Clinical trial NCT02549014: A Single Dose Study of the Safety, Pharmacokinetics and Pharmacodynamics of MK-1064 (MK-1064-001)
Official title: A Single Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-1064
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-09-14
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to 14 days after the last dose of study drug (Up to approximately 60 days)
measure: Number of Participants Who Discontinued Study Due to an AE
timeFrame: Up to 14 days after the last dose of study drug (Up to approximately 60 days)
measure: 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
timeFrame: Pre-dose and 0.5, 1, 2, 3 and 4 hours post-dose
Secondary outcomes:
measure: Area Under the Plasma Drug Concentration-time Curve From Time Zero to Last Measurable Concentration (AUC0-last) Following Single Doses of MK-1064
timeFrame: 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)
measure: Maximum Observed Plasma Concentration (Cmax) Following Single Doses of MK-1064
timeFrame: 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)
measure: Time to Cmax (Tmax) Following Single Doses of MK-1064
timeFrame: 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)
measure: Apparent Terminal Half-life (t1/2) Following Single Doses of MK-1064
timeFrame: 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)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: