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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.

Tracking Information
First Submitted Date  ICMJE November 25, 2009
First Posted Date  ICMJE November 30, 2009
Results First Submitted Date  ICMJE August 19, 2014
Results First Posted Date  ICMJE August 29, 2014
Last Update Posted Date September 21, 2018
Actual Study Start Date  ICMJE December 10, 2009
Actual Primary Completion Date May 17, 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 19, 2014)
  • 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 ]
    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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From the first day of study treatment up to 12 months ]
    Perceptual distortions associated with transitions between wakefulness and sleep were termed as hypnagogic (occurring during the onset of sleep) or hypnopompic (occurring during onset of wakefulness) hallucinations.
  • Percentage of Participants Who Experienced 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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 25, 2009)
  • Proportion of patients who experience narcolepsy-like events, including cataplexy [ Time Frame: 12 months ]
  • Proportion of patients who experience complex sleep-related behavior [ Time Frame: 12 months ]
  • Proportion of patients who experience falls [ Time Frame: 12 months ]
  • Proportion of patients who experience suicidal ideation and/or behaviors [ Time Frame: 12 months ]
Change History Complete list of historical versions of study NCT01021813 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 3, 2014)
  • 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]) ]
    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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2009)
  • Mean change from baseline in subjective total sleep time (sTST) after 1st month of treatment [ Time Frame: Weeks 1, 2, 3, and 4 ]
  • Mean change from baseline in subjective time to sleep onset (sTSO) after the first month of treatment [ Time Frame: Weeks 1, 2, 3, and 4 ]
Current Other Pre-specified Outcome Measures
 (submitted: August 19, 2014)
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) ]
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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Long Term Safety Study of Suvorexant in Participants With Primary Insomnia (MK-4305-009 AM3)
Official Title  ICMJE A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Long Term Safety Study of MK-4305 in Patients With Primary Insomnia
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Insomnia
Intervention  ICMJE
  • Drug: Suvorexant
    Oral tablet (30 mg and 10 mg), administered daily before bedtime
    Other Name: MK-4305
  • Drug: Dose-matched Placebo to Suvorexant
    Oral tablet, administered daily before bedtime
Study Arms  ICMJE
  • Experimental: Suvorexant
    After a 1-week single-blind placebo run-in, participants received suvorexant (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime for 12 months during the Treatment Phase.
    Interventions:
    • Drug: Suvorexant
    • Drug: Dose-matched Placebo to Suvorexant
  • Placebo Comparator: Placebo
    After a 1-week single-blind placebo run-in, participants received dose-matched placebo to suvorexant (administered according to age) daily before bedtime for 12 months during the Treatment Phase.
    Intervention: Drug: Dose-matched Placebo to Suvorexant
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 19, 2014)
781
Original Estimated Enrollment  ICMJE
 (submitted: November 25, 2009)
750
Actual Study Completion Date  ICMJE August 1, 2011
Actual Primary Completion Date May 17, 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Belgium,   Canada,   Colombia,   Denmark,   Finland,   France,   Germany,   Hungary,   South Africa,   Spain,   Sweden,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT01021813
Other Study ID Numbers  ICMJE 4305-009
2009_696 ( Other Identifier: Merck Registration Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Merck Sharp & Dohme Corp.
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP