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

A Single Dose Study to Investigate the Pharmacokinetics of MK-4305 in Patients With Hepatic Insufficiency

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency; Insomnia
• Intervention / Treatment: Drug: Suvorexant

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with Moderate Hepatic Insufficiency (Part I); Participants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study.	Drug: Suvorexant; single 20 mg dose of suvorexant will be administered as 2 x 10 mg film coated tablets on Day 1 after an overnight fast with water.; Other Names: MK-4305
Experimental: Healthy Participants (Part I); 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.	Drug: Suvorexant; single 20 mg dose of suvorexant will be administered as 2 x 10 mg film coated tablets on Day 1 after an overnight fast with water.; Other Names: MK-4305
Experimental: Participants with Mild Hepatic Insufficiency (Part II); Participants with mild hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part II of the study (if conducted).	Drug: Suvorexant; single 20 mg dose of suvorexant will be administered as 2 x 10 mg film coated tablets on Day 1 after an overnight fast with water.; Other Names: MK-4305
Experimental: Healthy Participants (Part II); 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).	Drug: Suvorexant; single 20 mg dose of suvorexant will be administered as 2 x 10 mg film coated tablets on Day 1 after an overnight fast with water.; Other Names: MK-4305

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
AUC(0-∞) After Single Dose Suvorexant: Mild Hepatic Insufficiency Participants Versus Healthy Participants (Part II)	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.	Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Suvorexant After Single Dose: Moderate Hepatic Insufficiency Participants Versus Healthy Participants	Cmax was defined as the maximum observed concentration of a drug after administration.	Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
Number of Participants With an Adverse Event (AE)	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.	From administration of study drug through 14 days after administration of study drug
Number of Participants Who Discontinued Study Due to an AE	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.	From administration of study drug through 14 days after administration of study drug

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2010
• Primary Completion (Actual): April 14, 2010
• Study Completion (Actual): April 14, 2010

Study Registration Dates

• First Submitted: January 5, 2010
• First Submitted That Met QC Criteria: January 6, 2010
• First Posted (Estimate): January 7, 2010

Study Record Updates

• Last Update Posted (Actual): September 21, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Hepatic Insufficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: 4305-017; 2010_500 (Other Identifier: Merck Registration Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis