Polysomnography Study of MK-6096 in Participants With Primary Insomnia (MK-6096-011)

A Phase IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 2-Period Adaptive Crossover Polysomnography Study to Evaluate the Safety and Efficacy of MK-6096 in Patients With Primary Insomnia

This was a cross-over, polysomnography (PSG) study to test the safety, tolerability and effectiveness of different doses of MK-6096 in the treatment of participants with primary insomnia. The primary efficacy hypothesis was that at least one dose of MK-6096 is superior to placebo in improving sleep efficiency (SE) as measured by PSG on Night 1 and at the end of 4 weeks of treatment (Week 4).

Study Overview

• Status: Completed
• Conditions: Primary Insomnia
• Intervention / Treatment: Drug: MK-6096; Drug: Dose-matched Placebo to MK-6096

• Study Type: Interventional
• Enrollment (Actual): 326
• 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:

• Participant is willing to stay overnight at a sleep laboratory on 6 separate nights and is willing to stay in bed for at least 8 hours each night while at the sleep laboratory
• Participant's regular bedtime is between 9 PM and 12 AM (midnight)
• Participant is able to read and complete questionnaires and diaries
• Participant is willing to refrain from napping during the study

Exclusion Criteria:

• If female, participant is breast feeding, pregnant, or planning to become pregnant
• Participant is expecting to donate eggs or sperm during the study
• Participant has any history of a neurological disorder
• Participant has a history within the past 6 months of a cardiovascular disorder such as unstable angina, congestive heart failure or acute coronary syndrome.
• Participant has difficulty sleeping due to a medical condition
• Participant has donated blood products within the 8 weeks prior to the study
• Participant plans to travel across 3 or more time zones during the study
• Participant is currently participating or has participated in a study with an investigational compound or device within the last 30 days

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: MK-6096 2.5 mg/Placebo; Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive MK-6096 2.5 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory on Days 1 and 29 for overnight polysomnography (PSG) recordings, on which days they receive MK-6096 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment for the remaining 11 days. During Treatment Period 2, participants receive dose-matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive placebo 30 minutes before bedtime.	Drug: MK-6096; MK-6096 2.5 mg or 5 mg tablets equaling 2.5 mg dose, 5 mg dose, 10 mg dose, or 20 mg dose (depending upon allocation) were taken daily before bedtime for 4 weeks.; Drug: Dose-matched Placebo to MK-6096; Dose-matched placebo tablets to MK-6096 were taken daily before bedtime during 2-week single-blind run-in, for 4 weeks as a treatment period, and during 2-week washout between treatment periods.
Experimental: Placebo/MK-6096 2.5 mg; Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29, on which days they receive placebo 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment for the remaining 11 days. During Treatment Period 2, participants receive MK-6096 2.5 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive MK-6096 30 minutes before bedtime.	Drug: MK-6096; MK-6096 2.5 mg or 5 mg tablets equaling 2.5 mg dose, 5 mg dose, 10 mg dose, or 20 mg dose (depending upon allocation) were taken daily before bedtime for 4 weeks.; Drug: Dose-matched Placebo to MK-6096; Dose-matched placebo tablets to MK-6096 were taken daily before bedtime during 2-week single-blind run-in, for 4 weeks as a treatment period, and during 2-week washout between treatment periods.
Experimental: MK-6096 5 mg/Placebo; Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive MK-6096 5 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory on Days 1 and 29 for 2 overnight PSG recordings, on which days they receive MK-6096 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo to MK-6096 for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive placebo 30 minutes before bedtime.	Drug: MK-6096; MK-6096 2.5 mg or 5 mg tablets equaling 2.5 mg dose, 5 mg dose, 10 mg dose, or 20 mg dose (depending upon allocation) were taken daily before bedtime for 4 weeks.; Drug: Dose-matched Placebo to MK-6096; Dose-matched placebo tablets to MK-6096 were taken daily before bedtime during 2-week single-blind run-in, for 4 weeks as a treatment period, and during 2-week washout between treatment periods.
Experimental: Placebo/MK-6096 5 mg; Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29, on which days they receive placebo 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive MK-6096 5 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive MK-6096 30 minutes before bedtime.	Drug: MK-6096; MK-6096 2.5 mg or 5 mg tablets equaling 2.5 mg dose, 5 mg dose, 10 mg dose, or 20 mg dose (depending upon allocation) were taken daily before bedtime for 4 weeks.; Drug: Dose-matched Placebo to MK-6096; Dose-matched placebo tablets to MK-6096 were taken daily before bedtime during 2-week single-blind run-in, for 4 weeks as a treatment period, and during 2-week washout between treatment periods.
Experimental: MK-6096 10 mg/Placebo; Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive MK-6096 10 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory on Days 1 and 29 for 2 overnight PSG recordings, on which days they receive MK-6096 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo to MK-6096 for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive placebo 30 minutes before bedtime.	Drug: MK-6096; MK-6096 2.5 mg or 5 mg tablets equaling 2.5 mg dose, 5 mg dose, 10 mg dose, or 20 mg dose (depending upon allocation) were taken daily before bedtime for 4 weeks.; Drug: Dose-matched Placebo to MK-6096; Dose-matched placebo tablets to MK-6096 were taken daily before bedtime during 2-week single-blind run-in, for 4 weeks as a treatment period, and during 2-week washout between treatment periods.
Experimental: Placebo/MK-6096 10 mg; Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29, on which days they receive placebo 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive MK-6096 10 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive MK-6096 30 minutes before bedtime.	Drug: MK-6096; MK-6096 2.5 mg or 5 mg tablets equaling 2.5 mg dose, 5 mg dose, 10 mg dose, or 20 mg dose (depending upon allocation) were taken daily before bedtime for 4 weeks.; Drug: Dose-matched Placebo to MK-6096; Dose-matched placebo tablets to MK-6096 were taken daily before bedtime during 2-week single-blind run-in, for 4 weeks as a treatment period, and during 2-week washout between treatment periods.
Experimental: MK-6096 20 mg/Placebo; Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive MK-6096 20 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory on Days 1 and 29 for 2 overnight PSG recordings, on which days they receive MK-6096 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo to MK-6096 for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive placebo 30 minutes before bedtime.	Drug: MK-6096; MK-6096 2.5 mg or 5 mg tablets equaling 2.5 mg dose, 5 mg dose, 10 mg dose, or 20 mg dose (depending upon allocation) were taken daily before bedtime for 4 weeks.; Drug: Dose-matched Placebo to MK-6096; Dose-matched placebo tablets to MK-6096 were taken daily before bedtime during 2-week single-blind run-in, for 4 weeks as a treatment period, and during 2-week washout between treatment periods.
Experimental: Placebo/MK-6096 20 mg; Prior to Treatment Period 1, participants undergo a 3 week screening period and receive single-blind placebo for the last 2 weeks if screening criteria are met. During Treatment Period 1, participants receive matched placebo to MK-6096 daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29, on which days they receive placebo 30 minutes before bedtime. Treatment Period 1 is followed by a 2-week washout period during which the participant receives single-blind placebo for the first 3 days and no treatment the remaining 11 days. During Treatment Period 2, participants receive MK-6096 20 mg daily for 4 weeks at 5-10 minutes before bedtime and return to the sleep laboratory for 2 overnight PSG recordings on Days 1 and 29 (Study Days 44 and 72), on which days they receive MK-6096 30 minutes before bedtime.	Drug: MK-6096; MK-6096 2.5 mg or 5 mg tablets equaling 2.5 mg dose, 5 mg dose, 10 mg dose, or 20 mg dose (depending upon allocation) were taken daily before bedtime for 4 weeks.; Drug: Dose-matched Placebo to MK-6096; Dose-matched placebo tablets to MK-6096 were taken daily before bedtime during 2-week single-blind run-in, for 4 weeks as a treatment period, and during 2-week washout between treatment periods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Efficiency (SE) on Night 1 and After 4 Weeks of Treatment	SE was measured using a polysomnogram (PSG), which consisted of an electroencephalogram (EEG) for registration of brain activity during sleep, an electro-oculogram (EOG) for registration of the eye movements during sleep, and an electromyogram (EMG) for recording chin muscle activity during sleep. Sleep stage scoring was performed visually in 30-second epochs according to Rechtschaffen and Kales (R&K) criteria and PSG data were read by a Central Reader. 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 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. Least squares (LS) mean SE was reported for each treatment arm.	Night 1 and end of Week 4
Percentage of Participants With at Least One Adverse Event (AE) During Treatment Periods 1 and 2	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. The percentage of participants with AEs are presented for the first day of randomized treatment dosing (Day 1) through the last day of randomized treatment dosing (Day 29) in Treatment Periods 1 and 2.	Day 1 through Day 29 in Treatment Periods 1 and 2 (58 days total)
Percentage of Participants That Discontinued Study Medication Due to an AE During Treatment Periods 1 and 2	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. The percentage of participants that discontinued study medication due to AEs are presented for the first day of randomized treatment dosing (Day 1) through the last day of randomized treatment dosing (Day 29) in Treatment Periods 1 and 2.	Day 1 through Day 29 in Treatment Periods 1 and 2 (58 days total)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wake After Persistent Sleep Onset (WASO) on Night 1 and After 4 Weeks of Treatment	WASO was measured using a PSG, which consisted of an EEG for registration of brain activity during sleep, an EOG for registration of the eye movements during sleep, and an EMG for recording chin muscle activity during sleep. Sleep stage scoring was performed visually in 30-second epochs according to R&K criteria and PSG data were read by a Central Reader. 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. LS mean WASO was reported for each treatment arm.	Night 1 and end of Week 4
Latency to the Onset of Persistent Sleep (LPS) on Night 1 and After 4 Weeks of Treatment	LPS was measured using a PSG, which consisted of an EEG for registration of brain activity during sleep, an EOG for registration of the eye movements during sleep, and an EMG for recording chin muscle activity during sleep. Sleep stage scoring was performed visually in 30-second epochs according to R&K criteria and PSG data were read by a Central Reader. LPS was defined as the duration of time measured in minutes from lights off to persistent sleep onset. An epoch of non-wake was defined as a 30-second interval classified as either Stage 1, 2, 3, 4 or REM according to conventional R&K scoring. LS mean LPS was reported for each treatment arm.	Night 1 and end of Week 4

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Connor KM, Mahoney E, Jackson S, Hutzelmann J, Zhao X, Jia N, Snyder E, Snavely D, Michelson D, Roth T, Herring WJ. A Phase II Dose-Ranging Study Evaluating the Efficacy and Safety of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Primary Insomnia. Int J Neuropsychopharmacol. 2016 Aug 12;19(8):pyw022. doi: 10.1093/ijnp/pyw022. Print 2016 Aug.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: November 25, 2009
• First Submitted That Met QC Criteria: November 25, 2009
• First Posted (Estimate): November 30, 2009

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
• Other Study ID Numbers: 6096-011; MK-6096-011 (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