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A Long Term Safety Study of Suvorexant in Participants With Primary Insomnia (MK-4305-009 AM3)

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ClinicalTrials.gov Identifier: NCT01021813
Recruitment Status : Completed
First Posted : November 30, 2009
Results First Posted : August 29, 2014
Last Update Posted : September 21, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Insomnia
Interventions Drug: Suvorexant
Drug: Dose-matched Placebo to Suvorexant
Enrollment 781
Recruitment Details  
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.
Arm/Group Title Suvorexant Placebo Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) Suvorexant (DB Treatment)/Placebo (DB Discontinuation) Placebo (DB Treatment)/Placebo (DB Discontinuation)
Hide Arm/Group Description 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. 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. Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received their same dose of suvorexant during a 2-month DB Randomized Discontinuation Phase. Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase. Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Phase, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase.
Period Title: DB Treatment Phase
Started 522 259 0 0 0
Treated 521 258 0 0 0
Completed 322 162 0 0 0
Not Completed 200 97 0 0 0
Reason Not Completed
Adverse Event             60             22             0             0             0
Lack of Efficacy             44             28             0             0             0
Lost to Follow-up             14             12             0             0             0
Physician Decision             17             8             0             0             0
Pregnancy             1             0             0             0             0
Protocol Violation             4             3             0             0             0
Withdrawal by Subject             60             24             0             0             0
Period Title: DB Randomized Discontinuation Phase
Started 0 0 156 166 162
Completed 0 0 152 161 157
Not Completed 0 0 4 5 5
Reason Not Completed
Adverse Event             0             0             0             3             1
Lack of Efficacy             0             0             0             1             0
Lost to Follow-up             0             0             0             0             1
Protocol Violation             0             0             1             0             0
Withdrawal by Subject             0             0             3             1             3
Arm/Group Title Suvorexant Placebo Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 521 258 779
Hide Baseline Analysis Population Description
781 participants were randomized on study (suvorexant=522, placebo=259). 2 participants were randomized but not treated, thus the total number of participants evaluated for baseline age and gender was 779 (suvorexant=521, placebo=258). 771 participants had data available for evaluation of baseline sleep parameters (suvorexant=517, placebo=254)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 521 participants 258 participants 779 participants
61.3  (14.5) 62.0  (14.6) 61.5  (14.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 521 participants 258 participants 779 participants
Female
287
  55.1%
149
  57.8%
436
  56.0%
Male
234
  44.9%
109
  42.2%
343
  44.0%
Mean Subjective Total Sleep Time (sTSTm)   [1] 
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 521 participants 258 participants 779 participants
320.4  (76.1) 329.9  (79.4) 323.5  (77.3)
[1]
Measure Description:

The baseline sTSTm was defined as the participant’s reported total amount of time spent asleep before waking for the day (measured in minutes), calculated as the mean of the last 7 (non-missing) daily e-diary values obtained during the placebo run-in phase.

(n=517, n=254)

Mean Subjective Time to Sleep Onset in minutes (sTSOm)   [1] 
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 521 participants 258 participants 779 participants
65.9  (63.8) 65.0  (60.6) 65.6  (62.7)
[1]
Measure Description:

The baseline sTSOm was defined as the participant’s reported time that he or she required to fall asleep (measured in minutes), calculated as the mean of the last 7 (non-missing) daily e-diary values obtained during the placebo run-in phase.

(n=517, n=254)

1.Primary Outcome
Title Percentage of Participants Who Experienced Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Arm/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 521 258
Measure Type: Number
Unit of Measure: percentage of participants
0.0 0.0
2.Primary Outcome
Title Percentage of Participants Who Experienced Sleep Paralysis AEs During the DB Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment
Arm/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 521 258
Measure Type: Number
Unit of Measure: percentage of participants
0.4 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant, Placebo
Comments 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 .
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Miettinen & Nurminen Method.
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.1 to 1.4
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Arm/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 521 258
Measure Type: Number
Unit of Measure: percentage of participants
any complex sleep-related behaviors 0.2 0.0
somnambulism 0.2 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.482
Comments [Not Specified]
Method Miettinen & Nurminen Method.
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-1.3 to 1.1
Estimation Comments [Not Specified]
4.Primary Outcome
Title Percentage of Participants Who Experienced Falls AEs During the DB Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Arm/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 521 258
Measure Type: Number
Unit of Measure: percentage of participants
2.3 3.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.508
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-3.9 to 1.5
Estimation Comments [Not Specified]
5.Primary Outcome
Title Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Arm/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 521 258
Measure Type: Number
Unit of Measure: percentage of participants
0.8 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.159
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage of AEs
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.7 to 2.0
Estimation Comments [Not Specified]
6.Primary Outcome
Title Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Arm/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 521 258
Measure Type: Number
Unit of Measure: percentage of participants
Any hypnagogic/hypnopompic hallucinations AEs 0.8 0.0
Hypnagogic hallucination 0.6 0.0
Hypnopompic hallucination 0.2 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.159
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.7 to 2.0
Estimation Comments [Not Specified]
7.Primary Outcome
Title Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Arm/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 521 258
Measure Type: Number
Unit of Measure: percentage of participants
any selected AE of potential abuse 3.5 3.9
Drug maladministration 2.3 3.9
Derealisation 0.2 0.0
Hallucination, auditory 0.2 0.0
Hallucination, visual 0.2 0.0
Hypnagogic hallucination 0.6 0.0
Hypnopompic hallucination 0.2 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.767
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-3.8 to 2.2
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)
Hide Description

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])
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) Suvorexant (DB Treatment)/Placebo (DB Discontinuation) Placebo (DB Treatment)/Placebo (DB Discontinuation)
Hide Arm/Group Description:
Following treatment with suvorexant during the 12-Month DB Treatment Period, participants received their same dose of suvorexant during a 2-month DB Discontinuation Period.
Following treatment with suvorexant during the 12-Month DB Treatment Period, participants received dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
Overall Number of Participants Analyzed 129 129 136
Measure Type: Number
Unit of Measure: percentage of participants
Withdrawal Symptoms on Night 1 (n=121, 122, 131) 0.8 1.6 1.5
Withdrawal Symptoms on Night 2 (n=121, 124, 125) 0.8 3.2 2.4
Withdrawal Symptoms on Night 3 (n=116, 120, 128) 1.7 2.5 0.8
Symptoms Across Nights 1, 2, & 3 (n=129, 129, 136) 6.2 6.2 5.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Suvorexant (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.567
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Night 1
Estimated Value -0.81
Confidence Interval (2-Sided) 95%
-5.1 to 3.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Suvorexant (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.185
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Night 2
Estimated Value -2.40
Confidence Interval (2-Sided) 95%
-7.3 to 1.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Suvorexant (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.680
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Night 3
Estimated Value -0.78
Confidence Interval (2-Sided) 95%
-5.6 to 3.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Suvorexant (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Across Nights
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-6.4 to 6.4
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) Suvorexant (DB Treatment)/Placebo (DB Discontinuation) Placebo (DB Treatment)/Placebo (DB Discontinuation)
Hide Arm/Group Description:
Following treatment with suvorexant during the 12-Month DB Treatment Period, participants received their same dose of suvorexant during a 2-month DB Discontinuation Period.
Following treatment with suvorexant during the 12-Month DB Treatment Period, participants received dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
Overall Number of Participants Analyzed 152 157 152
Measure Type: Number
Unit of Measure: percentage of participants
Rebound on Night 1 (n=137, 142, 139) 17.5 33.8 28.8
Rebound on Night 2 (n=138, 146, 145) 19.6 35.6 26.9
Rebound on Night 3 (n=131, 146, 139) 16.8 37.7 31.7
Rebound on Nights 1, 2 or 3 (n=152, 157, 152) 28.9 51.0 40.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Placebo (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.365
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Night 1
Estimated Value 5.03
Confidence Interval (2-Sided) 95%
-5.8 to 15.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Placebo (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Night 2
Estimated Value 8.72
Confidence Interval (2-Sided) 95%
-2.0 to 19.2
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Placebo (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.287
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Night 3
Estimated Value 6.02
Confidence Interval (2-Sided) 95%
-5.1 to 16.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Placebo (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.057
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage:Night 1, 2 or 3
Estimated Value 10.82
Confidence Interval (2-Sided) 95%
-0.3 to 21.7
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) Suvorexant (DB Treatment)/Placebo (DB Discontinuation) Placebo (DB Treatment)/Placebo (DB Discontinuation)
Hide Arm/Group Description:
Following treatment with suvorexant during the 12-Month DB Treatment Period, participants received their same dose of suvorexant during a 2-month DB Discontinuation Period.
Following treatment with suvorexant during the 12-Month DB Treatment Period, participants received dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Period, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Discontinuation Period.
Overall Number of Participants Analyzed 152 157 152
Measure Type: Number
Unit of Measure: percentage of participants
Rebound on Night 1 (n=137, 142, 139) 16.8 26.8 22.3
Rebound on Night 2 (n=138, 146, 145) 18.8 30.1 24.8
Rebound on Night 3 (n=131, 146, 139) 19.1 30.1 25.2
Rebound on Nights 1, 2 or 3 (n=152, 157, 152) 31.6 40.8 36.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Placebo (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.386
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Night 1
Estimated Value 4.46
Confidence Interval (2-Sided) 95%
-5.7 to 14.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Placebo (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.311
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Night 2
Estimated Value 5.31
Confidence Interval (2-Sided) 95%
-5.0 to 15.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Placebo (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.351
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage: Night 3
Estimated Value 4.96
Confidence Interval (2-Sided) 95%
-5.5 to 15.3
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation), Placebo (DB Treatment)/Placebo (DB Discontinuation)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.409
Comments [Not Specified]
Method Miettinen & Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage:Night 1, 2 or 3
Estimated Value 4.58
Confidence Interval (2-Sided) 95%
-6.3 to 15.3
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 517 254
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
Change From BL at Week 1 (N=508, 252)
41.1
(36.9 to 45.3)
14.1
(8.2 to 20.1)
Change From BL at Week 2 (N=495, 248)
32.4
(28.1 to 36.7)
14.7
(8.6 to 20.8)
Change From BL at Week 3 (N=488, 241)
39.6
(35.3 to 44.0)
16.4
(10.3 to 22.6)
Change From BL at Week 4 (N=473, 238)
41.6
(37.1 to 46.1)
18.7
(12.3 to 25.1)
Change From BL at Month 1 Average (N=517, 254)
38.7
(35.0 to 42.3)
16.0
(10.8 to 21.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To account for multiplicity, Hochberg’s procedure was used to control the overall Type I error rate at the 5% level.
Method Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means: Month 1
Estimated Value 22.7
Confidence Interval (2-Sided) 95%
16.4 to 29.0
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 517 254
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
Change From BL at Week 1 (N=508, 252)
-17.7
(-20.9 to -14.5)
-6.8
(-11.4 to -2.3)
Change From BL at Week 2 (N=495, 248)
-15.7
(-19.2 to -12.2)
-7.5
(-12.4 to -2.6)
Change From BL at Week 3 (N=488, 241)
-18.7
(-22.2 to -15.2)
-10.0
(-14.9 to -5.0)
Change From BL at Week 4 (N=473, 238)
-19.9
(-23.1 to -16.6)
-9.4
(-14.1 to -4.8)
Change From BL at Month 1 Average (N=517, 254)
-18.0
(-20.9 to -15.1)
-8.4
(-12.5 to -4.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments To account for multiplicity, Hochberg’s procedure was used to control the overall Type I error rate at the 5% level.
Method Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means: Month 1
Estimated Value -9.5
Confidence Interval (2-Sided) 95%
-14.6 to -4.5
Estimation Comments [Not Specified]
13.Other Pre-specified Outcome
Title Number of Participants Who Reported Suicidal Ideation and/or Behavior On Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population; all randomized participants who received at least one dose of study treatment.
Arm/Group Title Suvorexant Placebo
Hide Arm/Group Description:
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. Following the Treatment Phase, these participants were randomized (at baseline) to suvorexant or placebo during the 2-month Randomized Discontinuation Phase.
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. Following the Treatment Phase, these participants continued on placebo during the 2-month Randomized Discontinuation Phase.
Overall Number of Participants Analyzed 521 258
Measure Type: Number
Unit of Measure: participants
6 0
Time Frame AEs were monitored from the time of the Prestudy Visit (~Study Day -14) up to the completion of the Follow-up call, occurring 14 days after Randomized Discontinuation Phase (~Study Day 420) or after the last dose of medication, whichever point was later.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Suvorexant Placebo Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) Suvorexant (DB Treatment)/Placebo (DB Discontinuation) Placebo (DB Treatment)/Placebo (DB Discontinuation) Suvorexant (DB Treatment)/Suvorexant (DB Run-out)/Follow-up Suvorexant (DB Treatment)/Placebo (DB Run-out)/Follow-up Placebo (DB Treatment)/Placebo (DB Run-out)/Follow-up
Hide Arm/Group Description 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. 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. Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received their same dose of suvorexant during a 2-month DB Randomized Discontinuation Phase. Following treatment with suvorexant during the 12-Month DB Treatment Phase, participants received dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase. Following treatment with dose-matched placebo to suvorexant during the 12-Month DB Treatment Phase, participants continued to receive dose-matched placebo to suvorexant during a 2-month DB Randomized Discontinuation Phase. Following treatment with suvorexant during both the 12-Month DB Treatment Period and the DB Run-out period, participants entered a Follow-up Phase which concluded with a follow-up phone call 14 days after the last dose of study medication (or 14 days after the Discontinuation visit, whichever time point was later) to report AEs. Following treatment with suvorexant during the 12-Month DB Treatment Period and treatment with dose-matched placebo during the DB the Run-out period, participants entered a Follow-up Phase which concluded with a follow-up phone call 14 days after the last dose of study medication (or 14 days after the Discontinuation visit, whichever time point was later) to report AEs. Following treatment with dose-matched placebo during both the 12-Month DB Treatment Period and the DB Run-out period, participants entered a Follow-up Phase which concluded with a follow-up phone call 14 days after the last dose of study medication (or 14 days after the Discontinuation visit, whichever time point was later) to report AEs.
All-Cause Mortality
Suvorexant Placebo Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) Suvorexant (DB Treatment)/Placebo (DB Discontinuation) Placebo (DB Treatment)/Placebo (DB Discontinuation) Suvorexant (DB Treatment)/Suvorexant (DB Run-out)/Follow-up Suvorexant (DB Treatment)/Placebo (DB Run-out)/Follow-up Placebo (DB Treatment)/Placebo (DB Run-out)/Follow-up
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Suvorexant Placebo Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) Suvorexant (DB Treatment)/Placebo (DB Discontinuation) Placebo (DB Treatment)/Placebo (DB Discontinuation) Suvorexant (DB Treatment)/Suvorexant (DB Run-out)/Follow-up Suvorexant (DB Treatment)/Placebo (DB Run-out)/Follow-up Placebo (DB Treatment)/Placebo (DB Run-out)/Follow-up
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/521 (5.18%)      17/258 (6.59%)      3/156 (1.92%)      1/166 (0.60%)      1/162 (0.62%)      1/260 (0.38%)      0/261 (0.00%)      2/258 (0.78%)    
Cardiac disorders                 
Atrial fibrillation  1/521 (0.19%)  1 3/258 (1.16%)  3 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Coronary artery disease  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Ear and labyrinth disorders                 
Vertigo positional  1/521 (0.19%)  1 0/258 (0.00%)  0 1/156 (0.64%)  1 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Gastrointestinal disorders                 
Gastrooesophageal reflux  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Ileus  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Pancreatitis  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
General disorders                 
Non-cardiac chest pain  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Infections and infestations                 
Abdominal infection  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Cellulitis  0/521 (0.00%)  0 0/258 (0.00%)  0 1/156 (0.64%)  1 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Diverticulitis  2/521 (0.38%)  2 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Erysipelas  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Pneumonia  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Postoperative wound infection  0/521 (0.00%)  0 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 1/258 (0.39%)  1
Urinary tract infection  1/521 (0.19%)  1 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Injury, poisoning and procedural complications                 
Clavicle fracture  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Concussion  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Joint dislocation  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Tendon rupture  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Musculoskeletal and connective tissue disorders                 
Arthralgia  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Back pain  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Meniscal degeneration  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Spinal column stenosis  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Spondylitis  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
B-cell lymphoma  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Basal cell carcinoma  2/521 (0.38%)  2 2/258 (0.78%)  2 0/156 (0.00%)  0 0/166 (0.00%)  0 1/162 (0.62%)  1 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Breast cancer in situ  0/521 (0.00%)  0 0/258 (0.00%)  0 0/156 (0.00%)  0 1/166 (0.60%)  1 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Hodgkin's disease  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Malignant melanoma  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Neoplasm skin  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Squamous cell carcinoma  1/521 (0.19%)  1 1/258 (0.39%)  1 1/156 (0.64%)  1 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Uterine cancer  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Nervous system disorders                 
Cerebral infarction  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Cervicobrachial syndrome  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Headache  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Migraine  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Transient ischaemic attack  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Pregnancy, puerperium and perinatal conditions                 
Abortion spontaneous  0/521 (0.00%)  0 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 1/260 (0.38%)  1 0/261 (0.00%)  0 0/258 (0.00%)  0
Psychiatric disorders                 
Suicidal ideation  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Renal and urinary disorders                 
Calculus ureteric  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Renal failure acute  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Reproductive system and breast disorders                 
Vaginal prolapse  0/521 (0.00%)  0 1/258 (0.39%)  1 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                 
Lung disorder  1/521 (0.19%)  1 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Vascular disorders                 
Hypertension  0/521 (0.00%)  0 0/258 (0.00%)  0 0/156 (0.00%)  0 0/166 (0.00%)  0 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 1/258 (0.39%)  1
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Suvorexant Placebo Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) Suvorexant (DB Treatment)/Placebo (DB Discontinuation) Placebo (DB Treatment)/Placebo (DB Discontinuation) Suvorexant (DB Treatment)/Suvorexant (DB Run-out)/Follow-up Suvorexant (DB Treatment)/Placebo (DB Run-out)/Follow-up Placebo (DB Treatment)/Placebo (DB Run-out)/Follow-up
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   184/521 (35.32%)      63/258 (24.42%)      7/156 (4.49%)      5/166 (3.01%)      9/162 (5.56%)      2/260 (0.77%)      1/261 (0.38%)      2/258 (0.78%)    
General disorders                 
Fatigue  34/521 (6.53%)  40 5/258 (1.94%)  5 0/156 (0.00%)  0 0/166 (0.00%)  0 1/162 (0.62%)  1 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Infections and infestations                 
Nasopharyngitis  42/521 (8.06%)  53 20/258 (7.75%)  25 5/156 (3.21%)  5 2/166 (1.20%)  2 4/162 (2.47%)  4 2/260 (0.77%)  2 0/261 (0.00%)  0 1/258 (0.39%)  1
Upper respiratory tract infection  28/521 (5.37%)  32 11/258 (4.26%)  13 1/156 (0.64%)  1 2/166 (1.20%)  3 1/162 (0.62%)  1 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Nervous system disorders                 
Dizziness  24/521 (4.61%)  29 16/258 (6.20%)  19 0/156 (0.00%)  0 0/166 (0.00%)  0 1/162 (0.62%)  1 0/260 (0.00%)  0 0/261 (0.00%)  0 0/258 (0.00%)  0
Headache  43/521 (8.25%)  66 22/258 (8.53%)  25 2/156 (1.28%)  2 0/166 (0.00%)  0 2/162 (1.23%)  2 0/260 (0.00%)  0 1/261 (0.38%)  1 0/258 (0.00%)  0
Somnolence  69/521 (13.24%)  76 7/258 (2.71%)  7 0/156 (0.00%)  0 1/166 (0.60%)  1 0/162 (0.00%)  0 0/260 (0.00%)  0 0/261 (0.00%)  0 1/258 (0.39%)  1
1
Term from vocabulary, MedDRA 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01021813     History of Changes
Other Study ID Numbers: 4305-009
2009_696 ( Other Identifier: Merck Registration Number )
First Submitted: November 25, 2009
First Posted: November 30, 2009
Results First Submitted: August 19, 2014
Results First Posted: August 29, 2014
Last Update Posted: September 21, 2018