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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
781
Oral tablet (30 mg and 10 mg), administered daily before bedtime
Oral tablet, administered daily before bedtime
Percentage of Participants Who Experienced Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase
Cataplexy is defined as a sudden loss of muscle tone while awake which prevents voluntary movement.
Time frame: From the first day of study treatment up to 12 months
Percentage of Participants Who Experienced Sleep Paralysis AEs During the DB Treatment Phase
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).
Time frame: From the first day of study treatment up to 12 months
Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase
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).
Time frame: From the first day of study treatment up to 12 months
Percentage of Participants Who Experienced Falls AEs During the DB Treatment Phase
Falls were adjudicated (to establish whether a fall event was due to cataplexy).
Time frame: From the first day of study treatment up to 12 months
Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase
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.
Time frame: From the first day of study treatment up to 12 months
Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase
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.
Time frame: From the first day of study treatment up to 12 months
Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
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.
Time frame: From the first day of study treatment up to 12 months
Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)
Withdrawal effects assessed using Tyrer WSQ, which evaluated the presence/absence and severity of withdrawal symptoms with 20 items (i.e. sensitivity to noise, light, smell, touch, feeling unreal, etc). The Tyrer WSQ was completed as part of the evening e-diary prior to dosing on the Month 12 visit and on the 3 consecutive evenings of the DB Run-out Phase (first 3 nights of DB Discontinuation Phase). Responses rated 0 (No), 1 (Yes-moderate), or 2 (Yes-severe); range from 0 (no withdrawal) to 40 (severe withdrawal). A participant was defined to have a withdrawal symptom if an item during any of the 3 DB Run-out days had emerged for the first time, or had worsened compared to the measurement obtained at the end of the Treatment phase (Month 12). For single night analysis, a patient was defined to have withdrawal effects if the number of withdrawal symptoms (emergent or worsening) was ≥3. For across night analysis, withdrawal was defined as a total of ≥3 symptoms across the 3 nights.
Time frame: 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 Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase
Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia, and was assessed based on subjective total sleep time (sTST) as recorded in the participant's morning e-diary. A strict categorical analysis method (Yes/No) was used in which a participant was considered to have potentially experienced rebound (Yes) if the Morning Diary participant-reported sTST value (in minutes) on any of the 3 nights of the Run-out Phase (first 3 nights of the Discontinuation Phase) occurring after one year of treatment (Month 13) was less than the last value at baseline one year earlier (Month 1).
Time frame: Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13)
Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase
Rebound insomnia was defined as insomnia that occurred following discontinuation of a sedative substance taken to relieve primary insomnia, and was assessed based on subjective time to sleep onset (sTSO) as recorded in the participant's morning e-diary. A strict categorical analysis method (Yes/No) was used in which a participant was considered to have potentially experienced rebound (Yes) if the Morning Diary participant-reported sTSO value (in minutes) on any of the first 3 nights of the Run-out Phase occurring after one year of treatment (Month 13) was greater than the last value at baseline one year earlier (Month 1).
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Time frame: 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
The sTSTm was defined as the average over time of daily e-diary values for a participant's report of the total amount of time spent asleep before waking for the day (measured in minutes). Weekly sTSTm values (Week 1, Week 2, etc.) were the average of the daily e-diary values for the week. A summary value of this measure for Month 1 was obtained by taking the average of weekly sTSTm values for Weeks 1 through 4; (Week 1 + Week 2 + Week 3 + Week 4) ÷ 4. LS Mean Change from Baseline in sTSTm was then calculated at Week 1, Week 2, Week 3, Week 4, and Month 1.
Time frame: Baseline, Week 1, Week 2, Week 3, and Week 4
Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase
The sTSOm was defined as the average over time of daily e-diary values for a participant's report of the time he or she required to fall asleep (measured in minutes). Weekly sTSOm values (Week 1, Week 2, etc.) were the average of the daily e-diary values for the week. A summary value of this measure for Month 1 was obtained by taking the average of weekly sTSTm values for Weeks 1 through 4; (Week 1 + Week 2 + Week 3 + Week 4) ÷ 4. LS Mean Change from Baseline in sTSOm was then calculated at Week 1, Week 2, Week 3, Week 4, and Month 1.
Time frame: Baseline, Week 1, Week 2, Week 3, and Week 4