Phase IV 4 Way Crossover Study to Assess and Compare the Effect of a Single Nighttime Administration of Zolpidem, Silenor and Placebo on Arousability, Ataxia/Balance and Cognitive Performance in Healthy Volunteers.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Auditory Arousal Threshold (AAT) at T-max
研究概览
简要总结
This is a Phase IV, randomized, double-blind, placebo-controlled, four-arm crossover study. The study will assess the effects of a single dose of Silenor 6 mg compared with matching placebo and a single dose of zolpidem 10 mg compared to its matching placebo at the respective T-max in normal healthy adult male volunteers. The study will be conducted in approximately 52 male subjects
详细描述
Subjects will be screened and asked to complete sleep disorders questionnaires and a sleep diary to establish normal sleep patterns and to rule out any sleep disorder.
Eligible subjects will be scheduled for a Screening PSG to rule out PLMS, sleep apnea and other sleep disorders.
Subjects who meet the screening PSG criteria will be randomly assigned to a treatment sequence order that involves both the study drug and the time subjects are awakened in the middle-of-the-night using a crossover study design. These four sequences include Silenor 6 mg with a middle-of-the-night awakening at 4 hours (DXP-4H), zolpidem 10 mg with a middle-of-the-night awakening at 1.5 hours (ZOL-1.5H), placebo with a middle-of-the-night awakening at 4 hours (PBO-4H), and placebo with a middle-of-the-night awakening at 1.5 hours (PBO-1.5H). Study drug will be administered under fasted conditions (at least 4 hours) as a single dose at bedtime (approximately 2300 hours), and each subject will receive one dose of each active drug (Silenor 6 mg and zolpidem 10 mg), and two doses of placebo during the treatment period.
Safety assessments will be performed throughout the study.
During the night of assessment, subjects will be awoken at the estimated T-max of the active drugs, with a matching placebo group awakened at each of these time points with the same arousability protocol. Arousability will be assessed using the Auditory Awakening Threshold test (AAT) .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Be in good general health as determined by the investigator;
- •Have a 3-month history of a normal nightly sleep pattern based on the subject's self report ;
- •A usual time in bed
- •A regular bedtime between 2200 and 2400 hours
- •No habitual daytime napping;
- •Epworth Sleepiness Scale score ≤ 10;
- •Be able to read, understand, and provide written/dated informed consent before enrolling in the study, and must be willing and able to comply with all study procedures;
- •Be able to follow verbal and written instructions provided in English
排除标准
- •Have a body mass index (BMI) >35 kg/m2
- •Have symptoms consistent with the diagnosis of any sleep disorder (e.g., insomnia, sleep apnea, narcolepsy, periodic leg movements, or restless leg syndrome);
- •On screening PSG AHI > 10 or PLMAI >10;
- •Have a known or suspected diagnosis of Acquired Immune Deficiency Syndrome (AIDS), or have tested seropositive for human immunodeficiency virus (HIV) antibody or antigen previously;
- •Have any clinically significant abnormal finding in physical examination, neurological assessment, vital signs, elevated body temperature, or clinical laboratory tests, as determined by the Investigator;
- •Have a known exaggerated pharmacological sensitivity, hypersensitivity, or history of a clinically significant adverse reaction to zolpidem;
- •Have a known or exaggerated pharmacological sensitivity, hypersensitivity, or intolerance to doxepin HCl, any tricyclic antidepressant, or antihistamine;
- •Currently taking cimetidine or a monoamine oxidase inhibitor (MAOI);
- •Current diagnosis of severe urinary retention;
- •Current diagnosis of untreated glaucoma;
- •Intends to use any medication including over-the-counter (OTC) medications that would interfere with normal sleep architecture (such as systemic steroids, beta-adrenergic blockers, amphetamines, modafinil, etc.);
- •Self-reports use of products containing nicotine of greater than 15 cigarettes daily, or cannot avoid products containing nicotine during the normal sleep periods;
- •Self report consumption of more than five alcoholic beverages on any one day or greater than 14 alcoholic beverages weekly over the past week;
- •Have a history of epilepsy or serious head injury;
- •Used CYP450 2D6 inducers or inhibitors within 7 days before screening;
- •Have used prescribed or OTC medications within 30 days of screening (Day 0) or intend to use any prescription or OTC medication during the study that may interfere with the evaluation of the study drug.
- •Have used an investigational drug within 30 days or five half lives (whichever is longer) before screening, or plans to use an investigational drug during the study or have used doxepin or zolpidem previously.
- •Score of < 40 on the BBS at screening
研究组 & 干预措施
Placebo (PBO-4H)
placebo single nightime dose -4 hour post dose arousability and cognitive assessments
干预措施: Placebo (Drug)
Silenor 6 mg (DXP-4H)
Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments
干预措施: Silenor 6 mg (Drug)
Silenor 6 mg (DXP-4H)
Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments
干预措施: zolpidem 10 mg (Drug)
Silenor 6 mg (DXP-4H)
Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments
干预措施: Placebo (Drug)
Placebo (PBO-4H)
placebo single nightime dose -4 hour post dose arousability and cognitive assessments
干预措施: Silenor 6 mg (Drug)
Placebo (PBO-4H)
placebo single nightime dose -4 hour post dose arousability and cognitive assessments
干预措施: zolpidem 10 mg (Drug)
Zolpidem 10 mg (ZOL-1.5H)
zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments
干预措施: Silenor 6 mg (Drug)
Zolpidem 10 mg (ZOL-1.5H)
zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments
干预措施: zolpidem 10 mg (Drug)
Zolpidem 10 mg (ZOL-1.5H)
zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments
干预措施: Placebo (Drug)
Placebo (PBO-1.5H)
placebo single nightime dose -1.5 hour arousability and cognitive assessments
干预措施: Silenor 6 mg (Drug)
Placebo (PBO-1.5H)
placebo single nightime dose -1.5 hour arousability and cognitive assessments
干预措施: zolpidem 10 mg (Drug)
Placebo (PBO-1.5H)
placebo single nightime dose -1.5 hour arousability and cognitive assessments
干预措施: Placebo (Drug)
结局指标
主要结局
Auditory Arousal Threshold (AAT) at T-max
时间窗: at either 1.5 or 4 hours post dose
AAT will performed at T-max for Silenor and matching placebo at 4 hours post dose. Assessments performed at t max for zolpidem and placebo at 1.5 hours post dose. An acoustic stimulus (1000 Hz tone) was presented through audiometric earphones (E-A-RTone 3A Insert Earphones). Tones began at 30 dB and increased by 5 dB until the participant woke up or the maximum dB-level (110 dB) was reached.
次要结局
- Tandem Walk Step-Offs(at either 1.5 or 4 hours post dose)
- Tandem Walk Duration Over Five Trials(at either 1.5 or 4 hours post dose)
- Immediate Free Recall Task(directly after the encoding task)
- Delayed Free Recall Task(15 minutes after final awakening the morning)
- Berg Balance Test(at either 1.5 or 4 hours post dose)
- Number of Participants With Adverse Events(throughout the study until the final study visit, up to 6 weeks)