Dataset Information

On-the-Road Driving Performance the Morning after Bedtime Use of Suvorexant 20 and 40 mg: A Study in Non-Elderly Healthy Volunteers.

ABSTRACT: To evaluate next-morning driving performance in adults younger than 65 years, after single and repeated doses of suvorexant 20 and 40 mg.Double-blind, placebo-controlled, 4-period crossover study.Maastricht University, The Netherlands.28 healthy volunteers (15 females), aged 23 to 64 years.Suvorexant (20 and 40 mg) for 8 consecutive nights; zopiclone 7.5 mg nightly on day 1 and 8; placebo.Performance on day 2 and 9 (9 h after dosing) using a one-hour standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo changes in SDLP > 2.4 cm were considered to reflect meaningful driving impairment.Mean drug-placebo changes in SDLP following suvorexant 20 and 40 mg were 1.01 and 1.66 cm on day 2, and 0.48 and 1.31 cm on Day 9, respectively. The 90% CIs of these changes were all below 2.4 cm. Symmetry analysis showed that more subjects had SDLP changes > 2.4 cm than < -2.4 cm following suvorexant 20 and 40 mg on day 2, and following suvorexant 40 mg on day 9. Four female subjects requested that a total of 5 driving tests--all following suvorexant--stop prematurely due to self-reported somnolence.As assessed by mean changes in standard deviation of lateral position (SDLP), there was no clinically meaningful residual effect of suvorexant in doses of 20 and 40 mg on next-morning driving (9 h after bedtime dosing) in healthy subjects < 65 years old. There may be some individuals who experience next-day effects, as suggested by individual changes in SDLP and prematurely stopped tests.clinicaltrials.gov NCT01311882.

SUBMITTER: Vermeeren A

PROVIDER: S-EPMC4813357 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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On-the-Road Driving Performance the Morning after Bedtime Use of Suvorexant 20 and 40 mg: A Study in Non-Elderly Healthy Volunteers.

Vermeeren Annemiek A Sun Hong H Vuurman Eric F P M EF Jongen Stefan S Van Leeuwen Cees J CJ Van Oers Anita C M AC Palcza John J Li Xiadong X Laethem Tine T Heirman Ingeborg I Bautmans An A Troyer Matthew D MD Wrishko Rebecca R McCrea Jacqueline J

Sleep 20151101 11

<h4>Study objective</h4>To evaluate next-morning driving performance in adults younger than 65 years, after single and repeated doses of suvorexant 20 and 40 mg.<h4>Design</h4>Double-blind, placebo-controlled, 4-period crossover study.<h4>Setting</h4>Maastricht University, The Netherlands.<h4>Participants</h4>28 healthy volunteers (15 females), aged 23 to 64 years.<h4>Interventions</h4>Suvorexant (20 and 40 mg) for 8 consecutive nights; zopiclone 7.5 mg nightly on day 1 and 8; placebo.<h4>Measur ...[more]

PMID: 26039969

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Project description:BACKGROUND:We report on the results of a Japanese postmarketing drug-use survey of suvorexant (Belsomra®) tablets. METHODS:A survey with a ??6-month observation period after the start of administration was conducted, targeting insomnia patients who were treated with suvorexant for the first time in Japan. Information on the safety and efficacy of the drug product was collected. The evaluation period was July 21, 2015-August 12, 2017, and the target number of patients was 3428. RESULTS:The mean administration period for the safety analysis population of 3248 patients was 113 days. At 6 months after the start of treatment, 48.6% (1577/3248) of the patients had been continually receiving treatment, and 51.4% (1671/3248) of the patients discontinued/dropped out of treatment before 6 months. Among the patients who discontinued/dropped out of the treatment, more than 30% discontinued due to improvement. The mean treatment duration for those who had discontinued treatment for this reason was 62 days. The incidence rate of adverse drug reactions among those in the safety analysis population was 9.7%, and the common adverse drug reactions were somnolence (3.6%), insomnia (1.2%), dizziness (1.1%), and nightmare (0.8%), all of which are described in the product label. No additional noteworthy events were observed. In 2439 patients with a final overall global assessment of sleep judged by physicians, the 'improved' rate was 74.0%. Among 2424 patients who provided a final overall global assessment, the improvement rate was 73.2%, which was comparable with the improvement rate judged by physicians. Regarding clinical effects (based on patient diary data or physician's assessment), reduction in median sleep latency and increase in median total sleep time (reduction from 60 to 50 min and increase from 300 to 360 min compared with baseline, respectively) were observed at 1 week after the start of treatment and onwards, and the effect was maintained after the start of treatment for 6 months. A similar effect was observed irrespective of age groups or reasons for using suvorexant. CONCLUSION:This survey was an exploratory observational study without a control group; the interpretation of results may require the consideration of factors that may have caused bias in the results, such as demographic characteristics and effects of other drugs. However, the results suggest that suvorexant can be a useful drug in daily clinical practice for treating insomnia.

Project description:Study objectivesThe chronic pain disorder, fibromyalgia, is associated with sleep disturbance, typically sleep maintenance. No studies have evaluated the effect of sleep medication on pain sensitivity in this population. Suvorexant, an orexin antagonist approved for treatment of insomnia, was evaluated for effects on both sleep and the pain of fibromyalgia.MethodsWomen age 21 to 65 years with fibromyalgia and comorbid insomnia (n = 10) were treated, double-blind, for 9 nights each with suvorexant, 20 mg and placebo in counterbalanced order. All were in good psychiatric and stable physical health and met American College of Rheumatology 2010 criteria for fibromyalgia and Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition criteria for insomnia. Screening 8-hour polysomnography (PSG) was used to rule out other sleep disorders. On nights 8 and 9 of each treatment 8-hour PSG were collected and on days 1 and 8 pain sensitivity was assessed at 1100 and 1500 hours by measuring finger withdrawal latency (FWL) to a radiant heat stimulus at 5 randomly presented intensity levels.ResultsSuvorexant versus placebo increased total sleep time (7.2 versus 6.7 hours, P < .05) and reduced wake after sleep onset (37 versus 67 minutes, P < .04) with no night effects or interaction. Latency to persistent sleep and sleep stage measures were not altered. FWL on both am and pm tests varied as a function of intensity (P < .001). Average FWL (over 5 intensities and both days) was increased relative to placebo on both the am (13.9 versus 13.1 seconds) and pm tests (15.8 versus 14.1 seconds, P < .03) following suvorexant the previous night.ConclusionsSuvorexant 20 mg in patients with fibromyalgia, improved sleep time and reduced next-day pain sensitivity on assessments of FWL to a radiant heat stimulus.Clinical trial registryRegistry: ClinicalTrials.gov; Name: A double-blind cross-over, study to compare the hypnotic, daytime sleepiness/fatigue, and pain effects of nighttime administration of suvorexant 20 mg versus placebo in patients with fibromyalgia and comorbid insomnia; Identifier: NCT02684136; URL: https://clinicaltrials.gov/ct2/show/NCT02684136.

Project description:BackgroundEsomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol DR), was developed to extend the duration of gastric acid suppression.PurposeThis study aimed to evaluate the pharmacokinetics (PKs) and pharmacodynamics (PDs) of esomeprazole for the DR formulation compared to a conventional enteric-coated (EC) formulation (Nexium) in healthy male subjects.MethodsTwo randomized, open-label, multiple-dose, two-way crossover studies with esomeprazole 20 mg and 40 mg were conducted. Subjects received the DR formulation or the EC formulation once daily for 7 days in each period with a 7-day washout. Serial blood samples were collected up to 24 hours after the 1st dose, and 24-hour intragastric pH was continuously monitored before the 1st dose as baseline and after the 1st and the 7th dose.ResultsIn 20 mg and 40 mg dose groups, 38 and 44 subjects completed the study, respectively. The DR formulation exhibited the dual-release pattern of esomeprazole, resulting in more sustained plasma concentration-time profiles compared to the EC formulation. The systemic exposure of esomeprazole for the DR formulation was comparable to that for the EC formulation, showing the similar area under the plasma concentration-time curve. The 24-hour gastric acid suppression was also similar between the two formulations, while the inhibition during night-time (22:00-06:00) showed a better tendency in the DR formulation.ConclusionThe sustained exposure of esomeprazole in the DR formulation led to well-maintained and higher acid inhibition compared to the EC formulation, especially during the night-time. These results suggest that the DR formulation can be an alternative formulation to the conventional EC formulation, expecting the potential of relieving nocturnal acid-related symptoms.

Project description:UnlabelledThe present study aimed to investigate the pharmacokinetic properties of febuxostat in healthy Chinese male volunteers and evaluate whether the two formulations of febuxostat 40-mg and 80-mg tablets are bioequivalent. A randomized, open-label, 4-way crossover study was conducted in healthy Chinese male volunteers under fasting conditions. 24 eligible subjects were randomized in a 1:1:1:1 ratio to receive a single dose of test or reference formulation of febuxostat 40-mg or 80-mg tablet. The washout period between each administration was 1 week. Plasma febuxostat was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests. After single-dosing of 1 tablet of 40-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.22±0.87 and 1.85±1.03 h, Cmax 1689.16±461.31 and 1613.80±608.43 ng·mL-1, AUC0-t 5139.87±1349.28 and 5517.91±2024.26 ng·mL-1·h, AUC0-∞ 5263.06±1339.16 and 5640.48±2040.22 ng·mL-1·h, t1/2 4.82±2.61 and 4.85±1.78 h, respectively. After single-dosing of 1 tablet of 80-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.71±1.21 and 2.23±1.55 h, Cmax 2744.47±1157.44 and 2998.17±1200.13 ng·mL-1, AUC0-t 9634.03±2768.25 and 10467.95±3501.65 ng·mL-1·h, AUC0-∞ 9834.32±2730.51 and 10626.63±3504.08 ng·mL-1·h, t1/2 6.25±2.44 and 5.46±1.65 h, respectively. For single-dosing of 1 tablet of 40-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 89.79 to 102.55, 90.14 to 102.56 and 93.99 to 129.63, respectively. For single-dosing of 1 tablet of 80-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 86.67 to 100.00, 87.50 to 100.51 and 79.48 to 105.99, respectively. This single dose study revealed similar pharmacokinetic properties in healthy Chinese male volunteers as those found in Caucasic population. The test and reference febuxostat tablets formulations met the regulatory criteria for bioequivalence at 40-mg and 80-mg strengths in fasting healthy Chinese male volunteers.Trial registrationChictr.org ChiCTR-TTRCC-14004288.

Dataset Information

On-the-Road Driving Performance the Morning after Bedtime Use of Suvorexant 20 and 40 mg: A Study in Non-Elderly Healthy Volunteers.

Publications

On-the-Road Driving Performance the Morning after Bedtime Use of Suvorexant 20 and 40 mg: A Study in Non-Elderly Healthy Volunteers.

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