A Single Dose Study of the Safety, Pharmacokinetics and Pharmacodynamics of MK-1064 (MK-1064-001)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Pharmacokinetics

Treatments: Drug: MK-1064; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02549014

1064-001

Details and patient eligibility

About

The purpose of this randomized, double-blind, placebo-controlled study is to evaluate the safety, pharmacokinetics and pharmacodynamics of rising, single oral doses MK-1064 in healthy, young, male participants. The primary pharmacokinetic hypothesis is that at least one dose of MK-1064 that is generally safe and well tolerated produces an average MK-1064 plasma concentration from 0 to 4 hours of ≥2.2 μM. Since this is an early Phase I assessment of MK-1064 in humans, the study protocol allows for modifications to the outlined dose, dosing regimen and/or clinical or laboratory procedures, if required to address study objectives and/or to ensure appropriate safety monitoring of participants.

Full description

Two panels (Panels A and B), will receive alternating single rising oral doses of MK-1064/placebo (i.e., order of administration will be Panel A 5 mg, Panel B 10 mg, Panel A 25 mg, Panel B 50 mg, and continuing in this alternating sequence). Following dosing for a given treatment period, a minimum of 3 days will elapse before administration of the next scheduled dose. After administration of each dose, safety and tolerability will be reviewed. The decision to proceed to the next Panel/Period in the alternating sequence will be contingent on acceptable safety and tolerability data from the preceding Panels/Periods.

Enrollment: 16 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 approximately 6 months

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 legs syndrome, or narcolepsy of any duration
• Participant has experienced poor quality sleep (including difficulty falling asleep, difficulty staying asleep) for at least 4 of 7 nights per week in the past 30 days prior to screening
• Participant works a night shift and is not able to avoid night shift work a minimum of 1 week before each treatment period
• Participant has traveled across 3 or more time zones (transmeridian travel) in the last 2 weeks prior to study
• Unwilling or unable to consume a standard high fat breakfast
• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• History of seizures, epilepsy, stroke, peripheral neuropathy, or other clinically significant neurological disease 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) or participated in another investigational study within 4 weeks prior to screening
• 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
• Is a regular user of sedative-hypnotic agents

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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16 participants in 11 patient groups, including a placebo group

Panel A: MK-1064 5 mg

Experimental group

Description:

Within each of up to 4 treatment periods, 6 participants were randomly assigned to receive single oral doses of MK-1064 5 mg in a fasted state. There was to be a minimum 7-day washout between treatment periods for any given participant.

Treatment:

Drug: MK-1064

Panel B: MK-1064 10 mg

Experimental group

Description:

Within each of up to 4 treatment periods, 6 participants were randomly assigned to receive single oral doses of MK-1064 10 mg in a fasted state. There was to be a minimum 7-day washout between treatment periods for any given participant.

Treatment:

Drug: MK-1064

Panel A: MK-1064 25 mg

Experimental group

Description:

Within each of up to 4 treatment periods, 6 participants were randomly assigned to receive single oral doses of MK-1064 25 mg in a fasted state. There was to be a minimum 7-day washout between treatment periods for any given participant.

Treatment:

Drug: MK-1064

Panel B: MK-1064 50 mg

Experimental group

Description:

Within each of up to 4 treatment periods, 6 participants were randomly assigned to receive single oral doses of MK-1064 50 mg in a fasted state. There was to be a minimum 7-day washout between treatment periods for any given participant.

Treatment:

Drug: MK-1064

Panel A: MK-1064 100 mg

Experimental group

Description:

Within each of up to 4 treatment periods, 6 participants were randomly assigned to receive single oral doses of MK-1064 100 mg in a fasted state. There was to be a minimum 7-day washout between treatment periods for any given participant.

Treatment:

Drug: MK-1064

Panel B: MK-1064 150 mg

Experimental group

Description:

Within each of up to 4 treatment periods, 6 participants were randomly assigned to receive single oral doses of MK-1064 150 mg in a fasted state. There was to be a minimum 7-day washout between treatment periods for any given participant.

Treatment:

Drug: MK-1064

Panel A: MK-1064 200 mg

Experimental group

Description:

Within each of up to 4 treatment periods, 6 participants were randomly assigned to receive single oral doses of MK-1064 200 mg in a fasted state. There was to be a minimum 7-day washout between treatment periods for any given participant.

Treatment:

Drug: MK-1064

Panel B: MK-1064 250 mg

Experimental group

Description:

Within each of up to 4 treatment periods, 6 participants were randomly assigned to receive single oral doses of MK-1064 250 mg in a fasted state. There was to be a minimum 7-day washout between treatment periods for any given participant.

Treatment:

Drug: MK-1064

Panel A: MK-1064 25 mg (Fed)

Experimental group

Description:

In Period 5, participants received a single MK-1064 dose of 25 mg administered in the evening following a standard high-fat breakfast.

Treatment:

Drug: MK-1064

Panel B: MK-1064 50 mg (Night)

Experimental group

Description:

In Period 5, participants received a single MK-1064 dose of 50 mg administered in the evening after a 4-hour fast.

Treatment:

Drug: MK-1064

Panels A & B: Placebo

Placebo Comparator group

Description:

Within each of up to 5 treatment periods, 2 participants were randomly assigned to receive single oral doses of matching placebo in a fasted stated. There was to be a minimum 7-day washout between treatment periods for any given participant.

Treatment:

Drug: Placebo