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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Polysomnography

Treatments: Drug: MK-1064; Drug: Placebo; Drug: MK-6096

Study type: Interventional

Funder types: Industry

Identifiers

NCT02549027

1064-003

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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20 participants in 4 patient groups

Sequence (MK-1064): 50 mg→250 mg→Placebo→120 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: MK-1064

Drug: MK-6096

Sequence (MK-1064): Placebo→50 mg→120 mg→250 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: MK-1064

Drug: MK-6096

Sequence (MK-1064): 120 mg→Placebo→250 mg→50 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: MK-1064

Drug: MK-6096

Sequence (MK-1064): 250 mg→120 mg→50 mg→Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: MK-1064

Drug: MK-6096