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

NCT01021813 | Completed Phase 3 Results DMC

• 2 other identifiers: 4305-0092009_696
• Study Type: interventional
• Target: 781
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Insomnia

Outcome Measures

Primary Outcomes (7)

• Percentage of Participants Who Experienced Cataplexy Adverse Events (AEs) During the Double-Blind (DB) Treatment Phase

  Cataplexy is defined as a sudden loss of muscle tone while awake which prevents voluntary movement.

  From the first day of study treatment up to 12 months

• Percentage of Participants Who Experienced Sleep Paralysis AEs During the DB Treatment Phase

  Sleep paralysis was defined as the inability to perform voluntary muscle movements during sleep. Sleep paralysis adverse events included sleep-onset paralysis (paralysis as one is falling asleep).

  From the first day of study treatment up to 12 months

• Percentage of Participants Who Experienced Complex Sleep-related Behaviors AEs During the DB Treatment Phase

  Complex sleep-related behaviors were reported as ECIs and were characterized by patients engaging in specific activities while asleep (e.g., eating, drinking, preparing meals, making phone calls, having sex, driving, and sleep walking).

  From the first day of study treatment up to 12 months

• Percentage of Participants Who Experienced Falls AEs During the DB Treatment Phase

  Falls were adjudicated (to establish whether a fall event was due to cataplexy).

  From the first day of study treatment up to 12 months

• Percentage of Participants Who Experienced Suicidal Ideation and/or Behavior AEs During the DB Treatment Phase

  Suicidal ideation included suicidal plans, suicidal tendency, death wishes, life weariness, and suicidal intention. Suicidal behaviors included suicide attempts, suicide gesture, and self-injurious behaviour. Suicidal ideation and/or behavior was reported as an AE and considered an ECI.

  From the first day of study treatment up to 12 months

• Percentage of Participants Who Experienced Hypnagogic/Hypnopompic Hallucinations AEs During the DB Treatment Phase

  Perceptual distortions associated with transitions between wakefulness and sleep were termed as hypnagogic (occurring during the onset of sleep) or hypnopompic (occurring during onset of wakefulness) hallucinations.

  From the first day of study treatment up to 12 months

• Percentage of Participants Who Experienced Selected AEs Associated With Potential for Abuse During the DB Treatment Phase

  The pre-specified terms which were suggestive of abuse potential on this study included depersonalization (feeling of watching oneself act, while having no control over a situation), derealization (alteration in the perception or experience of the external world so that it seems unreal), dissociation (includes a wide array of experiences from mild detachment from immediate surroundings to more severe detachment from physical and emotional experience), euphoric mood (exaggerated feeling of physical and emotional well-being and optimism not consonant with apparent stimuli or events), mania (state of abnormally elevated or irritable mood, arousal, and/or energy levels), hallucination (perception in the absence of a stimulus which has qualities of real perception), and potential study medication misuse.

  From the first day of study treatment up to 12 months

Secondary Outcomes (5)

• Percentage of Participants With Withdrawal Symptoms During the DB Run-Out Phase: Tyrer Withdrawal Symptom Questionnaire (WSQ)

  Evening of Month 12 visit and next 3 consecutive days (Night 1, 2, and 3 of Discontinuation Phase [otherwise known as the Run-out])

• Percentage of Participants With Rebound As Defined By Decreased Subjective Total Sleep Time (sTST) During the DB Run-Out Phase

  Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13)

• Percentage of Participants With Rebound As Defined By Increased Subjective Time to Sleep Onset (sTSO) During the DB Run-Out Phase

  Baseline (Month 1) and first 3 days of Randomized Discontinuation Phase (otherwise known as the Run-out, Month 13)

• Least Squares (LS) Mean Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) During First Month of Treatment Phase

  Baseline, Week 1, Week 2, Week 3, and Week 4

• Least Squares (LS) Mean Change From Baseline in Mean Subjective Time To Sleep Onset (sTSOm) During First Month of Treatment Phase

  Baseline, Week 1, Week 2, Week 3, and Week 4

Other Outcomes (1)

• Number of Participants Who Reported Suicidal Ideation and/or Behavior On Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS)

  From the first day of study treatment through study follow-up (up to 14 months)

Study Arms (2)

Suvorexant

EXPERIMENTAL

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.

Drug: Suvorexant; Drug: Dose-matched Placebo to Suvorexant

Placebo

PLACEBO COMPARATOR

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.

Drug: Dose-matched Placebo to Suvorexant

Interventions

Suvorexant DRUG

Oral tablet (30 mg and 10 mg), administered daily before bedtime

Also known as: MK-4305

Suvorexant

Dose-matched Placebo to Suvorexant DRUG

Oral tablet, administered daily before bedtime

Placebo; Suvorexant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (3)

• 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.

  PMID: 28427826 DERIVED

• 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.

  PMID: 28265715 DERIVED

• 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.

  PMID: 24680372 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Results Point of Contact

• Title: Vice President, Late Stage Development Group Leader
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2009
• First Posted: November 30, 2009
• Study Start: December 10, 2009
• Primary Completion: May 17, 2011
• Study Completion: August 1, 2011
• Last Updated: September 21, 2018
• Results First Posted: August 29, 2014

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share