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

NCT02549014 | Completed Phase 1 Results

• 1 other identifier: 1064-001
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Area Under the Plasma Drug Concentration-time Curve From Time Zero to Last Measurable Concentration (AUC0-last) Following Single Doses of MK-1064

  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

  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

  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

  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)

Study Arms (11)

Panel A: MK-1064 5 mg

EXPERIMENTAL

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

Panel B: MK-1064 10 mg

EXPERIMENTAL

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

Panel A: MK-1064 25 mg

EXPERIMENTAL

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

Panel B: MK-1064 50 mg

EXPERIMENTAL

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

Panel A: MK-1064 100 mg

EXPERIMENTAL

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

Panel B: MK-1064 150 mg

EXPERIMENTAL

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

Panel A: MK-1064 200 mg

EXPERIMENTAL

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

Panel B: MK-1064 250 mg

EXPERIMENTAL

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

Panel A: MK-1064 25 mg (Fed)

EXPERIMENTAL

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

Panel B: MK-1064 50 mg (Night)

EXPERIMENTAL

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

Panels A & B: Placebo

PLACEBO COMPARATOR

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

Interventions

MK-1064 DRUG

Dose for each period administered as oral MK-1064 tablets (1, 10 and 50 mg strengths)

Panel A: MK-1064 100 mg; Panel A: MK-1064 200 mg; Panel A: MK-1064 25 mg; Panel A: MK-1064 25 mg (Fed); Panel A: MK-1064 5 mg; Panel B: MK-1064 10 mg; Panel B: MK-1064 150 mg; Panel B: MK-1064 250 mg; Panel B: MK-1064 50 mg; Panel B: MK-1064 50 mg (Night)

Placebo DRUG

Dose for each period administered as oral placebo tablets matching active MK-1064 tablets

Panels A & B: Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2015
• First Posted: September 14, 2015
• Study Start: July 6, 2009
• Primary Completion: September 29, 2009
• Study Completion: September 29, 2009
• Last Updated: October 23, 2018
• Results First Posted: January 21, 2016

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share