A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Long Term Safety Study of MK-4305 in Patients With Primary Insomnia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 781
- 主要终点
- Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase
研究概览
简要总结
This study will establish the safety and tolerability of suvorexant (MK-4305) when administered for up to 14 months. Participants will be randomized to receive suvorexant or placebo for a 12-month double-blind (DB) Treatment Phase. Participants who complete the 12-month DB Treatment Phase will enter a 2-month DB Randomized Discontinuation Phase. At the time of initial randomization, participants assigned to receive suvorexant during the initial 12-month Treatment Phase will be simultaneously randomized, in a 1:1 ratio, to receive either suvorexant or placebo during the 2-month Randomized Discontinuation Phase. Participants randomized to receive placebo in the initial 12-month Treatment Phase will continue to receive placebo during the 2-month Randomized Discontinuation Phase.
The first 3 nights of the Randomized Discontinuation Phase are referred to as the Run-Out Phase, and will assess rebound and withdrawal.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of primary insomnia
- •Participant is able to read, understand, and complete questionnaires and diaries
- •If female, participant and partner both agree to use acceptable contraception. If male partner does not use an effective form of contraception, female participant must use 2 acceptable forms of contraception
- •If ≥65 years of age, score of ≥25 on the Mini Mental State Examination (MMSE)
排除标准
- •If female, participant is pregnant
- •Participant expects to donate eggs or sperm during the study
- •Recent and/or active history of a confounding neurological disorder
- •History of clinically unstable cardiovascular disorder within the last 6 months
- •Lifetime history of bipolar disorder
- •Psychiatric condition that requires treatment with a medication prohibited by the study, or any other psychiatric condition that would interfere with the participant's ability to participate in the study
- •History of substance abuse/dependence
- •History of cancer ≤5 years prior to study participation except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
- •Evidence of suicidality (based on a score of 2 on the Quick Inventory of Depressive Symptomatology Self-Report 16-Item ([QIDS-SR16] suicide item #12)
- •Participant has travelled across >3 time zones or >3 hour time difference in the last 2 weeks
- •History of permanent night shift work or rotating day/night shift work in the past 2 weeks
- •Body Mass Index (BMI) >40 kg/m^2
研究组 & 干预措施
Suvorexant
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the Treatment Phase.
干预措施: Suvorexant (Drug)
Suvorexant
After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the Treatment Phase.
干预措施: Dose-matched Placebo to Suvorexant (Drug)
Placebo
After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the Treatment Phase.
干预措施: Dose-matched Placebo to Suvorexant (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase
时间窗: From the first day of study treatment up to 12 months
Complex sleep-related behaviors were reported as ECIs and were characterized by patients engaging in specific activities while asleep (e.g., eating, drinking, preparing meals, making phone calls, having sex, driving, and sleep walking).
Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
时间窗: From the first day of study treatment up to 12 months
The pre-specified terms which were suggestive of abuse potential on this study included depersonalization (feeling of watching oneself act, while having no control over a situation), derealization (alteration in the perception or experience of the external world so that it seems unreal), dissociation (includes a wide array of experiences from mild detachment from immediate surroundings to more severe detachment from physical and emotional experience), euphoric mood (exaggerated feeling of physical and emotional well-being and optimism not consonant with apparent stimuli or events), mania (state of abnormally elevated or irritable mood, arousal, and/or energy levels), hallucination (perception in the absence of a stimulus which has qualities of real perception), and potential study medication misuse.
Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase
时间窗: From the first day of study treatment up to 12 months
Suicidal ideation included suicidal plans, suicidal tendency, death wishes, life weariness, and suicidal intention. Suicidal behaviors included suicide attempts, suicide gesture, and self-injurious behaviour. Suicidal ideation and/or behavior was reported as an AE and considered an ECI.
Percentage of Participants Who Experienced Sleep Paralysis AEs During the DB Treatment Phase
时间窗: From the first day of study treatment up to 12 months
Sleep paralysis was defined as the inability to perform voluntary muscle movements during sleep. Sleep paralysis adverse events included sleep-onset paralysis (paralysis as one is falling asleep).
Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase
时间窗: From the first day of study treatment up to 12 months
Perceptual distortions associated with transitions between wakefulness and sleep were termed as hypnagogic (occurring during the onset of sleep) or hypnopompic (occurring during onset of wakefulness) hallucinations.
Percentage of Participants Who Experienced Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase
时间窗: From the first day of study treatment up to 12 months
Cataplexy is defined as a sudden loss of muscle tone while awake which prevents voluntary movement.
Percentage of Participants Who Experienced Falls AEs During the DB Treatment Phase
时间窗: From the first day of study treatment up to 12 months
Falls were adjudicated (to establish whether a fall event was due to cataplexy).
次要结局
- Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase(Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13))
- Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase(Baseline, Week 1, Week 2, Week 3, and Week 4)
- Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)(Evening of Month 12 visit and next 3 consecutive days (Night 1, 2, and 3 of Discontinuation Phase [otherwise known as the Run-out]))
- Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase(Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13))
- Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase(Baseline, Week 1, Week 2, Week 3, and Week 4)