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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01021813
First received: November 25, 2009
Last updated: September 3, 2014
Last verified: September 2014
Results First Received: August 19, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Insomnia
Interventions: Drug: Suvorexant
Drug: Dose-matched Placebo to Suvorexant

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.
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.
Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation) 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.
Suvorexant (DB Treatment)/Placebo (DB Discontinuation) 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.
Placebo (DB Treatment)/Placebo (DB Discontinuation) 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.

Participant Flow for 2 periods

Period 1:   DB Treatment Phase
    Suvorexant     Placebo     Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation)     Suvorexant (DB Treatment)/Placebo (DB Discontinuation)     Placebo (DB Treatment)/Placebo (DB Discontinuation)  
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  
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 2:   DB Randomized Discontinuation Phase
    Suvorexant     Placebo     Suvorexant (DB Treatment)/Suvorexant (DB Discontinuation)     Suvorexant (DB Treatment)/Placebo (DB Discontinuation)     Placebo (DB Treatment)/Placebo (DB Discontinuation)  
STARTED     0     0     156     166     162  
COMPLETED     0     0     152     161     157  
NOT COMPLETED     0     0     4     5     5  
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  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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)

Reporting Groups
  Description
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.
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.
Total Total of all reporting groups

Baseline Measures
    Suvorexant     Placebo     Total  
Number of Participants  
[units: participants]
  521     258     779  
Age  
[units: years]
Mean ± Standard Deviation
  61.3  ± 14.5     62.0  ± 14.6     61.5  ± 14.5  
Gender  
[units: participants]
     
Female     287     149     436  
Male     234     109     343  
Mean Subjective Total Sleep Time (sTSTm) [1]
[units: minutes]
Mean ± Standard Deviation
  320.4  ± 76.1     329.9  ± 79.4     323.5  ± 77.3  
Mean Subjective Time to Sleep Onset in minutes (sTSOm) [2]
[units: minutes]
Mean ± Standard Deviation
  65.9  ± 63.8     65.0  ± 60.6     65.6  ± 62.7  
[1]

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)

[2]

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)




  Outcome Measures
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1.  Primary:   Percentage of Participants Who Experienced Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase   [ Time Frame: From the first day of study treatment up to 12 months ]

2.  Primary:   Percentage of Participants Who Experienced Sleep Paralysis AEs During the DB Treatment Phase   [ Time Frame: From the first day of study treatment up to 12 months ]

3.  Primary:   Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase   [ Time Frame: From the first day of study treatment up to 12 months ]

4.  Primary:   Percentage of Participants Who Experienced Falls AEs During the DB Treatment Phase   [ Time Frame: From the first day of study treatment up to 12 months ]

5.  Primary:   Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase   [ Time Frame: From the first day of study treatment up to 12 months ]

6.  Primary:   Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase   [ Time Frame: From the first day of study treatment up to 12 months ]

7.  Primary:   Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase   [ Time Frame: From the first day of study treatment up to 12 months ]

8.  Secondary:   Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)   [ 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]) ]

9.  Secondary:   Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase   [ Time Frame: Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13) ]

10.  Secondary:   Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase   [ Time Frame: Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13) ]

11.  Secondary:   Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase   [ Time Frame: Baseline, Week 1, Week 2, Week 3, and Week 4 ]

12.  Secondary:   Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase   [ Time Frame: Baseline, Week 1, Week 2, Week 3, and Week 4 ]

13.  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)   [ Time Frame: From the first day of study treatment through study follow-up (up to 14 months) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


No publications provided by Merck Sharp & Dohme Corp.

Publications automatically indexed to this study:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01021813     History of Changes
Other Study ID Numbers: 4305-009, 2009_696
Study First Received: November 25, 2009
Results First Received: August 19, 2014
Last Updated: September 3, 2014
Health Authority: United States: Food and Drug Administration