"SB-649868"

Neuroendocrine and sympathetic responses to an orexin receptor antagonist, SB-649868, and Alprazolam following insulin-induced hypoglycemia in humans. The orexin-hypocretin system is important for translating peripheral metabolic signals and central neuronal inputs to a diverse range of behaviors, from feeding, motivation and arousal, to sleep and wakefulness. Orexin signaling is thus an exciting potential therapeutic target for disorders of sleep, feeding, addiction, and stress. Here, we investigated the low dose pharmacology of orexin receptor antagonist, SB-649868, on neuroendocrine, sympathetic nervous system, and behavioral responses to insulin-induced hypoglycemic stress, in 24 healthy male subjects (aged 18-45 years; BMI 19.0-25.9 kg/m(2)), using a randomized, double-blind

The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia. To assess the acute effects of SB-649868 in male subjects with Primary Insomnia with regard to (1) objective and subjective sleep parameters, (2) safety and tolerability, (3) next-day residual effects. Multicenter, randomized, double-blind, placebo-controlled crossover study using a complete set of Williams orthogonal Latin Squares 9 sleep centers in Germany 52 male subjects with a diagnosis of primary insomnia (difficulty in sleep initiation and maintenance) confirmed by polysomnography SB-649868 (10, 30, 60 mg) and placebo administered after dinner 90 minutes before bedtime Sleep effects assessed by polysomnography during 2 consecutive nights and by sleep questionnaires completed by subjects

Differential effects of a dual orexin receptor antagonist (SB-649868) and zolpidem on sleep initiation and consolidation, SWS, REM sleep, and EEG power spectra in a model of situational insomnia. Orexins have a role in sleep regulation, and orexin receptor antagonists are under development for the treatment of insomnia. We conducted a randomised, double-blind, placebo-controlled, four-period crossover study to investigate the effect of single doses of the dual orexin receptor antagonist SB-649868 (10 or 30 mg) and a positive control zolpidem (10 mg), an allosteric modulator of GABA(A) receptors. Objective and subjective sleep parameters and next-day performance were assessed in 51 healthy male volunteers in a traffic noise model of situational insomnia. Compared with placebo, SB-649868 10

Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist. The orexin system plays a major role in the integration of metabolic and circadian influences that drive wakefulness. This paper describes initial Phase I trials of a novel dual orexin receptor antagonist SB-649868 that has demonstrated preclinical potential for treatment of sleep disorders. The trial designs included a single ascending dose escalation study (dose range: 10-80 mg in the fed and fasted states) and a multiple repeat dose study (dose range: 5-30 mg in the fed state) enrolling a total of 103 male volunteer subjects. SB-649868 was well tolerated at all doses in this study population, with mechanism-related adverse events (e.g. somnolence and fatigue

with the dual OX1/2R antagonist SB-649868 (30 mg/kg po) only partially attenuated the increase of ACTH. To assess whether the intrinsic and distinct sleep-promoting properties of each antagonist could account for the differential stress response, a separate group of mice implanted with electrodes for standard sleep recording were orally dosed with JNJ-42847922 or SB-649868 during the light phase. While both

-methylpiperidin-2-yl]methyl-pyridin-2-amine), a selective OX(1)R antagonist, JNJ-10397049 (N-(2,4-dibromophenyl)-N'-[(4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl]urea), a selective OX(2)R antagonist, and SB-649868 (N-[((2S)-1-{[5-(4-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]carbonyl}-2-piperidinyl)methyl]-1-benzofuran-4-carboxamide), a dual OX(1)/OX(2)R antagonist were evaluated in a binge eating (BE) model blocks BE in rats and humans. Dose-related thresholds for sleep-inducing effects of the OXR antagonists were measured using polysomnography in parallel experiments. SB-649868 and GSK1059865, but not JNJ-10397049, selectively reduced BE for HPF without affecting standard food pellet intake, at doses that did not induce sleep. These results indicate, for the first time, a major role of OX(1)R mechanisms

To Evaluate The Effects Of SB-649868 (10, 30 Mg And 60 Mg) On Subjects With Primary Insomnia To Evaluate The Effects Of SB-649868 (10, 30 Mg And 60 Mg) On Subjects With Primary Insomnia - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy record managers: refer to the Data Element reached the maximum number of saved studies (100).Please remove one or more studies before adding more. To Evaluate The Effects Of SB-649868 (10, 30 Mg And 60 Mg) On Subjects With Primary Insomnia The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our

. Bettica P, Squassante L, Zamuner S, Nucci G, Danker-Hopfe H, Ratti E. The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia. Sleep. 2012 Aug 1;35(8):1097-104. doi: 10.5665/sleep.1996. Herring WJ, Snyder E, Budd K, Hutzelmann J, Snavely D, Liu K, Lines C, Roth T, Michelson D. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial

Contacts and Locations More Information Brief Summary: The purpose of this study is to define the absorption, breakdown and excretion of a single dose of radiolabelled SB-649868 and its breakdown products by measuring their concentration in blood, urine and faeces over a 7-10 day period. "Radiolabelled" means that the test drug has a radioactive component to help us track the drug. The safety oral dose of 14C-SB649868 (containing approximately 70 microcuries of radiocarbon and 30 milligrams of SB649868). Drug: 14C-SB649868SB-649868 will be provided as powder in a bottle which will be reconstituted into a solution prior to dosing via a hard gelatin capsule. Each subject will receive one unit dose of SB-649868 30 milligram reconstituted powder presented in a size 00 capsule once

A Clinical Study to Evaluate the Pharmacokinetic Profile of SB-649868 in Elderly and Female Population A Clinical Study to Evaluate the Pharmacokinetic Profile of SB-649868 in Elderly and Female Population - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy record managers: refer WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. A Clinical Study to Evaluate the Pharmacokinetic Profile of SB-649868 in Elderly and Female Population The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal

15-Day Repeated-Dose Study With SB-649868 And Its Interaction With CYP3A4 Isoenzyme In Healthy Male Subjects. 15-Day Repeated-Dose Study With SB-649868 And Its Interaction With CYP3A4 Isoenzyme In Healthy Male Subjects. - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy record managers Save this study WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. 15-Day Repeated-Dose Study With SB-649868 And Its Interaction With CYP3A4 Isoenzyme In Healthy Male Subjects. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been

Sleep Initiation and Maintenance Disorders Drug: Formulation A Drug: Formulation B Drug: Formulation C Drug: Formulation D Drug: Formulation E Drug: Formulation F Drug: Formulation G Phase 1 Detailed Description: A single-centre, open-label, randomized, single-dose, 6-way crossover study to investigate the pharmacokinetics, safety and tolerability of 6 different formulations of SB-649868 30 mg (Part A) and the effect of food on the selected formulation of SB-649868 pharmacokinetic (Part B) in healthy male volunteers Study Design Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Study Type : Interventional (Clinical Trial

Study to Investigate Safety, Tolerability, Pharmacokinetics and Cardiac Function After Repeat Doses of SB-649868 in Healthy-volunteers Study to Investigate Safety, Tolerability, Pharmacokinetics and Cardiac Function After Repeat Doses of SB-649868 in Healthy-volunteers - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization Login * Home * Search Results * Study Record DetailSaved Studies Save this study WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. Study to Investigate Safety, Tolerability, Pharmacokinetics and Cardiac Function After Repeat Doses of SB-649868 in Healthy-volunteers The safety and scientific validity of this study

A Single-centre Open Label Study to Investigate the Effect of Repeat Doses of SB-649868 on the Pharmacokinetics of Simvastatin and Atorvastatin in Healthy Male Volunteers. A Single-centre Open Label Study to Investigate the Effect of Repeat Doses of SB-649868 on the Pharmacokinetics of Simvastatin and Atorvastatin in Healthy Male Volunteers. - Full Text View - ClinicalTrials.gov Try * Linking to This Site * Terms and Conditions * Disclaimer * PRS Login * Home * Search Results * Study Record DetailSaved Studies Save this study WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. A Single-centre Open Label Study to Investigate the Effect of Repeat Doses of SB-649868 on the Pharmacokinetics of Simvastatin