A Study to Evaluate the Effects of Single Doses of MK-1064 and MK-6096 on Polysomnography (PSG) (MK-1064-003)

A Crossover Study to Evaluate the Effects of Single Doses of MK-1064 and MK-6096 on Polysomnography (PSG)

The purpose of this randomized, double-blind, placebo-controlled, 5-period crossover study is to assess the effect of single oral doses of MK-1064 on latency to persistent sleep (LPS) as measured by polysomnography (PSG) in healthy young male participants, and to evaluate the safety and tolerability of single oral doses of MK-1064 and MK-6096 in healthy young male participants. The primary efficacy hypothesis is that at least one dose of MK-1064 is superior to placebo in decreasing LPS in healthy male participants as assessed by PSG.

Study Overview

• Status: Completed
• Conditions: Polysomnography
• Intervention / Treatment: Drug: MK-1064; Drug: MK-6096; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body Mass Index (BMI) ≤31 kg/m^2
• In good health based on medical history, physical examination, vital sign measurements, and laboratory safety tests
• Nonsmoker and has not used nicotine or nicotine-containing products for at least 6 months
• No history of any sleep disorder
• Has not used prescription or over the counter sedation or alerting medication in 4 weeks prior to screening
• Participant has a usual bedtime between 8:00 PM and 12:00 AM
• Participant has total sleep duration of ≥6.5 and ≤9 hours during the 4 weeks prior to screening
• Male participants with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug

Exclusion Criteria:

• Mentally or legally incapacitated, significant emotional problems at screening or expected during the conduct of the study or history of a clinically significant psychiatric disorder within the last 10 years
• History of any persistent sleep abnormality (including difficulty falling asleep, difficulty staying asleep) lasting for 3 months or more, or history of obstructive sleep apnea, restless leg syndrome, or narcolepsy
• History of clinically significant sleep disorders within the last 5 years
• History of circadian rhythm sleep disorder, clinically important parasomnia, or primary insomnia
• History of repeated falls or fractures secondary to falling within the past 2 years
• Participant works a night shift and is not able to avoid night shift work a minimum of 1 week prior to screening and for the duration of the study
• Participant has traveled across 3 or more time zones (transmeridian travel) in the last 2 weeks prior to study
• Is a regular user of sedative-hypnotic agents
• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• History of stroke, peripheral neuropathy, chronic seizures or other clinically significant neurological disorder or cognitive impairment
• History of cancer
• History of cataplexy
• Participant is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies, beginning approximately 2 weeks prior to administration of the initial dose of study drug and throughout the study
• Participant consumes >3 servings of alcohol a day
• Participant consumes >6 caffeine servings a day
• Participant has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening, or participated in another investigational study within 3 months prior to first dose of study drug
• History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Is currently a regular user of any illicit drugs or has a history of drug (including alcohol) abuse within 2 years of screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence (MK-1064): 50 mg→250 mg→Placebo→120 mg; For overall study population, 5 participants each were to be allocated to one of 4 sequences. In this sequence, participants received the following: Period 1 - single dose of 50 mg MK-1064, Period 2 - single dose of 250 mg MK-1064, Period 3 - single dose of placebo, Period 4 - single dose of 120 mg MK-1064. Participants completing the first 4 periods also were to receive the following: Period 5 - single dose of 20 mg MK-6096 or placebo, in an 18:2 ratio for overall study population, according to separate allocation. There was a minimum 7-day washout between doses.	Drug: MK-1064; Oral MK-1064 tablets (10 and 50 mg strengths); Drug: MK-6096; Oral MK-6096 tablets (5 mg strength); Drug: Placebo; Oral placebo tablets (matching active MK-1064 tablets, matching active MK-6096 tablets)
Experimental: Sequence (MK-1064): Placebo→50 mg→120 mg→250 mg; For overall study population, 5 participants each were to be allocated to one of 4 sequences. In this sequence, participants received the following: Period 1 - single dose of placebo, Period 2 - single dose of 50 mg MK-1064, Period 3 - single dose of 120 mg MK-1064, Period 4 - single dose of 250 mg MK-1064. Participants completing the first 4 periods also were to receive the following: Period 5 - single dose of 20 mg MK-6096 or placebo, in an 18:2 ratio for overall study population, according to separate allocation. There was a minimum 7-day washout between doses.	Drug: MK-1064; Oral MK-1064 tablets (10 and 50 mg strengths); Drug: MK-6096; Oral MK-6096 tablets (5 mg strength); Drug: Placebo; Oral placebo tablets (matching active MK-1064 tablets, matching active MK-6096 tablets)
Experimental: Sequence (MK-1064): 120 mg→Placebo→250 mg→50 mg; For overall study population, 5 participants each were to be allocated to one of 4 sequences. In this sequence, participants received the following: Period 1 - single dose of 120 mg MK-1064, Period 2 - single dose of placebo, Period 3 - single dose of 250 mg MK-1064, Period 4 - single dose of 50 mg MK-1064. Participants completing the first 4 periods also were to receive the following: Period 5 - single dose of 20 mg MK-6096 or placebo, in an 18:2 ratio for overall study population, according to separate allocation. There was a minimum 7-day washout between doses.	Drug: MK-1064; Oral MK-1064 tablets (10 and 50 mg strengths); Drug: MK-6096; Oral MK-6096 tablets (5 mg strength); Drug: Placebo; Oral placebo tablets (matching active MK-1064 tablets, matching active MK-6096 tablets)
Experimental: Sequence (MK-1064): 250 mg→120 mg→50 mg→Placebo; For overall study population, 5 participants each were to be allocated to one of 4 sequences. In this sequence, participants received the following: Period 1 - single dose of 250 mg MK-1064, Period 2 - single dose of 120 mg MK-1064, Period 3 - single dose of 50 mg MK-1064, Period 4 - single dose of placebo. Participants completing the first 4 periods also were to receive the following: Period 5 - single dose of 20 mg MK-6096 or placebo, in an 18:2 ratio for overall study population, according to separate allocation. There was a minimum 7-day washout between doses.	Drug: MK-1064; Oral MK-1064 tablets (10 and 50 mg strengths); Drug: MK-6096; Oral MK-6096 tablets (5 mg strength); Drug: Placebo; Oral placebo tablets (matching active MK-1064 tablets, matching active MK-6096 tablets)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Latency to Persistent Sleep (LPS) Following Single Doses of MK-1064 and Placebo	LPS is measured during overnight sleep laboratory (polysomnography [PSG]) assessment and is defined as the duration of time from the beginning of PSG assessment to the first interval of 10 consecutive minutes of sleep.	1 to 9 hours post dose, within each treatment period
LPS Following Single Doses of MK-6096 and Placebo	LPS is measured during overnight sleep laboratory (PSG) assessment and is defined as the duration of time from the beginning of PSG assessment to the first interval of 10 consecutive minutes of sleep.	1 to 9 hours post dose, within each treatment period
Number of Participants With Adverse Events (AEs)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. 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 study drug, is also an AE.	Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Number of Participants Who Discontinued Study Due to an AE	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. 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 study drug, is also an AE.	Up to 14 days after the last dose of study drug (Up to approximately 42 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wake Time After Sleep Onset (WASO) Following Single Doses of MK-1064 and Placebo	WASO is measured during overnight sleep laboratory (PSG) assessment and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning.	1 to 9 hours post dose, within each treatment period
WASO Following Single Doses of MK-6096 and Placebo	WASO is measured during overnight sleep laboratory (PSG) assessment and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning.	1 to 9 hours post dose, within each treatment period
Change From Baseline in Choice Reaction Time (CRT) Following Single Doses of MK-1064 and Placebo	CRT assessment used in this study is a two-choice, computer-controlled test in which the participant responds to stimulus words presented on the screen of a laptop computer. During the test either the word "NO" or the word "YES" is presented on the screen and the participant is instructed to press the corresponding button as quickly as possible. There are 50 trials for which each stimulus word is chosen randomly with equal probability and there is a varying inter-stimulus interval. The mean reaction time of accurate responses is determined. The assessment is performed pre-dose and at 10 hours post dose. The outcome measure is change from baseline to post dose in reaction time.	Pre-dose and 10 hours post dose, within each treatment period
Change From Baseline in CRT Following Single Doses of MK-6096 and Placebo	CRT assessment used in this study is a two-choice, computer-controlled test in which the participant responds to stimulus words presented on the screen of a laptop computer. During the test either the word "NO" or the word "YES" is presented on the screen and the participant is instructed to press the corresponding button as quickly as possible. There are 50 trials for which each stimulus word is chosen randomly with equal probability and there is a varying inter-stimulus interval. The mean reaction time of accurate responses is determined. The assessment is performed pre-dose and at 10 hours post dose. The outcome measure is change from baseline to post dose in reaction time.	Pre-dose and 10 hours post dose, within each treatment period

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2009
• Primary Completion (Actual): April 6, 2010
• Study Completion (Actual): April 6, 2010

Study Registration Dates

• First Submitted: September 11, 2015
• First Submitted That Met QC Criteria: September 11, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): October 23, 2018
• Last Update Submitted That Met QC Criteria: September 24, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 1064-003

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