Efficacy and Safety of Iloperidone in Bipolar Mania: A Double-Blind, Placebo-Controlled Study.

To determine if iloperidone, a second-generation antipsychotic, reduces symptoms of bipolar mania. This phase 3, randomized, double-blind, placebo-controlled study was conducted in adults with bipolar mania at 27 US and international sites between April 2021 and September 2022. Participants were randomized 1:1 to iloperidone (up to 24 mg/d given twice daily) or placebo for 4 weeks.

Simulated driving performance in healthy adults after night-time administration of 20 mg tasimelteon.

An impairment in next day driving performance has been reported for almost every drug currently United States Food and Drug Administration (FDA) approved for improvement of sleep in chronic and transient insomnia. Tasimelteon, a melatonin receptor agonist, demonstrated significant improvements in night-time sleep, daytime naps, and sleep timing in non-24-hr sleep-wake disorder (Non-24) by entraining these patients to a 24-hr day as measured by melatonin and cortisol rhythms. Given this new mechanism of action of entraining the biological clock, we conducted a study to evaluate the potential effect tasimelteon may have on the ability to operate a motor vehicle.

Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials.

Background: Most totally blind people have non-24-hour sleep-wake disorder (non-24), a rare circadian rhythm disorder caused by an inability of light to reset their circadian pacemaker. In two consecutive placebo-controlled trials (SET and RESET), we assessed safety and efficacy (in terms of circadian entrainment and maintenance) of once-daily tasimelteon, a novel dual-melatonin receptor agonist.

Methods: We undertook the placebo-controlled, randomised, double-masked trials in 27 US and six German clinical research centres and sleep centres.

Clinical assessment of drug-drug interactions of tasimelteon, a novel dual melatonin receptor agonist.

Tasimelteon ([1R-trans]-N-[(2-[2,3-dihydro-4-benzofuranyl] cyclopropyl) methyl] propanamide), a novel dual melatonin receptor agonist that demonstrates specificity and high affinity for melatonin receptor types 1 and 2 (MT1 and MT2 receptors), is the first treatment approved by the US Food and Drug Administration for Non-24-Hour Sleep-Wake Disorder. Tasimelteon is rapidly absorbed, with a mean absolute bioavailability of approximately 38%, and is extensively metabolized primarily by oxidation at multiple sites, mainly by cytochrome P450 (CYP) 1A2 and CYP3A4/5, as initially demonstrated by in vitro studies and confirmed by the results of clinical drug-drug interactions presented here. The effects of strong inhibitors and moderate or strong inducers of CYP1A2 and CYP3A4/5 on the pharmacokinetics of tasimelteon were evaluated in humans.

Absolute Bioavailability of Tasimelteon.

Tasimelteon is a novel dual melatonin receptor agonist and is the first treatment approved by the US Food and Drug Administration for Non-24-Hour Sleep-Wake Disorder. This study was conducted to assess the absolute bioavailability of tasimelteon and to further assess the single-dose pharmacokinetics, safety, and tolerability of oral and intravenous (IV) routes of administration of the drug. This study was an open-label, single-dose, randomized, 2-period, 2-treatment, 2-sequence, crossover study in which 14 healthy volunteers were randomly administered tasimelteon as either a 20-mg capsule or IV administration of 2 mg infused over 30 minutes.

Pharmacokinetics of the dual melatonin receptor agonist tasimelteon in subjects with hepatic or renal impairment.

Tasimelteon is a circadian regulator that resets the master clock in the suprachiasmatic nuclei of the hypothalamus by binding to both melatonin MT1 and MT2 receptors making it a dual melatonin receptor agonist. Tasimelteon has been approved by the United States Food and Drug Administration for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24). Two prospective, single-center, open-label studies evaluated the pharmacokinetics of tasimelteon and its main metabolites after a single 20 mg dose administered to subjects with mild or moderate hepatic impairment or severe renal impairment, including subjects on dialysis compared to healthy controls.

Efficacy of iloperidone in the treatment of schizophrenia: initial phase 3 studies.

Iloperidone is an atypical antipsychotic in development for the treatment of schizophrenia. This report examines efficacy results from three 6-week, randomized, double-blind, placebo- and active comparator-controlled studies in patients with schizophrenia or schizoaffective disorder. Multiple doses of iloperidone were studied.