Pharmacokinetics of Suvorexant in Participants With Hepatic Insufficiency (MK-4305-017)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatic Insufficiency; Insomnia

Treatments: Drug: Suvorexant

Study type: Interventional

Funder types: Industry

Identifiers

NCT01043926

4305-017

2010_500 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 4 patient groups

Participants with Moderate Hepatic Insufficiency (Part I)

Experimental group

Description:

Participants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study.

Treatment:

Drug: Suvorexant

Healthy Participants (Part I)

Experimental group

Description:

Healthy participants matched to participants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study.

Treatment:

Drug: Suvorexant

Participants with Mild Hepatic Insufficiency (Part II)

Experimental group

Description:

Participants with mild hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part II of the study (if conducted).

Treatment:

Drug: Suvorexant

Healthy Participants (Part II)

Experimental group

Description:

Healthy participants matched to participants with mild hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part II of the study (if conducted).

Treatment:

Drug: Suvorexant