Clinical trial NCT01021813: A Long Term Safety Study of Suvorexant in Participants With Primary Insomnia (MK-4305-009 AM3)
Official title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Long Term Safety Study of MK-4305 in Patients With Primary Insomnia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Insomnia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-11-30
Enrollment: 781
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Who Experienced Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase
timeFrame: From the first day of study treatment up to 12 months
measure: Percentage of Participants Who Experienced Sleep Paralysis AEs During the DB Treatment Phase
timeFrame: From the first day of study treatment up to 12 months
measure: Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase
timeFrame: From the first day of study treatment up to 12 months
measure: Percentage of Participants Who Experienced Falls AEs During the DB Treatment Phase
timeFrame: From the first day of study treatment up to 12 months
measure: Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase
timeFrame: From the first day of study treatment up to 12 months
measure: Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase
timeFrame: From the first day of study treatment up to 12 months
measure: Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase
timeFrame: From the first day of study treatment up to 12 months
Secondary outcomes:
measure: Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)
timeFrame: Evening of Month 12 visit and next 3 consecutive days (Night 1, 2, and 3 of Discontinuation Phase [otherwise known as the Run-out])
measure: Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase
timeFrame: Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13)
measure: Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase
timeFrame: Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13)
measure: Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase
timeFrame: Baseline, Week 1, Week 2, Week 3, and Week 4
measure: Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase
timeFrame: Baseline, Week 1, Week 2, Week 3, and Week 4
Other outcomes:
measure: Number of Participants Who Reported Suicidal Ideation and/or Behavior On Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: From the first day of study treatment through study follow-up (up to 14 months)
Locations:
Study officials:
References:
citation: Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Suvorexant in Elderly Patients with Insomnia: Pooled Analyses of Data from Phase III Randomized Controlled Clinical Trials. Am J Geriatr Psychiatry. 2017 Jul;25(7):791-802. doi: 10.1016/j.jagp.2017.03.004. Epub 2017 Mar 8.
citation: Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data. Psychopharmacology (Berl). 2017 Jun;234(11):1703-1711. doi: 10.1007/s00213-017-4573-1. Epub 2017 Mar 7.
citation: Michelson D, Snyder E, Paradis E, Chengan-Liu M, Snavely DB, Hutzelmann J, Walsh JK, Krystal AD, Benca RM, Cohn M, Lines C, Roth T, Herring WJ. Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014 May;13(5):461-71. doi: 10.1016/S1474-4422(14)70053-5. Epub 2014 Mar 27.