Clinical trial NCT01043926: Pharmacokinetics of Suvorexant in Participants With Hepatic Insufficiency (MK-4305-017)
Official title: A Single Dose Study to Investigate the Pharmacokinetics of MK-4305 in Patients With Hepatic Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Insomnia
Hepatic Insufficiency
Keywords: Hepatic Insufficiency
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-01-07
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will determine whether the plasma concentration-time profile and pharmacokinetics (PK) of suvorexant (MK-4305) in participants with moderate and mild hepatic insufficiency are similar to those observed in healthy participants.

Detailed description: Study Design:

This study plans to enroll 16 participants in Part I (8 participants with moderate hepatic insufficiency and 8 healthy participants) and 16 participants in Part II (8 participants with mild hepatic insufficiency and 8 healthy participants).

Part II will be conducted only if the primary hypothesis is not met and there is a significant difference in the PK of suvorexant between healthy participants and moderate hepatic insufficiency participants in Part I.

Eligibility criteria: Inclusion Criteria for Hepatic Insufficiency Participants:

* Females of reproductive potential must have a negative pregnancy test and agree to use (and/or have their partner use) two acceptable methods of birth control
* Body Mass Index (BMI) ≤35 kg/m\^2 prior to start of study
* Diagnosis of stable hepatic insufficiency
* Smoking is restricted to ≤10 cigarettes per day

Inclusion Criteria for Healthy Matched Participants:

* Females of reproductive potential must have a negative pregnancy test and agree to use (and/or have their partner use) two acceptable methods of birth control
* BMI within approximately 20% of that of his/her hepatic participant
* Participant is healthy
* Participant is matched by race, gender, age (+/- 5 yrs) to his/her hepatic participant enrolled in the study
* Smoking is restricted to ≤10 cigarettes per day

Exclusion Criteria for Hepatic Insufficiency Participants:

* Participant is mentally or legally incapacitated
* History of a clinically significant psychiatric disorder over the last 5 to 10 years
* Participant has a history of any illness not related to his/her hepatic insufficiency
* History of a persistent sleep abnormality occurring for at least three (3)

months

* Participant has a history of stroke, chronic seizures, or major neurological disorder
* History of clinically significant hematological, immunological, renal,

respiratory, or genitourinary abnormalities, uncomplicated kidney stones or childhood asthma

* History of cancer
* History of cataplexy
* Participant is a nursing mother
* Participant consumes \>3 servings of alcohol a day
* Participant consumes \>6 caffeine servings a day
* History of multiple and/or severe allergies
* Participant is currently using or has history of illegal drug use
* Participant has traveled across 3 or more time zones within 2 weeks of study participation
* Participant works a night shift and is not able to avoid night shift work within 1 week before each treatment visit

Exclusion Criteria for Healthy Matched Participants:

* Participant is mentally or legally incapacitated. History of a clinically significant psychiatric disorder over the last 5 to 10 years.
* Participant has a history of any illness
* History of a persistent sleep abnormality occurring for at least three (3) months
* Participant has a history of stroke, chronic seizures, or major neurological disorder
* History of clinically significant endocrine, gastrointestinal,

cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities, uncomplicated kidney stones or childhood asthma

* History of cancer
* History of cataplexy
* Participant is a nursing mother
* Participant consumes \>3 servings of alcohol a day
* Participant consumes \>6 caffeine servings a day
* History of multiple and/or severe allergies
* Participant is currently using or has history of illegal drug use
* Participant has a history of any chronic and/or active hepatic disease
* Participant has traveled across 3 or more time zones within 2 weeks of study participation
* Participant works a night shift and is not able to avoid night shift work within 1 week before each treatment visit

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-∞) After Single Dose Suvorexant: Moderate Hepatic Insufficiency Participants Versus Healthy Participants (Part I)
timeFrame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
measure: AUC(0-∞) After Single Dose Suvorexant: Mild Hepatic Insufficiency Participants Versus Healthy Participants (Part II)
timeFrame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Suvorexant After Single Dose: Moderate Hepatic Insufficiency Participants Versus Healthy Participants
timeFrame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
measure: Number of Participants With an Adverse Event (AE)
timeFrame: From administration of study drug through 14 days after administration of study drug
measure: Number of Participants Who Discontinued Study Due to an AE
timeFrame: From administration of study drug through 14 days after administration of study drug
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References: