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

Phase 1

Completed

• Conditions: Hepatic Insufficiency; Insomnia
• Interventions: Drug: Suvorexant

• Registration Number: NCT01043926
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Study Timeline

• Study First Submitted: 2010-01-05
• Study First Submitted QC: 2010-01-06
• Study First Posted: 2010-01-07
• Study Start: 2010-02-22
• Primary Completion: 2010-04-14
• Study Completion: 2010-04-14
• Results First Submitted: 2014-08-19
• Results First Submitted QC: 2014-08-19
• Results First Posted: 2014-08-29
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-21
• Last Update Posted: 2018-09-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Participants with Moderate Hepatic Insufficiency (Part I)	Suvorexant	Participants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study.
Healthy Participants (Part I)	Suvorexant	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.
Participants with Mild Hepatic Insufficiency (Part II)	Suvorexant	Participants with mild hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part II of the study (if conducted).
Healthy Participants (Part II)	Suvorexant	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).

Primary Outcome Measures

Name	Time	Method
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)	Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose	Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]). AUC(0-∞) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC\[0-last\]) and Ct/λ, where Ct was the last measurable concentration and λ was the apparent terminal rate constant.
AUC(0-∞) After Single Dose Suvorexant: Mild Hepatic Insufficiency Participants Versus Healthy Participants (Part II)	Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose	Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]). AUC(0-∞) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC\[0-last\]) and Ct/λ, where Ct was the last measurable concentration and λ was the apparent terminal rate constant.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With an Adverse Event (AE)	From administration of study drug through 14 days after administration of study drug	An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.
Maximum Plasma Concentration (Cmax) of Suvorexant After Single Dose: Moderate Hepatic Insufficiency Participants Versus Healthy Participants	Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose	Cmax was defined as the maximum observed concentration of a drug after administration.
Number of Participants Who Discontinued Study Due to an AE	From administration of study drug through 14 days after administration of study drug	An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.