolerability. Long-term use of metformin has been associated with increased homocysteine levels and malabsorption of vitamin B12.

Results demonstrated a statistically significant improvement with solabegron as compared with placebo, as measured by the percentage reduction of the number of wet episodes and the absolute number of daily voids. A Phase II study for irritable bowel syndrome (IBS) evaluated 102 patients with IBS. Solabegron demonstrated significant reduction in pain associated with the disorder and a trend for greater improvement in the quality of life, when compared with a placebo. Both Phase II studies indicated a tolerability profile for solabegron that was similar to placebo.

Blonanserin, sold under the brand name Lonasen, is a relatively new atypical antipsychotic (approved by PMDA in January 2008) commercialized by Dainippon Sumitomo Pharma in Japan and Korea for the treatment of schizophrenia. Relative to many other antipsychotics, blonanserin has an improved tolerability profile, lacking side effects such as extrapyramidal symptoms, excessive sedation, or hypotension. As with many second-generation (atypical) antipsychotics it is significantly more efficacious in the treatment of the negative symptoms of schizophrenia compared to first-generation (typical) antipsychotics such as haloperidol.

Estradiol should not be used in women who are pregnant or breastfeeding or who have breast cancer, among other contraindications. Estradiol is a naturally occurring and bioidentical estrogen, or an agonist of the estrogen receptor, the biological target of estrogens like endogenous estradiol. Due to its estrogenic activity, estradiol has antigonadotropic effects and can inhibit fertility and suppress sex hormone production in both women and men. Estradiol differs from non- bioidentical estrogens like conjugated estrogens and ethinylestradiol in various ways, with implications for tolerability and safety.

The trial is an open label, non-randomised study to determine the safety and tolerability of four doses of SCIB1 administered intramuscularly using an electroporation device (TDS-IM, manufactured by Ichor Medical Systems, USA). The study will also assess immune effects and anti-tumour activity in patients with melanoma. The trial is being conducted in patients with both unresected and resected disease. Patients with Stage III or Stage IV melanoma received up to five doses of the SCIB1 vaccine over a 6-month period.

Amitriptyline is used for a number of medical conditions including major depressive disorder (MDD). Some evidence suggests amitriptyline may be more effective than other antidepressants, including selective serotonin reuptake inhibitors (SSRIs), although it is rarely used as a first-line antidepressant due to its higher toxicity in overdose and generally poorer tolerability, so is used as a second-line treatment when SSRIs do not work. It is used in addition to other medications for pain. A 2001 review called it "the gold-standard antidepressant".

Agents currently under investigation include, antiglutamatergics, monoamine oxidase inhibitors (selegiline, rasagiline), promitochondrials (coenzyme Q10, creatine), calcium channel blockers (isradipine) and growth factors (GDNF). Reducing alpha- synuclein pathology is a major focus of preclinical research. A vaccine that primes the human immune system to destroy alpha-synuclein, PD01A (developed by Austrian company, Affiris), entered clinical trials and a phase 1 report in 2020 suggested safety and tolerability. In 2018, an antibody, PRX002/RG7935, showed preliminary safety evidence in stage I trials supporting continuation to stage II trials.

In women, HDE may cause amenorrhea and rarely endometrial hyperplasia or endometrial cancer, but the risk of adverse endometrial changes is minimized or offset with pseudopregnancy regimens due to the progestogen component. The tolerability profile of HDE is worse in men compared to women. Side effects of HDE specific to men may include gynecomastia (breast development), feminization and demasculinization in general (e.g., reduced body hair, decreased muscle mass and strength, feminine changes in fat mass and distribution, and reduced penile and testicular size), and sexual dysfunction (e.g.

MTN revealed at the International AIDS Conference 2016 in July that participants who had consistent use of the DPV ring had a 56% lower risk of HIV. However, women younger than 21 years old are less likely to adhere to the intravaginal HIV microbicide regimen. From 2016 to 2018, Phase III/IIIb open-label clinical trials HOPE (MTN-025) and DREAM (IPM-032) were launched to focus on the safety and tolerability of the tool on a monthly basis. These trials included participants across South Africa.

The pharmacology of estradiol, an estrogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration. Estradiol is a naturally occurring and bioidentical estrogen, or an agonist of the estrogen receptor, the biological target of estrogens like endogenous estradiol. Due to its estrogenic activity, estradiol has antigonadotropic effects and can inhibit fertility and suppress sex hormone production in both women and men. Estradiol differs from non- bioidentical estrogens like conjugated estrogens and ethinylestradiol in various ways, with implications for tolerability and safety.

The efficacy and tolerability of a fixed-dose combination of 4 mg perindopril and 5 mg amlodipine, a calcium channel antagonist, has been confirmed in a prospective, observational multicenter trial of 1,250 hypertensive patients.Bahl VK, Jadhav UM, Thacker HP. Management of Hypertension with the Fixed Combination of Perindopril and Amlodipine in Daily Clinical Practice: Results from the STRONG Prospective, Observational, Multicenter Study. American Journal of Cardiovascular Drugs May 22, 2009; 9 (3): 135-42 Link text A preparation of the two drugs is available commercially as Coveram.

Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, are the first choice of medication for generalized social phobia but a second line treatment. Compared to older forms of medication, there is less risk of tolerability and drug dependency associated with SSRIs. Paroxetine and paroxetine CR, Sertraline, Escitalopram, Venlafaxine XR and Fluvoxamine CR (luvox CR) are all approved for SAD and are all effective for it especially paroxetine. All SSRIs are somewhat effective for social anxiety except fluoxetine which was equivalent to placebo in all clinical trials except one.

Nventa originally advanced HspE7 as a single-agent therapy into multiple Phase 2 clinical trials with positive results, including trials in cervical dysplasia and recurrent respiratory papillomatosis (RRP). These trials were initiated prior to the discovery that potency could be greatly enhanced by addition of a vaccine adjuvant.International HPV Conference Poster: “NVENTA PRESENTS HSPE7 DATA AT INTERNATIONAL HPV CONFERENCE” / Nventa Press Release, November 5, 2007 Nventa is currently developing HspE7 combined with the TH1-directed adjuvant Poly- ICLC. A Phase 1b study is complete, assessing safety and tolerability in 17 patients with CIN.

In order to improve the tolerability of amphotericin and reduce toxicity, several lipid formulations have been developed. Liposomal formulations have been found to have less renal toxicity than deoxycholate, and fewer infusion-related reactions. They are more expensive than amphotericin B deoxycholate. AmBisome (LAMB) is a liposomal formulation of amphotericin B for injection and consists of a mixture of phosphatidylcholine, cholesterol and distearoyl phosphatidylglycerol that in aqueous media spontaneously arrange into unilamellar vesicles that contain amphotericin B. It was developed by NeXstar Pharmaceuticals (acquired by Gilead Sciences in 1999).

The first two trials are safety and efficacy studies of abicipar in patients with wet AMD to establish comparability between Japanese and non-Japanese patients. The third study is to test the safety and efficacy of abicipar in patients with DME. In July 2014, Molecular Partners initiated a first-in-human study to investigate the safety, tolerability and blood levels of MP0250, a second DARPin candidate, in patients with cancer. Molecular Partners AG has several additional DARPins in preclinical development with potential indications in various disease areas, including ophthalmology, oncology, immuno-oncology and immunology.

In clinical trials, pherines formulated for intranasal administration in ultra low doses (nanogram to low microgram quantities) showed rapid onset of efficacy (10–15 minutes) and an excellent safety and tolerability profile. Pherines are also minimally invasive (do not require systemic absorption) to exert their pharmacological effects and can be used on demand Pherines described in the scientific literature include PH10, PH15, PH80, PH284 and PH94B (Aloradine, or 4,16-androstadien-3β-ol, a positional isomer of androstadienol). Pherines are chemically and pharmacologically different from natural pheromones including androstadienone, androstenone, androstenol, androsterone, and estratetraenol.

Even though cetalkonium chloride is belongs to the family of benzalkonium chloride, the ophthalmic use of cetalkonium chloride cationic nanoemulsions have been shown to be safe.Liang, H., F. Brignole-Baudouin, et al. (2008). "Reduction of quaternary ammonium-induced ocular surface toxicity by emulsions: an in vivo study in rabbits." Mol Vis 14: 204-16Amrane M, Creuzot-Garcher C, Robert PY, Ismail D, Garrigue JS, Pisella PJ, Baudouin C. Ocular tolerability and efficacy of a cationic emulsion in patients with mild to moderate dry eye disease - A randomised comparative study.

The EMA had previously granted it orphan status for the treatment of SMA. Reldesemtiv was evaluated during preclinical studies, five Phase 1 clinical trials, and two Phase 2 clinical trials. Cytokinetics had previously partnered with Astellas to share development costs for reldesemtiv, and in 2020 the agreement was changed, giving Cytokinetics exclusive control over the drug. Cytokinetics is developing CK-3773274 (CK-274), an oral, small-molecule myosin inhibitor, to treat hypertrophic cardiomyopathy (HCM). The drug’s Phase 1 trial, which assessed the safety and tolerability of single and multiple oral doses, started in December 2018.

Baclofen, a GABA-B receptor agonist and antispasmodic medication, has been found to reduce cravings but without a significant benefit towards preventing relapse or improving sleep. Zolpidem, a GABA-A receptor agonist and "Z-hypnotic" medication, has shown some efficacy in treating insomnia due to cannabis withdrawal, though there is a potential for misuse. Entacapone was well tolerated and decreased cannabis cravings in a trial on a small number of patients. Topiramate, an antiepileptic drug, has shown mixed results in adolescents, reducing the volume of cannabis consumption without significantly increasing abstinence, with somewhat poor tolerability.

Namilumab (alternative identifier MT203) is a human monoclonal antibody (class IgG1 kappa) that targets granulocyte macrophage-colon stimulating factor (GM- CSF)/colony stimulating factor 2 (CSF2) and is currently being researched for application in rheumatoid arthritis (RA) and psoriatic arthritis. Clinical trials investigating the therapeutic utility of Namilumab have include phase I and phase II clinical trials to establish the safety, tolerability and preliminary therapeutic utility of the antibody in plaque psoriasis and rheumatoid arthritis. Namilumab was produced by Micromet Inc and is under development by Takeda Pharmaceuticals International.

Glaxo refined the model further by replacing the imidazole-ring of cimetidine with a furan-ring with a nitrogen- containing substituent, and in doing so developed ranitidine, which was found to have a much better tolerability profile (i.e. fewer adverse drug reactions), longer-lasting action, and ten times the activity of cimetidine. Ranitidine was introduced in 1981 and was the world's biggest-selling prescription drug by 1988. The H2-receptor antagonists have since largely been superseded by the even more effective proton pump inhibitors (PPIs), with omeprazole becoming the biggest-selling drug for many years.

Throughout the 1960s and 1970s, the catecholamine hypothesis of emotion and its relation to depression was of wide interest and that the decreased levels of certain neurotransmitters, such as norepinephrine, serotonin, and dopamine might play a role in the pathogenesis of depression. This led to the development of fluoxetine, the first SSRI. The improved safety and tolerability profile of the SSRIs in patients with MDD, compared with TCAs and MAOIs, represented yet another important advance in the treatment of depression. Since the late 1980s, SSRIs have dominated the antidepressant drug market.

In 2008, two phase I clinical trials of paclitaxel trevatide were started; one in patients with advanced cancer and brain metastases, and another in patients with recurrent malignant glioma. Favorable initial tolerability results in brain cancer were reported in March 2009. and more in October 2009 and updated in June 2010. (paid subscription required) In 2014, paclitaxel trevatide received orphan drug designation from FDA for the treatment of glioblastoma multiform As of January 2016, Angiochem has conducted phase II trials for the treatment of breast cancer with brain metastasis, glioblastoma, and high-grade glioma.

There is promising evidence that a ketogenic diet (high-fat, low-carbohydrate, adequate-protein) decreases the number of seizures and eliminate seizures in some; however, further research is necessary. It is a reasonable option in those who have epilepsy that is not improved with medications and for whom surgery is not an option. About 10% stay on the diet for a few years due to issues of effectiveness and tolerability. Side effects include stomach and intestinal problems in 30%, and there are long-term concerns about heart disease.

Double-blind randomized controlled trials have demonstrated the efficacy and tolerability of modafinil in pediatric ADHD, however there are risks of serious side effects such as skin reactions and modafinil is not recommended for use in children. In the United States, it was originally pending marketing on-label as Sparlon, but approval was denied by the FDA due to major concerns over the occurrence of Stevens–Johnson syndrome in clinical trials. Other medications which may be prescribed off-label include certain antidepressants such as tricyclic antidepressants (TCAs), SNRIs, SSRIs, or MAOIs.

A proper regimen of antibiotics for perioperative prophylaxis of septic complications decreases the total amount of antimicrobials needed and eases the burden on hospitals. The choice of antibiotics should be made according to data on pharmacology, microbiology, clinical experience and economy. Drugs should be selected with a reasonable spectrum of activity against pathogens likely to be encountered, and antibiotics should be chosen with kinetics that will ensure adequate serum and tissue levels throughout the risk period. For prophylaxis in surgery, only antibiotics with good tolerability should be used.

Melitracen (brand names Melixeran) is a tricyclic antidepressant (TCA), for the treatment of depression and anxiety. In addition to single drug preparations, it is also available as Deanxit, marketed by Lundbeck, a combination product containing both melitracen and flupentixol. The pharmacology of melitracen has not been properly investigated and is largely unknown, but it is likely to act in a similar manner to other TCAs. Indeed, melitracen is reported to have imipramine and amitriptyline-like effects and efficacy against depression and anxiety, though with improved tolerability and a somewhat faster onset of action.

Aramchol is an investigational drug being developed by Galmed Pharmaceuticals as a first-in-class, potentially disease modifying treatment for nonalcoholic steatohepatitis, or NASH, a more advanced condition of non-alcoholic fatty liver disease. Aramchol, a conjugate of cholic acid and arachidic acid, is a member of a synthetic fatty-acid/bile-acid conjugate (FABAC). FABACs are composed of endogenous compounds, orally administrated with potentially good safety and tolerability parameters. Aramchol affects liver fat metabolism and has been shown in a Phase IIa clinical study to significantly reduce liver fat content as well as improve metabolic parameters associated with fatty liver disease.

Galantamine's side effect profile was similar to that of other cholinesterase inhibitors, with gastrointestinal symptoms being the most notable and most commonly observed. One study reports higher proportions of patients treated with galantamine experiencing nausea and vomiting as opposed to the placebo group. Another study using a dose- escalation treatment has found that incidences of nausea would decrease to baseline levels soon after each increase in administered dosage. In practice, some other cholinesterase inhibitors might be better tolerated; however, a careful and gradual titration over more than three months may lead to equivalent long-term tolerability.

It was previously used to treat symptoms of dyskinesia in patients suffering from Huntington's disease, but alternative medications are preferred today. The daily dose of reserpine in antihypertensive treatment is as low as 0.05 to 0.25 mg. The use of reserpine as an antipsychotic drug had been nearly completely abandoned, but more recently it made a comeback as adjunctive treatment, in combination with other antipsychotics, so that more refractory patients get dopamine blockade from the other antipsychotic, and dopamine depletion from reserpine. Doses for this kind of adjunctive goal can be kept low, resulting in better tolerability.

Oxcarbazepine is an anticonvulsant used to reduce the occurrence of epileptic episodes, and is not intended to cure epilepsy. Oxcarbazepine is used alone or in combination with other medications for the treatment of focal (partial) seizures in adults. In pediatric populations, it can be used by itself for the treatment of partial seizures for children 4 years and older, or in combination with other medications for children 2 years and older. A 2020 Cochrane review found that it was effective in reducing seizure frequency when used as an add-on therapy for drug-resistant focal epilepsy but there were concerns over tolerability.

In phase II clinical trials, the drug was used in combination with standard treatments, such as four or five of the drugs ethambutol, isoniazid, pyrazinamide, rifampicin, aminoglycoside antibiotics, and quinolones. Healing rates (measured as sputum culture conversion) were significantly better in patients who additionally took delamanid. The European Medicines Agency (EMA) recommended conditional marketing authorization for delamanid in adults with multidrug-resistant pulmonary tuberculosis without other treatment options because of resistance or tolerability. The EMA considered the data show that the benefits of delamanid outweigh the risks, but that additional studies were needed on the long-term effectiveness.

It is poorly absorbed into most cells, but is actively transported by folate receptor alpha (FRα), which is usually only expressed at low levels in the apical membrane of some specialised tissues, but is expressed at much higher levels in some subtypes of ovarian cancer. This causes the drug to accumulate selectively in tumour tissues, while healthy tissues are only exposed to a much lower concentration.Ng C, et al. Efficacy and tolerability of the thymidylate synthase (TS) inhibitor, BGC 945 is mediated through its selective uptake via the α-folate receptor (α-FR) in IGROV-1 human tumor xenografts.

Daytime withdrawal effects can occur. An extensive review of the medical literature regarding the management of insomnia and the elderly found considerable evidence of the effectiveness and durability of nondrug treatments for insomnia in adults of all ages and that these interventions are underused. Compared with the benzodiazepines including triazolam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. Newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people.

Ciclacillin (INN) or cyclacillin (USAN), trade names Cyclapen, Cyclapen-W, Vastcillin, and others, is an aminopenicillin antibiotic. Its spectrum of activity is similar to that of ampicillin, although it is less susceptible to beta-lactamases than ampicillin and has much higher bioavailability. A large randomized, double-blind clinical trial published in 1978 also showed that ciclacillin is associated with significantly fewer and milder adverse effects than ampicillin; later studies seemed to confirm this improved tolerability, at least in children. Ciclacillin has been superseded by newer antibiotics and is no longer in clinical use, at least in the United States.

A phase 1 clinical trial in 2004 demonstrated the safety and tolerability of mapatumumab in cancer patients with advanced solid tumors or non-Hodgkin’s lymphoma, and supported further evaluation in phase 2 clinical trials, both as a single agent and in combination with chemotherapy. In a phase 2 clinical trial, mapatumumab was well tolerated and could be administered safely in patients with advanced non-small-cell lung cancer (NSCLC) and advanced colorectal cancer. Stable disease was observed in a number of NSCLC patients. In two phase 1b clinical trials mapatumumab in combination with chemotherapy was well tolerated by patients with advanced solid tumors.

For instance, cancer patients will generally tolerate an immense amount of pain or discomfort during a chemotherapeutic study with the hope of prolonging survival or finding a cure, whereas patients experiencing a benign condition, such as a headache, will not. As an example, tricyclic antidepressants (TCAs) are very poorly tolerated and often produce severe side effects including sedation, orthostatic hypotension, and anticholinergic effects, whereas newer antidepressants have far fewer adverse effects and are well tolerated. Drug tolerability should not be confused with drug tolerance, which refers to subjects' reduced reaction to a drug following its repeated use.

The safety, tolerability, and pharmacokinetic profile of zaurategrast have been evaluated in 75 female and male healthy volunteers in three separate Phase 1 studies. Zaurategrast was well tolerated at oral doses up to 1000 mg given twice daily for 7 consecutive days with an adverse event profile comparable to that observed with placebo. There was no gender effect. The oral administration resulted in inhibition of VCAM-1 binding which could be maintained throughout a 12‑ or 24‑hour dose interval at well tolerated dosesBaker M, Shock A, Parton T et al. Pharmacokinetic and pharmacodynamic properties of the VLA-4 inhibitor CDP323.

The effects of estradiol can influence health in both positive and negative ways. In addition to the aforementioned effects, estradiol has antigonadotropic effects due to its estrogenic activity, and can inhibit ovulation and suppress gonadal sex hormone production. At sufficiently high dosages, estradiol is a powerful antigonadotropic, capable of suppressing testosterone levels into the castrate/female range in men. There are differences between estradiol and other estrogens, such as non-bioidentical estrogens like natural conjugated estrogens and synthetic estrogens like ethinylestradiol and diethylstilbestrol, with implications for pharmacodynamics and pharmacokinetics as well as efficacy, tolerability, and safety.

The tolerability and therapeutic window of amanitin-based ADCs has been determined in a variety of rodent and non- human primate models. Furthermore, amanitin has a water-soluble structure, resulting in antibody-drug conjugates with low tendency for aggregation, even using higher drug to antibody ratios or DAR. In preclinical mouse models of prostate cancer, α-(alpha)-amanitin conjugated to an antibody directed against prostate-specific membrane antigen (PSMA; FOLH1; GCPII) showed high antitumoral activity and caused complete remission at single i.v. doses of 150 μg/kg of toxin, with no more than marginal weight loss in treated animals.

It was first synthesized in late 1970s in the Laboratory of Organic Synthesis of Soviet Cancer Research Institute (which belonged to Academy of Medical Sciences of the USSR). Its first clinical trials in USSR were conducted in the late 1980s. Those trials confirmed its potential clinical efficacy in melanoma and better relative safety & improved tolerability over other nitrosourea antineoplastic compounds available at that time. In 1996 the compound obtained a Russian Pharmacologic Committee (a Russian analog of the U.S. Food and Drug Administration (FDA) and EMA in the European Community) regulatory approval for its use in melanoma under the trade name Aranoza.

It is TGA-labeled in Australia for migraine prevention, also in cases of neuropathic pain disorders, fibromyalgia and nocturnal enuresis. Amitriptyline is a popular off-label treatment for irritable bowel syndrome (IBS), although it is most frequently reserved for severe cases of abdominal pain in patients with IBS because it needs to be taken regularly to work and has a generally poor tolerability profile, although a firm evidence base supports its efficacy in this indication. Amitriptyline can also be used as an anticholinergic drug in the treatment of early-stage Parkinson's disease if depression also needs to be treated.Parkinson's disease .

HannaH demonstrated comparability between trastuzumab/hyaluronidase and intravenous trastuzumab based on co- primary endpoints of pathologic complete response and pharmacokinetics. Pathological complete response (pCR) was observed in 118 participants (45.4%) on the trastuzumab/hyaluronidase arm and in 107 participants (40.7%) receiving intravenous trastuzumab (95% CI for difference in pCR: -4.0; 13.4). SafeHER was a prospective, two-cohort, non-randomized, multinational, open-label trial assessing the overall safety and tolerability of trastuzumab/hyaluronidase with chemotherapy in 1,864 participants with HER2-positive breast cancer. Participants received a fixed dose of 600 mg trastuzumab/hyaluronidase every 3 weeks for 18 cycles.

Rapid technological change, increasing scale of industrial complexes, increased system integration, market competition, and other factors have been shown to increase societal risk in the past few decades. As such, risk assessments become increasingly critical in mitigating accidents, improving safety, and improving outcomes. Risk assessment consists of an objective evaluation of risk in which assumptions and uncertainties are clearly considered and presented. This involves identification of risk (what can happen and why), the potential consequences, the probability of occurrence, the tolerability or acceptability of the risk, and ways to mitigate or reduce probability of the risk.

A number of clinical studies have been conducted to investigate possible adverse events of this fixed combination corticosteroid and vitamin D analog. Safety and tolerability of calcipotriol/betamethasone dipropionate (Cal/BD) ointment has been assessed in a combined total of 2448 patients, exposed to treatment for 4 or 8 weeks (median weekly dose of 24.5 g). The most common adverse events for patients receiving Cal/BD were pruritus (3.1%), headache (2.8%), and nasopharyngitis (2.3%). Lesional/perilesional adverse events, defined as an adverse event located ≤2 cm from the lesional border, were reported by 8.7% of patients treated with Cal/BD ointment.

MPA has been studied at "massive" dosages of up to 5,000 mg per day orally and 2,000 mg per day via intramuscular injection, without major tolerability or safety issues described. Overdose is not described in the Food and Drug Administration (FDA) product labels for injected MPA (Depo-Provera or Depo-SubQ Provera 104). In the FDA product label for oral MPA (Provera), it is stated that overdose of an estrogen and progestin may cause nausea and vomiting, breast tenderness, dizziness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding. According to the label, treatment of overdose should consist of discontinuation of MPA therapy and symptomatic care.

Cost-minimization is a tool used in pharmacoeconomics to compare the cost per course of treatment when alternative therapies have demonstrably equivalent clinical effectiveness. Therapeutic equivalence (including adverse reactions, complications and duration of therapy) must be referenced by the author conducting the study and should have been done prior to the cost-minimization work. Since equal efficacy and equal tolerability is already demonstrated, there is no requirement to find a common efficacy denominator as would be the case when conducting a cost-effectiveness study. The author is not precluded from doing so through the use of "cost/cure" or "cost/year of life gained".

Because of their effectiveness, tolerability, and rapid onset of anxiolytic action, benzodiazepines are frequently used for the treatment of anxiety associated with panic disorder. However, there is disagreement among expert bodies regarding the long-term use of benzodiazepines for panic disorder. The views range from those holding benzodiazepines are not effective long-term and should be reserved for treatment-resistant cases to those holding they are as effective in the long term as selective serotonin reuptake inhibitors. The American Psychiatric Association (APA) guidelines note that, in general, benzodiazepines are well tolerated, and their use for the initial treatment for panic disorder is strongly supported by numerous controlled trials.

Due to its inferior effectiveness, tolerability, and safety, CPA is rarely used in the treatment of prostate cancer today, having largely been superseded by GnRH modulators and nonsteroidal antiandrogens. CPA is the only steroidal antiandrogen that continues to be used in the treatment of prostate cancer. Dose-ranging studies of CPA for prostate cancer were not performed, and the optimal dosage of CPA for the treatment of the condition has not been established. A dosage range of oral CPA of 100 to 300 mg/day is used in the treatment of prostate cancer, but generally 150 to 200 mg/day oral CPA is used.

17α-Estradiol has been studied as a therapeutic with potential to treat Alzheimer's and Parkinson's disease and other patients suffering from neurodegenerative diseases. 17α-Estradiol (as the sodium salt of its sulfated form) is a minor component (<10%) of hormone replacement products (such as conjugated estrogens, brand name Premarin), which have been studied and/or marketed in women and men since the 1930s. A survey of the effects of various forms of 17α-estradiol in humans on biochemical parameters, efficacy, estrogenicity, metabolism, safety, and tolerability has been published. Alfatradiol binds to the ERα and ERβ with 58% and 11% of the relative binding affinity of 17β-estradiol.

His early research included work on drug discovery and studies on the use of cephaloridine. Pertaining to trials of what became known as Augmentin, a combination of amoxicillin and clavulanic acid, he later recalled that “getting the right dose of amoxicillin proved important for efficacy and getting the right dose of clavulanic acid was key to tolerability”. In 1977, he published on the efficacies of cephamycins, including their parenteral administration, dosages and penetrations through normal and inflamed blood-brain barrier. He made comparisons of clindamycin with lincomycin against H. influenzae in vitro, and later demonstrated that clindamycin was active against Coxiella burnetti, the cause of Q fever.

To date there have been seven Phase I and Phase II clinical trials; four Phase I trials and three Phase II trials. The first Phase I clinical trial "A Study of the Safety, Tolerability, and Pharmacokinetics of MORAb-009, a Chimeric Monoclonal Antibody, in Subjects with Advanced Mesothelin- expressing Tumors" started in May 2006 with 24 enrolled participants and concluded in September 2008. No results have been posted. One of the Early Phase I trials "A Single-Dose Pilot Study of Radiolabeled Amatuximab (MORAb-009) in Mesothelin Over Expressing Cancers" started in July 2013 with seven enrolled participants and was terminated early in November 2013.

In 2016, MedImmune and AstraZeneca were developing tralokinumab for asthma (Ph3) and atopic dermatitis (Ph2b) while clinical development for moderate-to-severe ulcerative colitis and idiopathic pulmonary fibrosis (IPF) have been discontinued. In July of that year AstraZeneca licensed Tralokinumab to LEO Pharma for skin diseases. A phase 2b study of Tralokinumab found that treatment was associated with early and sustained improvements in atopic dermatitis symptoms and tralokinumab had an acceptable safety and tolerability profile, thereby providing evidence for targeting IL-13 in patients with atopic dermatitis. On 15 June 2017, Leo Pharma announced that they were starting phase 3 clinical trials with tralokinumab in atopic dermatitis.

Treatment decisions often follow formal or informal algorithmic guidelines. Treatment options can often be ranked or prioritized into lines of therapy: first-line therapy, second-line therapy, third-line therapy, and so on. First-line therapy (sometimes called induction therapy, primary therapy, or front-line therapy)National Cancer Institute > Dictionary of Cancer Terms > first-line therapy Retrieved July 2010 is the first therapy that will be tried. Its priority over other options is usually either: (1) formally recommended on the basis of clinical trial evidence for its best-available combination of efficacy, safety, and tolerability or (2) chosen based on the clinical experience of the physician.

Romark initially decided to focus on the possibility of treating chronic hepatitis C with nitazoxanide. The drug garnered interest from the hepatology community after three phase II clinical trials involving the treatment of hepatitis C with nitazoxanide produced positive results for treatment efficacy and similar tolerability to placebo without any signs of toxicity. A meta-analysis from 2014 concluded that the previous held trials were of low-quality and with held with a risk of bias. The authors concluded that more randomized trials with low risk of bias are needed to determine if Nitazoxanide can be used as an effective treatment for chronic hepatitis C patients.

Lamivudine/zidovudine (brand name Combivir) was introduced to the market with FDA approval in 1997. Its impact in history is significant as it was the first combination therapy with a fixed dose for HIV-positive people, and soon solidified its title as a gold standard as it was the most prescribed NRTI in initial HIV treatment for newly diagnosed patients. The arrival of Combivir was seen as a new revolution in HIV therapy, with its improved toxicity profile and tolerability, especially compared to the undesirable side effects of lone AZT therapy or the unfavorable facial and lipoatrophy seen in Stavudine monotherapy at that time.

A bottle of generic ibuprofen Ibuprofen was made available under prescription in the United Kingdom in 1969, and in the United States in 1974. In the years since, the good tolerability profile, along with extensive experience in the population, as well as in so-called phase-IV trials (postapproval studies), have resulted in the availability of ibuprofen OTC in pharmacies worldwide, as well as in supermarkets and other general retailers. Ibuprofen is its International nonproprietary name (INN), British Approved Name (BAN), Australian Approved Name (AAN) and United States Adopted Name (USAN). In the U.S., Motrin has been on the market since 1974, and Advil has been on the market since 1984.

In terms of geometric mean steady-state concentrations of (R)-bicalutamide, the departures from linearity were 4%, 13%, 17%, and 32% with dosages of 100, 150, 200, and 300 mg/day, respectively. There is a plateau in steady-state levels of (R)-bicalutamide with bicalutamide dosages above 300 mg/day, and, accordingly, dosages of bicalutamide of 300 to 600 mg/day result in similar circulating concentrations of (R)-bicalutamide and similar degrees clinically of efficacy, tolerability, and toxicity. Relative to 150 mg/day bicalutamide, levels of (R)-bicalutamide are about 15% higher at a dosage of 200 mg/day and about 50% higher at a dosage of 300 mg/day.

As evidenced by its effectiveness in the treatment of prostate cancer and other androgen-dependent conditions, the antiandrogenic actions of bicalutamide considerably exceed any impact of the increased levels of testosterone it results in. However, the elevated levels of estradiol remain unopposed by bicalutamide and are responsible for the gynecomastia and feminizing side effects it causes in men. Although bicalutamide monotherapy increases gonadotropin and sex hormone levels in men, this will not occur if bicalutamide is combined with an antigonadotropin such as a analogue, estrogen, or progestogen, as these medications maintain negative feedback on the HPG axis. monotherapy, including with bicalutamide, shows a number of tolerability differences from methods of androgen deprivation therapy that incorporate surgical or medical castration.

Generic medicines have the same active ingredient as the branded medicine, but are not always identical, which could affect some patients. The amount of drug that finally reaches the site of action is known as the bioavailability, directly impacting on the effectiveness and tolerability of a drug. For a generic medicine to be considered bioequivalent, the European Medicines Agency (EMEA) requires that the bioavailability lies between 80% and 125% of the original branded medicine. Patients can be switched between different generic medicines, which can mean that they might receive a generic medicine with effectively 25% more active ingredient than the branded medicine on one occasion and one with effectively 20% less active ingredient on the next.

Niaprazine (INN) (brand name Nopron) is a sedative-hypnotic drug of the phenylpiperazine group. It has been used in the treatment of sleep disturbances since the early 1970s in several European countries including France, Italy, and Luxembourg. It is commonly used with children and adolescents on account of its favorable safety and tolerability profile and lack of abuse potential. Originally believed to act as an antihistamine and anticholinergic, niaprazine was later discovered to have low or no binding affinity for the H1 and mACh receptors (Ki = > 1 μM), and was instead found to act as a potent and selective 5-HT2A and α1-adrenergic receptor antagonist (Ki = 75 nM and 86 nM, respectively).

Phase I clinical trial (NCT01546818)Safety and Immune Response Assessment Study of Killed-whole HIV-1 Vaccine (SAV001-H) in Chronic HIV-1 Infected Patients. Funded by Sumagen Canada, the government of Canada and the Bill and Melinda Gates Foundation,New HIV Vaccine Proves Successful In Phase 1 Human Trial it started in March 2012 to assess its safety, tolerability, and immune responses. This trial was a randomized, double blinded (both subject and investigator), placebo-controlled study, following intramuscular administration to 33 chronic HIV-1 infected individuals under the treatment with HAART. The study was completed in August 2013 and reported no serious adverse effects while boosting antibodies in the volunteers injected with SAV001-H vaccines.

Side effects of EES in men include breast tenderness, gynecomastia, feminization, sexual dysfunction, shortness of breath (6.8%), increased prolactin levels, and cardiovascular toxicity. The cardiovascular complications of EES in men with prostate cancer specifically include edema (4.5 to 26%), blood clots like deep vein thrombosis (4.1 to 15%) and pulmonary embolism, heart attack (2.3 to 18%), stroke (2.3 to 3.0%), and coronary artery disease (3.3%). EES has been described as having good tolerability compared to EE in the treatment of prostate cancer, a property that has been described as "remarkable". The unique C3 sulfonate ester of EES seems to reduce its hepatic estrogenicity, which in turn reduces its adverse effects on liver protein synthesis.

Although the perception and transmission of pain stimuli in the central nervous system have not been fully elucidated, extensive data support a role for serotonin and norepinephrine in the modulation of pain. Findings from clinical trials in humans have shown these antidepressants can to reduce pain and functional impairment in central and neuropathic pain conditions. This property of SNRIs might be used to reduce doses of other pain relieving medication and lower the frequency of safety, limited efficacy and tolerability issues. Clinical research data have shown in patients with GAD that the SNRI duloxetine is significantly more effective than placebo in reducing pain-related symptoms of GAD, after short-term and long-term treatment.

The opposite concept to drug tolerance is drug reverse tolerance (or drug sensitization), in which case the subject's reaction or effect will increase following its repeated use. The two notions are not incompatible and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers initially develop tolerance to alcohol (requiring them to drink larger amounts to achieve a similar effect) but excessive drinking can cause liver damage, which then puts them at risk of intoxication when drinking even very small amounts of alcohol. Drug tolerance should not be confused with drug tolerability, which refers to the degree to which overt adverse effects of a drug can be tolerated by a patient.

The typical antipsychotic haloperidol has been the most used drug in treatment trials for stuttering. In double-blind placebo-controlled trials with objective speech measures, the group receiving haloperidol displayed significant improvement after a 8-week trial. However, the mechanism of action of this first generation psychotic bore important side effects that affected the tolerability in patients and maintaining the improved speech required that subjects keep taking the drug. Moreover, the trial was conducted before the full extent of the risks of using neuroleptics was appreciated; the extrapyramidal symptoms and the possible permanent tardive dyskinea that could result now qualify the drug as dangerous and possibly disproportionate in the treatment of stuttering.

The slightly higher preference for SSRIs over SNRIs as a first choice for treatment of anxiety disorders may have been influenced by the observation of poorer tolerability of the SNRIs in comparison to SSRIs in systematic reviews of studies of depressed patients. Duloxetine is also indicated for the treatment of chronic musculoskeletal pain and neuropathic pain associated with diabetes mellitus, and may be a good option for people with both conditions. Side effects common to both SNRIs include anxiety, restlessness, nausea, weight loss, insomnia, dizziness, drowsiness, sweating, dry mouth, sexual dysfunction and weakness. In comparison to SSRIs, the SNRIs have a higher prevalence of the side effects of insomnia, dry mouth, nausea and high blood pressure.

In July 2004, Actelion started a clinical trial of miglustat to treat Tay–Sachs disease, particularly late- onset Tay–Sachs with an estimated enrollment of 10 subjects; the trial ended August 2007.Clinicaltrials.gov Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses Accessed 1 September 2014 In November 2007, Actelion initiated a clinical trial with miglustat in people with cystic fibrosis (CF) who have the ΔF508 in both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene; the study ended in March 2008.Clinicaltrials.gov Miglustat / OGT 918 in the Treatment of Cystic Fibrosis Accessed 1 September 2014 The cystic fibrosis trial showed no effect.

Subsequent research found that moclobemide is well tolerated in elderly patients and far superior to tricyclic antidepressants in terms of side effects, tolerability and overdose. With regard to effectiveness in the treatment of depression, moclobemide was determined to be as effective as all major antidepressant drug classes. There is no need for dietary restrictions in contrast to people on irreversible MAOIs and apart from an important interaction with other serotonergic enhancing agents such as SSRIs and pethidine, there are few serious drug interactions and because of these benefits, moclobemide became regarded as a beneficial addition to medical 'prescribing arsenal'. Additionally moclobemide was found, unlike most other antidepressants on the market, to actually improve all aspects of sexual function.

In October 2018, Compugen announced a clinical collaboration and equity investment agreement with Bristol-Myers Squibb. Under the terms of the agreement, Bristol Bristol- Myers Squibb will supply Opdivo®, its PD-1 inhibitor, for the combination arm of Compugen’s Phase 1 study designed to evaluate the safety and tolerability of COM701 and Opdivo in four tumor types, including non-small cell lung, ovarian, breast, and endometrial cancer. In addition, Bristol-Myers may initiate and fund clinical trials that assess combinations of multiple checkpoint inhibitors, including PVRIG (the target of COM701), and TIGIT. In conjunction with the collaboration agreement, Bristo-Mayers Squibb made a $12 million equity investment in Compugen, holding approximately 4% of the company.

Decisions on the monetary policy rate (MPR), the reference interest rate for the economy, usually take place on a monthly basis in the monetary policy meetings, although extraordinary meetings can be called. If inflation expectations are diverging from the 3% target or if there are events since the previous meeting with an anticipated effect in the price level, the CBoC might change the MPR. The monetary policy is carried out through the daily interbank interest rate. Inflation has followed a relatively stable trajectory since the inception of the targeting regime, remaining under 10% ever since; yearly inflation only surpassed the tolerability threshold of 4% in 2007 and 2008, with respective readings of 4.4% and 8.7% in historical terms.

Despite its greatly improved tolerability and safety profile however, bicalutamide does still have a small risk of elevated liver enzymes and association with very rare cases of liver damage and lung disease. Nonsteroidal antiandrogens like bicalutamide may be a particularly favorable option for transgender women who wish to preserve sex drive, sexual function, and/or fertility, relative to antiandrogens that suppress testosterone levels and can greatly disrupt these functions such as cyproterone acetate and GnRH modulators. However, estrogens suppress testosterone levels and at high doses can markedly disrupt sex drive and function and fertility on their own. Moreover, disruption of gonadal function and fertility by estrogens may be permanent after extended exposure.

This multiphase trial aimed to further evaluate the safety of tolerability of Abituzumab in combination therapy with cetuximab and irinotecan in the Phase I portion of the trial. Cetixumab, a monoclonal antibody, that targets epidermal growth factor receptor (EGFR), and irinotecan, a topoisomerase I inhibitor, can be used in combination as standard of care for treating colorectal cancer. The Phase II portion of the trial sought to compare the efficacy of Abituzumab, cetuximab, and irinotecan compared to cetuximab and irinotecan in patients with KRAS (exon 2) wild-type metastatic colorectal cancer. Patients included in the study failed treatment with oxaliplatin, and initial safety studies included comparing Abituzumab, cetuximab, and irinotecan with standard of care.

It remains unclear what daily intake of gluten is adequate and how long the gluten challenge should last. Some protocols recommend eating a maximum of 10 g of gluten per day for 6 weeks. Nevertheless, recent studies have shown that 2-week challenge of 3 g of gluten per day may induce histological and serological abnormalities in most adults with proven coeliac disease. This newly proposed protocol has shown higher tolerability and compliance, and it has been calculated that its application in secondary-care gastrointestinal practice would identify celiac disease in 7% patients referred for suspected non-coeliac gluten sensitivity, while in the remaining 93% would confirm non-coeliac gluten sensitivity, but is not yet universally adopted.

Consequentially, it was thought that EMP would preferentially deliver the alkylating normustine moiety to these tissues, allowing for reduced cytostatic effects in healthy tissues and hence improved efficacy and tolerability. However, subsequent research found that there is very limited and slow cleavage of the normustine ester and that EMP is devoid of alkylating activity. In addition, it appears that estramustine and estromustine may be preferentially accumulated in estrogen target tissues not due to affinity for the estrogen receptors, but instead due to affinity for the distinct EMBP. Extremely high, pregnancy-like levels of estradiol may be responsible for the leukocytosis (increased white blood cell count) that is observed in individuals treated with EMP.

HJ (Iran) and HT (Cameroon) v Secretary of State for the Home Department [2010] UKSC 31 is a case decided by the Supreme Court of the United Kingdom concerning two men, from Iran and Cameroon respectively, claiming asylum in the United Kingdom on the grounds of their homosexuality. The men's claims had previously been turned down on the basis they would not face persecution in their own countries if they would conceal their sexuality. The appeal therefore centred on the question as to whether the men on their return could reasonably be expected to tolerate this requirement of discretion; the so- called 'discretion' or 'reasonable tolerability' test. Interventions were made by the Equality and Human Rights Commission and the United Nations High Commissioner for Refugees.

The studies on SAR were double-blind, placebo-controlled, parallel-group involving male and female patients over 12 year of age with symptomatic disease at the beginning of the study. Nasal symptoms (sneezing, rhinorrhea, nasal itching and congestion) were assessed both before treatment and during treatment period on a daily basis. Non nasal symptoms (itchy eye, watery eye, itchy ear and palate) were also assessed according to a 0–3 scale, so that the Total Symptoms Score (TSS) and other related parameters could clearly reflect daily evolution of SAR in each patient and treatment group. Parameters such as quality of life and discomfort were also assessed, and in the same way the type and frequency of AE, tolerability and general safety of treatment were registered.

In 2018, Polosa Riccardo founded the Center of Excellence for the acceleration of HArm Reduction (CoEHAR), University of Catania, Italy. He was the Principal Investigator of ECLAT- first randomized controlled trial in the world about effectiveness and tolerability of e-cigarettes. The study showed that in smokers not intending to quit, the use of e-cigarettes, with or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects. He has been involved in the behavioural, clinical, physiological and toxicological evaluation of e-cigarettes for over 6 years and designed and conducted dozens of research studies, working with smoking cessation specialists, clinical psychologists, experienced vapers, epidemiologists, biostatisticians, chemists, toxicologists, and biologists from all over the world.

In the United States, the use of surgery declined from 41% of cases in 1998 to 30% by 2009, the year that the Food and Drug Administration approved the use of the newer techniques. These improvements in surgical techniques have allowed many tumours to be resected (removed) by transoral (through the mouth) surgical approaches (TOS), using transoral endoscopic head and neck surgery (HNS). Consequently, surgery became used more, increasing to 35% of cases by 2012. This approach has proven safety, efficacy and tolerability, and includes two main minimally invasive techniques, transoral robotic surgery (TORS) and transoral laser microsurgery (TLM). No direct comparisons of these two techniques have been conducted, and clinical trials in head and neck cancer such as ECOG 3311 allow either.

Nevertheless, recent studies have shown that a 2-week challenge of 3 g of gluten per day may induce histological and serological abnormalities in most adults with proven celiac disease. This new proposed protocol has shown higher tolerability and compliance. It has been calculated that its application in secondary-care gastrointestinal practice would identify celiac disease in 7% of patients referred for suspected NCGS, while the remaining 93% would be confirmed as NCGS; this is not yet universally adopted. For people on a gluten-free diet who are unable to perform an oral gluten challenge, an alternative to identify possible celiac disease is an in vitro gliadin challenge of small bowel biopsies; this test is only available at selected specialized tertiary-care centers.

In children and adolescents, fluoxetine is the antidepressant of choice due to tentative evidence favoring its efficacy and tolerability. In pregnancy, fluoxetine is considered a category C drug by the USA Food and Drug Administration (FDA). Evidence supporting an increased risk of major fetal malformations resulting from fluoxetine exposure is limited, although the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK has warned prescribers and patients of the potential for fluoxetine exposure in the first trimester (during organogenesis, formation of the fetal organs) to cause a slight increase in the risk of congenital cardiac malformations in the newborn. Furthermore, an association between fluoxetine use during the first trimester and an increased risk of minor fetal malformations was observed in one study.

In a clinical trial that compared it to haloperidol in the treatment of schizophrenia it was found to produce significantly superior overall symptom control. In another clinical trial perospirone was compared with mosapramine and produced a similar reduction in total PANSS score, except with respect to the blunted affect part of the PANSS negative score, in which perospirone produced a significantly greater improvement. In an open-label clinical trial comparing aripiprazole with perospirone there was no significant difference between the two treatments discovered in terms of both efficacy and tolerability. In 2009 a clinical trial found that perospirone produced a similar reduction of PANSS score than risperidone and the extrapyramidal side effects was similar in both frequency and severity between groups.

A clinical trial comparing its efficacy and tolerability with amitriptyline in the treatment of irritable bowel syndrome showed that tianeptine was at least as effective as amitriptyline and produced less prominent adverse effects such as dry mouth and constipation. Tianeptine has been reported to be very effective for asthma. In August 1998, Dr. Fuad Lechin and colleagues at the Central University of Venezuela Institute of Experimental Medicine in Caracas published the results of a 52-week randomized controlled trial of asthmatic children; the children in the groups that received tianeptine had a sharp decrease in clinical rating and increased lung function. Two years earlier, they had found a close, positive association between free serotonin in plasma and severity of asthma in symptomatic persons.

The safety and efficacy of cenobamate to treat partial-onset seizures was established in two randomized, double-blind, placebo-controlled studies that enrolled 655 adults. In these studies, patients had partial-onset seizures with or without secondary generalization for an average of approximately 24 years and median seizure frequency of 8.5 seizures per 28 days during an 8-week baseline period. During the trials, doses of 100, 200, and 400 milligrams (mg) daily reduced the percent of seizures per 28 days compared with the placebo group. The recommended maintenance dose, following a titration (medication adjustment) period, is 200 mg daily; however, some patients may need an additional titration to 400 mg daily, the maximum recommended dose, based on their clinical response and tolerability.

Examples include the production of multi-specific Affimer molecules to target and recruit specific cells, fusion to Fc fragments or albumin binders to tune their half-life in vivo and for use as the targeting moiety in chimeric receptors or modified to carry a toxin in Affimer-drug conjugates. Affimer therapeutics are in discovery and preclinical development to tackle blood clotting disorders, antibiotic resistance, phenotypic drug discovery models and cancer, both via CAR-T cell therapy and as immune checkpoint inhibitors. Early studies using ex vivo human samples showed low immunogenicity associated with the Affimer scaffold, at levels comparable to a marketed antibody therapeutic. Furthermore, initial preclinical studies showed good efficacy and tolerability of the anti-PDL1 immuno-oncology Affimer therapeutic in mice.

Clevegen is a new cancer immunotherapy drug under development in Finland by Faron Pharmaceuticals. The drug is an anti-Clever-1 antibody which can convert immune suppressive type-2 tumour-associated macrophages (TAMs) to immune active type-1 microphages and has the potential for wide use in oncology. It is currently (2019) undergoing trials (codename MATINS) as an innovative treatment for metastatic or inoperable solid tumours such as cutaneous melanoma and hepatobiliary/hepatocellular, pancreatic, ovarian and colorectal cancers, all of which host a significant number of Clever-1-positive TAMs and represent some 2 million cases annually worldwide. Following encouraging results of early European trials regarding the drugs tolerability and safety the MATINS programme is being extended to the USA.

A 2004 meta-analysis comprising three randomized placebo-controlled studies with a total of 173 patients suggested that iberogast was more effective than placebo in relieving "the most bothersome gastrointestinal symptom" of functional dyspepsia as identified by each patient. Additionally, a single reference-controlled study was discussed, comparing iberogast to the prokinetic cisapride in the treatment of "'functional dyspepsia of the dysmotility type'" and finding no significant differences in efficacy or tolerability. This paper noted that, while iberogast seems to consistently provide symptomatic relief to patients, its efficacy is more evident "with associated symptoms of gastro-oesophageal reflux or predominance of epigastric pain." It suggests a synergy of therapeutic mechanisms provided by the complex interactions between the GI tract and each individual component of iberogast.

After being found to be active against SARS-CoV-2 in March 2020, MK-4482 was tested in a preliminary human study for "Safety, Tolerability, and Pharmacokinetics" in healthy volunteers in the UK and US. In June 2020, Ridgeback Biotherapeutics announced it was moving to Phase II trials to test the efficacy of the drug as a treatment for COVID-19.. Two trials of small numbers of hospitalized and non-hospitalized patients in the US and the UK were underway in July. In late July 2020, and without yet releasing any medical data, Merck, which had been partnering with Ridgeback Biotherapeutics on developing the drug, announced its intention to move MK-4482 to late stage trials beginning in September 2020.

The company announced in late 2005 that the U.S. Food and Drug Administration had approved the protocol for the Phase IIb clinical trial of Tcelna. The multicenter, randomized, double blind, placebo-controlled Phase IIb clinical study on 150 patients was designed to evaluate the efficacy, safety and tolerability of the therapy with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RR-MS) patients. The first phase of the trial finished in March 2008."Opexa Therapeutics Announces Completion Of Mid Study Descriptive Analysis On Phase IIb Trial Of Tcelna" All patients who completed the trial were to be eligible for an optional one-year extension study, OLTERMS, to receive Tcelna open-label without a placebo group; however, that program was terminated suddenly for lack of funding.

The NANORAY-1100 study is a multicenter, multi-arm, that aims to evaluate the safety, efficacy, and tolerability of NBTXR3 activated by radiotherapy in combination with anti-PD-1 therapy in Locoregional recurrent (LRR) or recurrent and metastatic (R/M) head and neck squamous-cell carcinoma (HNSCC) and lung and Liver metastasis. It aims to evaluate the hypothesis that the combination of NBTXR3 activated by RT with anti-PD-1 therapy will act synergistically to enhance the therapeutic window of radiation therapy by maximizing the local effect, overcoming radio- resistance, increasing the efficacy of immunotherapy, and potentially producing an abscopal effect for improved distant tumor control. As of 2020, the study is recruiting participants in several states in the United States.

An antispasmodic effect on the upper digestive tract in vitro and in animal studies is considered sufficiently documented. The efficacy of the herbal products in humans is considered plausible but yet unproven in clinical studies. Numerous clinical studies in its amphocholeretic uses in humans have demonstrated the tolerability and safety of dosages used, but there has only been one small double-blind trial with placebos which was inconclusive regarding efficacy. A larger double-blind trial with placebos investigating and comparing its use in the treatment of pain and distension due to irritable bowel syndrome with Curcuma demonstrated no statistically significant differences between treatment groups (although use of either herb appeared to slightly worsen either distension or pain respectively, compared to placebo use).

An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including flurazepam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy in elderly persons. Tolerability in elderly patients, however, is improved marginally in that benzodiazepines have moderately higher risks of falls, memory problems, and disinhibition ("paradoxical agitation") when compared to non-benzodiazepine sedatives. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people.

Nventa originally advanced HspE7 as a single-agent therapy into multiple Phase 2 clinical trials with positive results, including trials in cervical dysplasia and recurrent respiratory papillomatosis (RRP). These trials were initiated prior to the discovery that potency could be greatly enhanced by addition of a vaccine adjuvant,International HPV Conference Poster: “NVENTA PRESENTS HSPE7 DATA AT INTERNATIONAL HPV CONFERENCE” / Nventa Press Release, November 5, 2007 and, as a result, Nventa is currently developing HspE7 combined with the adjuvant Poly-ICLC. A Phase 1b study has been completed assessing the safety and tolerability of HspE7 with Poly-ICLC in four cohorts totaling 17 patients with CIN. All patients were administered 500 mcg of HspE7 with each of the four cohorts receiving escalating doses of adjuvant – 50, 500, 1,000 and 2,000 mcg.

However, the results of this study were considered inconclusive because neither the LY-2140023 or the olanzapine (active control) groups demonstrated significant differences in treatment as compared to the placebo. Due to the possibility of a heightened placebo response that may have reduced the ability to detect a significant response to the drug across the LY-2140023 and olanzapine groups, clinical studies of the drug's efficacy were continued. A phase II, multicenter, randomized, parallel, active-controlled study with an open-label design was conducted in 2013 to investigate tolerability, efficacy and adverse effects of long-term treatment with LY-2140023. Patients receiving LY-2140023 were compared to patients receiving other antipsychotic medications, including olanzapine, risperidone, and aripiprazole, for a 24-week treatment phase and optional 28-week extension phase.

The STEPS trial (an acronym for Study of Neurontin: Titrate to Efficacy, Profile of Safety) was a clinical trial sponsored by Parke-Davis (now Pfizer) to evaluate the anticonvulsant Neurontin. It is notable for being a seeding trial to promote that drug and for contributing to the drug companies loss in the court case Franklin v. Parke-Davis. Detailed documents were released due to litigation against Parke-Davis and reviewed by several researchers in a 2011 Annals of Internal Medicine article. The STEPS trial was presented as a phase IV clinical trial with the stated objective to "study efficacy, safety, tolerability, and quality of life among gabapentin users", however the trial was actually completely uncontrolled and unblinded and the scientific validity of the trial was considered dubious by independent external sources.

Romark Laboratories has announced encouraging results from international Phase I and II clinical trials evaluating a controlled release version of nitazoxanide in the treatment of chronic hepatitis C virus infection. The company used 675 mg and 1,350 mg twice daily doses of controlled release nitazoxanide showed favorable safety and tolerability throughout the course of the study, with mild to moderate adverse events. Primarily GI-related adverse events were reported. Nitazoxanide has gone through Phase II clinical trials for the treatment of hepatitis C, in combination with peginterferon alfa-2a and ribavirin. A randomised double- blind placebo-controlled study published in 2006, with a group of 38 young children (Lancet, vol 368, page 124-129) concluded that a 3-day course of nitazoxanide significantly reduced the duration of rotavirus disease in hospitalized pediatric patients.

An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and lasting benefits of non-drug treatments for insomnia in adults of all age groups and that these interventions are underused. Compared with the benzodiazepines, the nonbenzodiazepine sedative-hypnotics offer little if any advantages in efficacy or tolerability in elderly persons. It was found that newer agents such as the melatonin agonists may be more suitable and effective for the management of chronic insomnia in elderly people. Long-term use of sedative- hypnotics for insomnia lacks an evidence base and is discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls.

Side effects are generally similar to other antipsychotics. The drug has a relatively well tolerated side effect profile, with low propensity for QTc interval changes, weight gain and lipid-related adverse effects. In a 2013 meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs it was found to produce the second least (after haloperidol) weight gain, the least QT interval prolongation, the fourth most extrapyramidal side effects (after haloperidol, zotepine and chlorpromazine) and the sixth least sedation (after paliperidone, sertindole, amisulpride, iloperidone and aripiprazole). As with other atypical neuroleptics, lurasidone should be used with caution in the elderly because it puts them at an increased risk for a stroke or transient ischemic attack; however, these risks are not likely to be greater than those associated with antipsychotics of other classes.

Given its good physicochemical properties, promising pharmacokinetic and efficacy profile, the molecule was recently approved as a preclinical candidate and is now entering GLP toxicology studies with the aim of entering Phase I studies in humans in late 2010. If its safety and tolerability are acceptable, cipargamin would be the first antimalarial not belonging to either the artemisinin or peroxide class to go into a proof-of-concept study in malaria. If cipargamin behaves similarly in people to the way it works in mice, it may be possible to develop it into a drug that could be taken just once - far easier than current standard treatments in which malaria drugs are taken between one and four times a day for up to seven days. Cipargamin also has properties which could enable it to be manufactured in pill form and in large quantities.

Diethylstilbestrol dipalmitate (brand names Palmestril, Stilpalmitate), also known as stilpalmitate, is a synthetic, nonsteroidal estrogen of the stilbestrol group and an ester of diethylstilbestrol (DES) that was formerly marketed but is now no longer available. Its actions and uses are essentially the same as those of DES, but it is absorbed more slowly and for this reason has a much longer duration of action and improved tolerability in comparison. A single 5 mg intramuscular injection of DES dipalmitate in oil solution has been found to have an average duration of action of 8 to 10 weeks in terms of relief of menopausal symptoms, with a duration of as long as 15 to 16 weeks occurring in some women. A single 15 or 20 mg intramuscular injection of DES dipalmitate in oil solution will control menopausal symptoms for 3 months or longer.

In partnership with the Grupo Español de Investigación en Neurooncología GEINO, in Spain, Tilray supplied medical cannabis products for the trial testing the efficacy and tolerability of medical cannabis as treatment for glioblastoma. In August 2019, Tilray announced a partnership with New York University and shipped CBD to the school so that researchers could study its potential ability to treat alcohol use disorder and post-traumatic stress disorder. In the same month, Tilray signed an agreement with Cannamedical Pharma GmbH to export $3.3 million worth of medical cannabis from its Portugal facility to German patients, marking Tilray's first export from Tilray Portugal Unipessoal, Lda. In partnership with New York University, Tilray imported medical cannabis to the U.S. in October 2019 to support a clinical trial studying its efficacy in treating disorders caused by breast cancer treatments.

In November 2013, Discovery Laboratories began its phase II clinical program of aerosolized KL4 since U.S. Food and Drug Administration (FDA) had cleared the investigational new drug (IND) application. The phase II consists of two steps to evaluate the safety and tolerability of the drug and determine the optimal dose for premature infants with respiratory distress syndrome (RDS) In October 2013, Discovery Laboratories received the agreement of updating Surfaxin (lucinactant) Intratracheal Suspension from the U.S. Food and Drug Administration (FDA) to prevent respiratory distress syndrome (RDS) in premature infants. In September 2012, Discovery Laboratories started the four research projects to explore the KL4 surfactant technology for acute lung injury (ALI). These projects are funded through government-sponsored, biodefense-related initiatives under the Project Bioshield Act of 2004 and the Pandemic and All Hazards Preparedness Act of 2006.

As such, besides strong serotonin reuptake inhibition, clomipramine at high doses might also block dopamine receptors to treat OCD symptoms, and this could additionally or alternatively be involved in its possible effectiveness advantage over SSRIs. Although clomipramine is probably more effective in the treatment of OCD compared to SSRIs, it is greatly inferior to them in terms of tolerability and safety due to its lack of selectivity for the SERT and promiscuous pharmacological activity. In addition, clomipramine has high toxicity in overdose and can potentially result in death, whereas death rarely, if ever, occurs with overdose of SSRIs. It is for these reasons that clomipramine, in spite of potentially superior effectiveness to SSRIs, is now rarely used as a first- line agent in the treatment of OCD, with SSRIs being used as first-line therapies instead and clomipramine generally being reserved for more severe cases and as a second-line agent.

SMSs were developed because there are many different subtypes of serotonin receptors (at least 15 in total are currently known) and not all of these receptors appear to be involved in the antidepressant effects of SRIs. Some serotonin receptors seem to play a relatively neutral or insignificant role in the regulation of mood, but others, such as 5-HT1A autoreceptors and 5-HT7 receptors, appear to play an oppositional role in the efficacy of SRIs in treating depression. As such, a drug which combines the actions of, say, an SRI, 5-HT1A partial agonism, and 5-HT7 receptor antagonism, could, in theory, have the potential to prove more effective than pure SRIs. Alternatively, antagonism of 5-HT3 – a receptor that is involved in the regulation of nausea, vomiting, and the gastrointestinal tract – could counteract the undesirable increase in activation of this receptor mediated by SRIs, thereby potentially improving tolerability.

An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including quazepam, the nonbenzodiazepine sedative/hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative/hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls.

An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including estazolam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative- hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls.

With this in mind, Pasinetti initiated a drug repurposing study for AD, screening FDA- approved drugs and natural compounds for amyloid-lowering and anti-Aβ aggregation activities, and identified candidates for in vivo testing in AD animal models. As a result of this study, Pasinetti's laboratory identified antihypertensive drugs lacking cardiovascular side effects but with enhanced anti-Aβ oligomerization activity. Pasinetti's research has also validated that repurposing drugs that have already been well-characterized in terms of tolerability and safety profile may have several advantages over novel drugs. These studies provide new information about the potentially detrimental role of commonly prescribed drugs that can be used as a reference for physicians to consider, particularly when treating chronic degenerative disorders such as AD. Following these findings, as Chief of the Friedman Brain Institute Center of Excellence for Novel Approaches to Neurodiagnostics and Neurotherapeutics, Pasinetti developed drug discovery programs for Alzheimer's disease.

Documents released during a court case indicate that the Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness (ADVANTAGE) trial of Vioxx conducted by Merck may have been a seeding trial, with the intention being to introduce the drug to physicians rather than test its efficacy.New Scientist: New York Times: It appears Merck knew about the potential criticism they would face; an internal email suggested: "It may be a seeding study, but let's not call it that in our internal documents". The 2003 study was originally published in the Annals of Internal Medicine but was strongly criticized for its deception by the journal's editors in a 2008 editorial, calling for greater responsibility in academia to end the practice of "marketing in the guise of science". In the STEPS trial Pfizer presented their drug Neurontin in a way that merged pharmaceutical marketing with research.

Data from these trials showed encouraging results for safety, tolerability, immunogenicity and pharmacokinetic profile, and signals of clinical activity in regards to muscle strength (Manual Muscle Testing) and disease burden (Individualized Neuromuscular Quality of Life score – INQoL).PR Newswire: aTyr Pharma Presents Additional Data for Resolaris™ Phase 1b/2 Trial in Adult Patients with Facioscapulohumeral Muscular Dystrophy at the 21st International Annual Congress of the World Muscle Society (Oct. 6, 2016)NASDAQ Globe Newswire: aTyr Pharma Presents Analyses of Resolaris Phase 1b/2 Trial in Patients with Limb Girdle Muscular Dystrophy 2B and Facioscapulohumeral Muscular Dystrophy at the American Academy of Neurology 69th Annual Meeting (April 24, 2016)NASDAQ Globe Newswire: aTyr Pharma Announces Promising Top-Line Results from Resolaris™ Phase 1b/2 Clinical Trial in Patients with Early Onset Facioscapulohumeral Muscular Dystrophy (April 24, 2017) ATyr's primary focus is on ATYR1923, a clinical stage product candidate which binds to the NRP2 receptor and is designed to down regulate immune engagement in interstitial lung diseases (ILDs). ATYR1923 is currently being investigated in a clinical trial in patients with pulmonary sarcoidosis.

Lestaurtinib was filed as Investigational New Drug (IND) number 76431. Initial Phase I studies with lestaurtinib involved determination of pharmacokinetic parameters following a single dose in healthy volunteers. Next, safety and tolerability were investigated in a Phase I trial involving 30 volunteers with advanced solid tumors or lymphoma. Although there were no notable tumor responses, a strong correlation was noted between dose and adverse events, with the primary adverse event reported being gastrointestinal reaction. A Phase II study in 18 patients with pancreatic cancer was initiated for combination treatment with lestaurtinib and gemcitabine, but efficacy of lestaurtinib was not observed. In 2004, a Phase I/II study involved 17 patients at 2 locations with relapsed, refractory poor-risk AML with FLT3 mutations; this study demonstrated effective FLT3 inhibition by lestaurtinib. A multi-center Phase II study of 29 patients above the age of 60 was initiated for treatment with lestaurtinib alone; the results, reported in 2006, indicated that the primary endpoint of complete remission was not achieved in any participants. Despite this failure, another multi-center Phase II trial involving 42 patients combined lestaurtinib with conventional chemotherapy; the results, reported in 2005, indicated that twice as many patients showed a clinical response when treated with lestaurtinib as compared to those not treated.