A Multicenter, Randomized, Double-Mask, Placebo-Controlled, Parallel Study to Investigate the Efficacy and Safety of 20 mg Tasimelteon Versus Placebo in Totally Blind Subjects With N24HSWD Followed by an OLE Phase
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 28
- 主要终点
- Proportion of Patients Entrained as Assessed by Urinary aMT6
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of a six month double-mask treatment of tasimelteon or placebo in male and female subjects with Non-24-Hour Sleep-Wake Disorder
详细描述
Non-24-Hour Sleep-Wake Disorder (N24HSWD) occurs when individuals, primarily those without light perception, are unable to synchronize their endogenous circadian pacemaker to the 24-hour light-dark cycle, and the timing of their circadian rhythm instead reflects the intrinsic period of their endogenous circadian pacemaker. As a result, the circadian rhythm of sleep-wake propensity in these individuals moves gradually later and later each day if there circadian period is > 24 hours and earlier and earlier if < 24 hours. These individuals will be able to sleep well at night when their sleep-wake propensity rhythm is approximately aligned with the 24-hour light-dark and social cycle. However, after a short time, the endogenous sleep-wake propensity rhythm and the 24-hour light-dark cycle will move out of synchrony with each other, and they may have difficulty falling asleep until well into the night. In addition to problems sleeping at the desired time, the subjects experience daytime sleepiness and daytime napping.
This will be a multicenter, randomized, double-masked, placebo-controlled, parallel study. The study has two phases: the pre-randomization phase followed by either the randomization phase or the open-label extension (OLE). The pre-randomization phase comprises a screening visit where subject's initial eligibility will be evaluated, a circadian period (τ) estimation segment, and a variable-length in-phase transition segment in which subjects will wait to start treatment until their circadian phase is aligned with their target bedtime. Subjects that meet all entry criteria for the study will enter the randomization phase. During the randomization phase, subjects will be asked to take either 20 mg tasimelteon or placebo approximately 1 hour prior to their target bedtime for 26 weeks in a double-masked fashion. Subjects who have a τ greater than 24.0 and meet all entry criteria but that are ineligible for the randomization phase due to their τ estimate may be given the opportunity to participate in the OLE phase. During the OLE phase, subjects will take open-label 20mg tasimelteon for 26 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability and acceptance to provide informed consent;
- •No perception of light by the subject's own report;
- •Diagnosis of N24HSWD as determined by:
- •History (within the last 3 months) of trouble sleeping at night difficulty initiating sleep or staying asleep), difficulty awakening in the morning, or daytime sleepiness as determined by answering yes to at least one question in the Sleep Complaint Questionnaire and
- •Urinary aMT6s demonstrates a progressive delay of the aMT6 acrophase time.
- •Willing and able to comply with study requirements and restrictions including a commitment to a fixed 9-hour sleep opportunity during the study;
- •Fluent in English;
排除标准
- •Have a probable diagnosis of a current sleep disorder other than N24HSWD that is the primary cause of the sleep disturbance based on clinical investigator medical judgment;
- •Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled and stable;
- •History (within the 12 months prior to screening) of psychiatric disorders including Major Depressive Disorder, Generalized Anxiety Disorder, Axis II Disorders, delirium or any other psychiatric disorder that in the opinion of the clinical investigator would affect participation in the study or full compliance with study procedures;
- •History of intolerance and/or hypersensitivity to melatonin or melatonin agonists;
- •Worked night, rotating, or split (period of work, followed by break, and then return to work) shift work within 1 month of the screening visit or plan to work these shifts during the study;
- •Unable to perform calls to the study IVR system to report questionnaire results;
- •Exposure to any investigational drug, including placebo, within 30 days or 5 half lives (whichever was longer) of screening;
- •Use of central nervous system prescription or OTC medications, other than melatonin, that affects the sleep-wake cycle
- •Use of melatonin or melatonin agonist
研究组 & 干预措施
tasimelteon
20 mg tasimelteon capsules, PO daily for 6 months
干预措施: tasimelteon (Drug)
placebo
Placebo capsules, PO daily for 6 months
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of Patients Entrained as Assessed by Urinary aMT6
时间窗: 1 month
Entrainment is a measure of synchronization of the master body clock to the 24-hour day. The circadian period (τ) was calculated using urinary aMT6s collected over four 48 hour periods , collected approximately 1 week apart for 4 separate weeks, during the screening and month 1 of the randomization phase of the trial. Entrainment was defined as having a post-baseline τ value less than 24.1 and a 95% CI that included 24.0.
Proportion of Patients With a Clinical Response: Entrainment of aMT6 and Score of ≥ 3 on N24CRS
时间窗: 6 months
Clinical response is defined as the coincident demonstration of entrainment (aMT6) and a score ≥ 3 on the Non-24 Clinical Response Scale (N24CRS). N24CRS measures improvement in sleep-wake measures and overall functioning (LQ-nTST, UQ-dTSD, MoST and CGI-C). Each assessment is scored as a 1 or 0 depending on the pre-specified threshold (see below). LQ-nTST: \>45 minutes increase in average nighttime sleep duration; UQ-dTSD: \>45 minutes decrease in average daytime sleep duration; MoST: \>30 minutes increase and a standard deviation \<2 hours during double-masked phase (6 months); CGI-C: \<2.0 from the average of D112 and Day 183 compared to baseline For patients randomized to tasimelteon 20 mg and who also participated in the screening phase of Study 3203 (month 7 of treatment), the screening τ from Study 3203 was used if the patient did not become entrained in Study 3201 but did become entrained during the screening phase of Study 3203.
次要结局
- Proportion of Patients Entrained as Assessed by Urinary Cortisol(1 month)
- Average Clinical Global Impression of Change (CGI-C)(Day 112 and 183)
- Proportion of Responders With a Combined Sleep/Wake Response for LQ-nTST (≥ 90 Minutes) and UQ-dTSD (≤ 90 Minutes)(6 months)
- Average Lower Quartile of Nights of Nighttime Total Sleep Time (LQ-nTST)(6 months)
- Average Midpoint of Sleep (MoST)(6 months)
- Average Upper Quartile of Days of Subjective Daytime Sleep Duration (UQ-dTSD)(6 months)
- Number of Patients With a Treatment Emergent Adverse Event (Open Label Extension Phase Only)(6 months)