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

A Single Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-1064

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.

Study Overview

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

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• 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 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: MK-1064 5 mg; 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.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Experimental: Panel B: MK-1064 10 mg; 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.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Experimental: Panel A: MK-1064 25 mg; 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.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Experimental: Panel B: MK-1064 50 mg; 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.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Experimental: Panel A: MK-1064 100 mg; 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.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Experimental: Panel B: MK-1064 150 mg; 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.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Experimental: Panel A: MK-1064 200 mg; 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.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Experimental: Panel B: MK-1064 250 mg; 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.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Experimental: Panel A: MK-1064 25 mg (Fed); In Period 5, participants received a single MK-1064 dose of 25 mg administered in the evening following a standard high-fat breakfast.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Experimental: Panel B: MK-1064 50 mg (Night); In Period 5, participants received a single MK-1064 dose of 50 mg administered in the evening after a 4-hour fast.	Drug: MK-1064; Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)
Placebo Comparator: Panels A & B: Placebo; 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.	Drug: Placebo; Dose for each period administered as oral placebo tablets matching active MK-1064 tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced One or More 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 study drug, whether or not considered related to the use of study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of study drug, is also an AE.	Up to 14 days after the last dose of study drug (Up to approximately 60 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 study drug, whether or not considered related to the use of study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of study drug, is also an AE.	Up to 14 days after the last dose of study drug (Up to approximately 60 days)
Average Plasma Concentration From Time Zero to 4 Hours (Area Under the Plasma Drug Concentration-time Curve From Time Zero to 4 Hours [AUC0-4hr]) Following Single Doses of MK-1064	AUC0-4hr is the area under the plasma concentration-time curve from time 0 to 4 hours post-dose. This is a measure of the average amount of study drug (MK-1064) in the blood plasma over a period of 4 hours after the dose.	Pre-dose and 0.5, 1, 2, 3 and 4 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Drug Concentration-time Curve From Time Zero to Last Measurable Concentration (AUC0-last) Following Single Doses of MK-1064	AUC0-last is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. It is is a measure of the amount of study drug (MK-1064) in the blood plasma from pre-dose until the last measurable concentration of study drug could be determined.	Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 48 hours post dose (all Periods); 72 hours post-dose (Periods 3 and 4 only)
Maximum Observed Plasma Concentration (Cmax) Following Single Doses of MK-1064	Cmax is the maximum (peak) concentration of study drug (MK-1064) observed in blood plasma.	Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 48 hours post dose (all Periods); 72 hours post dose (Periods 3 and 4 only)
Time to Cmax (Tmax) Following Single Doses of MK-1064	Tmax is the amount of time to reach maximum (peak) plasma drug concentration following drug administration.	Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 48 hours post dose (all Periods); 72 hours post dose (Periods 3 and 4 only)
Apparent Terminal Half-life (t1/2) Following Single Doses of MK-1064	t1/2 is the elimination half-life of study drug. t1/2 is the time it takes for half of the study drug (MK-1064) in the blood plama to dissipate.	Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 48 hours post dose (all Periods); 72 hours post dose (Periods 3 and 4 only)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2009
• Primary Completion (Actual): September 29, 2009
• Study Completion (Actual): September 29, 2009

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: 1064-001

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