Insomnia
Conditions
Brief summary
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.
Interventions
DRUGSuvorexant
Oral tablet (30 mg and 10 mg), administered daily before bedtime
Oral tablet, administered daily before bedtime
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | 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 Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase | 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 Sleep Paralysis AEs During the DB Treatment Phase | 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 Complex Sleep-related Behaviors AEs During the DB Treatment Phase | 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 Falls AEs During the DB Treatment Phase | From the first day of study treatment up to 12 months | Falls were adjudicated (to establish whether a fall event was due to cataplexy). |
| Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase | 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 Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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]) | 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. |
| 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) | 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). |
| 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) | 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). |
| 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 | 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. |
| 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Reported Suicidal Ideation and/or Behavior On Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS) | From the first day of study treatment through study follow-up (up to 14 months) | Suicidal ideation and/or behavior that occurred on study was also assessed using the C-SSRS, a rater-administered questionnaire used to prospectively assess suicidal ideation and suicidal behavior. C-SSRS assessment was based upon a clinician's interpretation of the participant's responses to the C-SSRS questions, not by a numbered scale. Suicidal ideation and/or behaviors identified on the C-SSRS may not have been considered an adverse event, based on the investigator's judgment. |
Participant flow
Pre-assignment details
Of the 781 participants randomized into the Treatment Phase, 522 were randomized to suvorexant and 259 were randomized to placebo. Two participants were randomized, but not treated (one from each treatment group); therefore, the total number of participants evaluated for safety was 779.
Participants by arm
| Arm | Count |
|---|---|
| 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 double-blind (DB) Treatment Phase. | 521 |
| 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 DB Treatment Phase. | 258 |
| Total | 779 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| DB Randomized Discontinuation Phase | Adverse Event | 0 | 0 | 0 | 3 | 1 |
| DB Randomized Discontinuation Phase | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 |
| DB Randomized Discontinuation Phase | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| DB Randomized Discontinuation Phase | Protocol Violation | 0 | 0 | 1 | 0 | 0 |
| DB Randomized Discontinuation Phase | Withdrawal by Subject | 0 | 0 | 3 | 1 | 3 |
| DB Treatment Phase | Adverse Event | 60 | 22 | 0 | 0 | 0 |
| DB Treatment Phase | Lack of Efficacy | 44 | 28 | 0 | 0 | 0 |
| DB Treatment Phase | Lost to Follow-up | 14 | 12 | 0 | 0 | 0 |
| DB Treatment Phase | Physician Decision | 17 | 8 | 0 | 0 | 0 |
| DB Treatment Phase | Pregnancy | 1 | 0 | 0 | 0 | 0 |
| DB Treatment Phase | Protocol Violation | 4 | 3 | 0 | 0 | 0 |
| DB Treatment Phase | Withdrawal by Subject | 60 | 24 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Suvorexant | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 14.5 | 62.0 years STANDARD_DEVIATION 14.6 | 61.5 years STANDARD_DEVIATION 14.5 |
| Mean Subjective Time to Sleep Onset in minutes (sTSOm) | 65.9 minutes STANDARD_DEVIATION 63.8 | 65.0 minutes STANDARD_DEVIATION 60.6 | 65.6 minutes STANDARD_DEVIATION 62.7 |
| Mean Subjective Total Sleep Time (sTSTm) | 320.4 minutes STANDARD_DEVIATION 76.1 | 329.9 minutes STANDARD_DEVIATION 79.4 | 323.5 minutes STANDARD_DEVIATION 77.3 |
| Sex: Female, Male Female | 287 Participants | 149 Participants | 436 Participants |
| Sex: Female, Male Male | 234 Participants | 109 Participants | 343 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 184 / 521 | 63 / 258 | 7 / 156 | 5 / 166 | 9 / 162 | 2 / 260 | 1 / 261 | 2 / 258 |
| serious Total, serious adverse events | 27 / 521 | 17 / 258 | 3 / 156 | 1 / 166 | 1 / 162 | 1 / 260 | 0 / 261 | 2 / 258 |
Outcome results
Primary
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
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suvorexant | Percentage of Participants Who Experienced Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase | 0.0 percentage of participants |
Primary
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
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Suvorexant | Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase | any complex sleep-related behaviors | 0.2 percentage of participants |
| Suvorexant | Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase | somnambulism | 0.2 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase | any complex sleep-related behaviors | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase | somnambulism | 0.0 percentage of participants |
Comparison: The method of Miettinen and Nurminen was used to construct the confidence interval for the difference in the percentage of participants with any complex sleep-related behaviors AEs between the Suvorexant group and Placebo group.p-value: 0.48295% CI: [-1.3, 1.1]Miettinen & Nurminen Method.
Primary
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
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suvorexant | Percentage of Participants Who Experienced Falls AEs During the DB Treatment Phase | 2.3 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Falls AEs During the DB Treatment Phase | 3.1 percentage of participants |
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and construct the confidence interval for the difference in the percentage of participants with any falls AEs between the Suvorexant group and Placebo group.p-value: 0.50895% CI: [-3.9, 1.5]Miettinen & Nurminen Method
Primary
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
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Suvorexant | Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase | Hypnagogic hallucination | 0.6 percentage of participants |
| Suvorexant | Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase | Any hypnagogic/hypnopompic hallucinations AEs | 0.8 percentage of participants |
| Suvorexant | Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase | Hypnopompic hallucination | 0.2 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase | Any hypnagogic/hypnopompic hallucinations AEs | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase | Hypnagogic hallucination | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase | Hypnopompic hallucination | 0.0 percentage of participants |
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and construct the confidence interval for the difference in the percentage of participants with any Hypnagogic/hypnopompic hallucinations AEs between the Suvorexant group and Placebo group.p-value: 0.15995% CI: [-0.7, 2]Miettinen & Nurminen Method
Primary
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
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Suvorexant | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Hypnopompic hallucination | 0.2 percentage of participants |
| Suvorexant | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Derealisation | 0.2 percentage of participants |
| Suvorexant | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | any selected AE of potential abuse | 3.5 percentage of participants |
| Suvorexant | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Drug maladministration | 2.3 percentage of participants |
| Suvorexant | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Hallucination, auditory | 0.2 percentage of participants |
| Suvorexant | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Hallucination, visual | 0.2 percentage of participants |
| Suvorexant | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Hypnagogic hallucination | 0.6 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | any selected AE of potential abuse | 3.9 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Hallucination, auditory | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Hypnopompic hallucination | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Hypnagogic hallucination | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Hallucination, visual | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Drug maladministration | 3.9 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase | Derealisation | 0.0 percentage of participants |
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and construct the confidence interval for the difference in the percentage of participants with any selected AEs associated with potential abuse between the Suvorexant group and Placebo group.p-value: 0.76795% CI: [-3.8, 2.2]Miettinen & Nurminen Method
Primary
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
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suvorexant | Percentage of Participants Who Experienced Sleep Paralysis AEs During the DB Treatment Phase | 0.4 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Sleep Paralysis AEs During the DB Treatment Phase | 0.0 percentage of participants |
Comparison: The method of Miettinen and Nurminen was used to construct the confidence interval for the difference in the percentage of participants with any sleep paralysis AEs between the Suvorexant group and Placebo group .95% CI: [-1.1, 1.4]Miettinen & Nurminen Method.
Primary
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
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suvorexant | Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase | 0.8 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase | 0.0 percentage of participants |
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and construct the confidence interval for the difference in the percentage of participants with any suicidal ideation/behavior AEs considered an ECI between the Suvorexant group and Placebo group.p-value: 0.15995% CI: [-0.7, 2]Miettinen & Nurminen Method
Secondary
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
Population: Full Analysis Set (FAS)-Efficacy; all randomized participants who had ≥1 post-randomization observation for the analysis endpoint subsequent to ≥1 dose of study treatment, and baseline data for those analyses that required baseline data. The number included in the FAS may vary across endpoints due to the degree of missing data for each endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Week 1 (N=508, 252) | -17.7 minutes |
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Week 2 (N=495, 248) | -15.7 minutes |
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Week 3 (N=488, 241) | -18.7 minutes |
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Month 1 Average (N=517, 254) | -18.0 minutes |
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Week 4 (N=473, 238) | -19.9 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Week 3 (N=488, 241) | -10.0 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Week 1 (N=508, 252) | -6.8 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Week 4 (N=473, 238) | -9.4 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Week 2 (N=495, 248) | -7.5 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase | Change From BL at Month 1 Average (N=517, 254) | -8.4 minutes |
Comparison: A Longitudinal Data Analysis Model was used to test the difference in LS mean change from baseline in sTSOm for Month 1 (Average of Weeks 1, 2, 3, 4) in the Suvorexant group vs. the Placebo group.p-value: 0.000295% CI: [-14.6, -4.5]Longitudinal Data Analysis
Secondary
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
Population: Full Analysis Set (FAS)-Efficacy; all randomized participants who had ≥1 post-randomization observation for the analysis endpoint subsequent to ≥1 dose of study treatment, and baseline data for those analyses that required baseline data. The number included in the FAS may vary across endpoints due to the degree of missing data for each endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Week 1 (N=508, 252) | 41.1 minutes |
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Week 2 (N=495, 248) | 32.4 minutes |
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Week 3 (N=488, 241) | 39.6 minutes |
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Month 1 Average (N=517, 254) | 38.7 minutes |
| Suvorexant | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Week 4 (N=473, 238) | 41.6 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Week 3 (N=488, 241) | 16.4 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Week 1 (N=508, 252) | 14.1 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Week 4 (N=473, 238) | 18.7 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Week 2 (N=495, 248) | 14.7 minutes |
| Placebo | Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase | Change From BL at Month 1 Average (N=517, 254) | 16.0 minutes |
Comparison: A Longitudinal Data Analysis Model was used to test the difference in LS mean change from baseline in sTSTm for Month 1 (Average of Weeks 1, 2, 3, 4) in the Suvorexant group vs. the Placebo group.p-value: <0.000195% CI: [16.4, 29]Longitudinal Data Analysis
Secondary
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)
Population: Participants in the APaT population who completed the entire DB Treatment Phase, had a baseline measurement, had taken at least one dose of DB Run-out study medication, and had a measurement on at least one of the nights of the DB Run-out Phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Suvorexant | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Nights 1, 2 or 3 (n=152, 157, 152) | 28.9 percentage of participants |
| Suvorexant | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Night 3 (n=131, 146, 139) | 16.8 percentage of participants |
| Suvorexant | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Night 2 (n=138, 146, 145) | 19.6 percentage of participants |
| Suvorexant | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Night 1 (n=137, 142, 139) | 17.5 percentage of participants |
| Placebo | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Night 3 (n=131, 146, 139) | 37.7 percentage of participants |
| Placebo | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Night 2 (n=138, 146, 145) | 35.6 percentage of participants |
| Placebo | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Night 1 (n=137, 142, 139) | 33.8 percentage of participants |
| Placebo | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Nights 1, 2 or 3 (n=152, 157, 152) | 51.0 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Night 2 (n=138, 146, 145) | 26.9 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Night 1 (n=137, 142, 139) | 28.8 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Nights 1, 2 or 3 (n=152, 157, 152) | 40.1 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase | Rebound on Night 3 (n=131, 146, 139) | 31.7 percentage of participants |
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with sTST rebound effects during Night 1 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Placebo (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.36595% CI: [-5.8, 15.8]Miettinen & Nurminen Method
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with sTST rebound effects during Night 2 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Placebo (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.10995% CI: [-2, 19.2]Miettinen & Nurminen Method
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with sTST rebound effects during Night 3 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Placebo (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.28795% CI: [-5.1, 16.9]Miettinen & Nurminen Method
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with sTST rebound effects during Nights 1, 2, or 3 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Placebo (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.05795% CI: [-0.3, 21.7]Miettinen & Nurminen Method
Secondary
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).
Time frame: Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13)
Population: Participants in the APaT population who completed the entire DB Treatment Phase, had a baseline measurement, had taken at least one dose of DB Run-out study medication, and had a measurement on at least one of the nights of the DB Run-out Phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Suvorexant | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Nights 1, 2 or 3 (n=152, 157, 152) | 31.6 percentage of participants |
| Suvorexant | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Night 2 (n=138, 146, 145) | 18.8 percentage of participants |
| Suvorexant | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Night 1 (n=137, 142, 139) | 16.8 percentage of participants |
| Suvorexant | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Night 3 (n=131, 146, 139) | 19.1 percentage of participants |
| Placebo | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Nights 1, 2 or 3 (n=152, 157, 152) | 40.8 percentage of participants |
| Placebo | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Night 3 (n=131, 146, 139) | 30.1 percentage of participants |
| Placebo | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Night 2 (n=138, 146, 145) | 30.1 percentage of participants |
| Placebo | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Night 1 (n=137, 142, 139) | 26.8 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Night 2 (n=138, 146, 145) | 24.8 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Night 1 (n=137, 142, 139) | 22.3 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Night 3 (n=131, 146, 139) | 25.2 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase | Rebound on Nights 1, 2 or 3 (n=152, 157, 152) | 36.2 percentage of participants |
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with sTSO rebound effects during Night 1 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Placebo (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.38695% CI: [-5.7, 14.5]Miettinen & Nurminen Method
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with sTSO rebound effects during Night 2 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Placebo (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.31195% CI: [-5, 15.5]Miettinen & Nurminen Method
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with sTSO rebound effects during Night 3 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Placebo (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.35195% CI: [-5.5, 15.3]Miettinen & Nurminen Method
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with sTSO rebound effects during Nights 1, 2, or 3 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Placebo (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.40995% CI: [-6.3, 15.3]Miettinen & Nurminen Method
Secondary
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])
Population: Participants in the APaT population who completed the entire DB Treatment Phase, had at least one measurement at the end of the DB Treatment Phase (Month 12), had taken at least one dose of Run-out study medication, and had a measurement on at least one of the nights of the DB Run-out Phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Suvorexant | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Withdrawal Symptoms on Night 3 (n=116, 120, 128) | 1.7 percentage of participants |
| Suvorexant | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Withdrawal Symptoms on Night 1 (n=121, 122, 131) | 0.8 percentage of participants |
| Suvorexant | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Symptoms Across Nights 1, 2, & 3 (n=129, 129, 136) | 6.2 percentage of participants |
| Suvorexant | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Withdrawal Symptoms on Night 2 (n=121, 124, 125) | 0.8 percentage of participants |
| Placebo | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Withdrawal Symptoms on Night 3 (n=116, 120, 128) | 2.5 percentage of participants |
| Placebo | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Withdrawal Symptoms on Night 2 (n=121, 124, 125) | 3.2 percentage of participants |
| Placebo | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Withdrawal Symptoms on Night 1 (n=121, 122, 131) | 1.6 percentage of participants |
| Placebo | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Symptoms Across Nights 1, 2, & 3 (n=129, 129, 136) | 6.2 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Withdrawal Symptoms on Night 2 (n=121, 124, 125) | 2.4 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Withdrawal Symptoms on Night 1 (n=121, 122, 131) | 1.5 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Symptoms Across Nights 1, 2, & 3 (n=129, 129, 136) | 5.1 percentage of participants |
| Placebo (DB Treatment)/Placebo (DB Discontinuation) | Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ) | Withdrawal Symptoms on Night 3 (n=116, 120, 128) | 0.8 percentage of participants |
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with withdrawal symptoms during Night 1 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Suvorexant (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.56795% CI: [-5.1, 3.1]Miettinen & Nurminen Method
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with withdrawal symptoms during Night 2 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Suvorexant (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.18595% CI: [-7.3, 1.6]Miettinen & Nurminen Method
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with withdrawal symptoms during Night 3 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Suvorexant (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 0.6895% CI: [-5.6, 3.9]Miettinen & Nurminen Method
Comparison: The method of Miettinen and Nurminen was used to calculate the p-value and compute the confidence interval for the point difference in a pairwise comparison of the percentage of participants with withdrawal symptoms across Nights 1, 2, and 3 in the Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) group vs. the Suvorexant (DB Treatment)/Placebo (DB Discontinuation) group.p-value: 195% CI: [-6.4, 6.4]Miettinen & Nurminen Method
Other Pre-specified
Number of Participants Who Reported Suicidal Ideation and/or Behavior On Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS)
Suicidal ideation and/or behavior that occurred on study was also assessed using the C-SSRS, a rater-administered questionnaire used to prospectively assess suicidal ideation and suicidal behavior. C-SSRS assessment was based upon a clinician's interpretation of the participant's responses to the C-SSRS questions, not by a numbered scale. Suicidal ideation and/or behaviors identified on the C-SSRS may not have been considered an adverse event, based on the investigator's judgment.
Time frame: From the first day of study treatment through study follow-up (up to 14 months)
Population: All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suvorexant | Number of Participants Who Reported Suicidal Ideation and/or Behavior On Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS) | 6 participants |
| Placebo | Number of Participants Who Reported Suicidal Ideation and/or Behavior On Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS) | 0 participants |