Phase IIB 2-Period Crossover Polysomnography Study in Participants With Primary Insomnia (MK-4305-006)

A Phase IIb, Multicenter, Randomized, Double-Blind Placebo-Controlled, 2-period Adaptive Crossover Polysomnography Study to Evaluate Safety and Efficacy of MK-4305 in Patients With Primary Insomnia

A cross-over, polysomnography study to test the safety, tolerability and effectiveness of different doses of suvorexant (MK-4305) in the treatment of patients with primary insomnia.

Study Overview

• Status: Completed
• Conditions: Primary Insomnia
• Intervention / Treatment: Drug: Suvorexant; Drug: Dose-matched Placebo to Suvorexant

• Study Type: Interventional
• Enrollment (Actual): 254
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has a diagnosis of Primary Insomnia based on sleep history and the investigator's judgment
• Must be willing to stay overnight at a sleep laboratory
• Must be willing to stay in bed for at least 8 hours each night while at the sleep laboratory
• Regular bedtime is between 9 PM and 12 AM (midnight)

Exclusion Criteria:

• Breast feeding, pregnant or planning to become pregnant during the study
• Within the past 6 months before starting the study you have a history of significant cardiovascular disorder such as unstable angina, congestive heart - failure or acute coronary syndrome
• Currently participating or have participated in a study with an investigational compound or device within the last 30 days
• Has traveled across 3 or more time zones in the last 2 weeks or plans on traveling across 3 or more time zones at any time during the study
• Has done shift work within the past 2 weeks
• Has donated blood products within the last 8 weeks
• Has difficulty sleeping due to a medical condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Suvorexant 10 mg → Placebo; After an ~1- to 2-week single-blind placebo run-in period, participants received 10 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2.	Drug: Suvorexant; oral tablet taken before bedtime; Other Names: MK-4305; Drug: Dose-matched Placebo to Suvorexant; Dose-matched placebo to suvorexant taken before bedtime (oral tablet)
Experimental: Placebo → Suvorexant 10 mg; After an ~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 10 mg suvorexant daily prior to bedtime during Treatment Period 2.	Drug: Suvorexant; oral tablet taken before bedtime; Other Names: MK-4305; Drug: Dose-matched Placebo to Suvorexant; Dose-matched placebo to suvorexant taken before bedtime (oral tablet)
Experimental: Suvorexant 20 mg → Placebo; After an ~1- to 2-week single-blind placebo run-in period, participants received 20 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2.	Drug: Suvorexant; oral tablet taken before bedtime; Other Names: MK-4305; Drug: Dose-matched Placebo to Suvorexant; Dose-matched placebo to suvorexant taken before bedtime (oral tablet)
Experimental: Placebo → Suvorexant 20 mg; After an ~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 20 mg suvorexant daily prior to bedtime during Treatment Period 2.	Drug: Suvorexant; oral tablet taken before bedtime; Other Names: MK-4305; Drug: Dose-matched Placebo to Suvorexant; Dose-matched placebo to suvorexant taken before bedtime (oral tablet)
Experimental: Suvorexant 40 mg → Placebo; After an ~1- to 2-week single-blind placebo run-in period, participants received 40 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2.	Drug: Suvorexant; oral tablet taken before bedtime; Other Names: MK-4305; Drug: Dose-matched Placebo to Suvorexant; Dose-matched placebo to suvorexant taken before bedtime (oral tablet)
Experimental: Placebo → Suvorexant 40 mg; After an ~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 40 mg suvorexant daily prior to bedtime during Treatment Period 2.	Drug: Suvorexant; oral tablet taken before bedtime; Other Names: MK-4305; Drug: Dose-matched Placebo to Suvorexant; Dose-matched placebo to suvorexant taken before bedtime (oral tablet)
Experimental: Suvorexant 80 mg → Placebo; After an ~1- to 2-week single-blind placebo run-in period, participants received 80 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2.	Drug: Suvorexant; oral tablet taken before bedtime; Other Names: MK-4305; Drug: Dose-matched Placebo to Suvorexant; Dose-matched placebo to suvorexant taken before bedtime (oral tablet)
Experimental: Placebo → Suvorexant 80 mg; After an ~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 80 mg suvorexant daily prior to bedtime during Treatment Period 2.	Drug: Suvorexant; oral tablet taken before bedtime; Other Names: MK-4305; Drug: Dose-matched Placebo to Suvorexant; Dose-matched placebo to suvorexant taken before bedtime (oral tablet)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LS Mean Sleep Efficiency (SE) During Periods 1 and 2	SE was defined as total sleep time (TST) in minutes divided by time in bed (measured from lights off to lights on; fixed at 8 hours on each Polysomnography [PSG] night) in minutes, multiplied by 100, where TST is defined as the total time (minutes) in Stages 1, 2, 3, 4 and Rapid Eye Movement (REM). SE= (total sleep time/time in bed) x 100	Night 1 and end of Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2	WASO was defined as the duration of wakefulness measured in minutes (any epoch of Stage 0) from persistent sleep onset (first epoch of the first twenty consecutive epochs of non-wake) to lights on.	Night 1 and end of Week 4
LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2	LPS is defined as the duration of time measured in minutes from lights off to persistent sleep onset.	Night 1 and end of Week 4

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Herring WJ, Snyder E, Budd K, Hutzelmann J, Snavely D, Liu K, Lines C, Roth T, Michelson D. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012 Dec 4;79(23):2265-74. doi: 10.1212/WNL.0b013e31827688ee. Epub 2012 Nov 28.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2008
• Primary Completion (Actual): December 26, 2009
• Study Completion (Actual): December 26, 2009

Study Registration Dates

• First Submitted: November 10, 2008
• First Submitted That Met QC Criteria: November 14, 2008
• First Posted (Estimate): November 17, 2008

Study Record Updates

• Last Update Posted (Actual): November 6, 2018
• Last Update Submitted That Met QC Criteria: October 8, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: 4305-006; 2008_583 (Other Identifier: Merck Registration Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis