Pharmacokinetics of Suvorexant in Participants With Impaired Renal Function (MK-4305-023)(COMPLETED)

An Open-Label, Single-Dose Study to Investigate the Pharmacokinetics of MK-4305 in Patients With Impaired Renal Function

This study will investigate whether the plasma concentration-time profile and pharmacokinetics (PK) of suvorexant (MK-4305) in participants with impaired renal function are similar to those observed in healthy participants; and will evaluate the safety and tolerability of suvorexant both in participants with impaired renal function and in healthy participants.

Study Overview

• Status: Completed
• Conditions: Insomnia
• Intervention / Treatment: Drug: Suvorexant

Detailed Description

Study Design:

This study plans to enroll 16 participants in Part I (8 participants with severe renal impairment and a control group of 8 healthy participants) and 32 participants in Part II (8 participants with moderate renal impairment and a control group of 8 healthy participants; and 8 participants with mild renal impairment and a control group of 8 healthy participants).

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

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Impaired Renal Function 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) ≤40 kg/m^2
• Diagnosis of renal insufficiency

Healthy 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) ≤40 kg/m^2 and is matched for BMI ± 5 units to his/her corresponding renal participant
• In general good health
• Matched for age ± 10 years to his/her corresponding renal participant

Exclusion Criteria:

Impaired Renal Function Participants:

• Is mentally or legally incapacitated
• History of a clinically significant psychiatric disorder over the last year
• Has rapidly fluctuating renal function or has demonstrated or suspected renal artery stenosis
• Has had a kidney transplant
• Unstable endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases
• History of cancer (Some exceptions apply)
• Regular user of barbiturates or sleep aides
• Consumes excessive amounts of alcohol (>2 drinks/day)
• Consumes excessive amounts of caffeinated beverages (>6/day)
• Has had major surgery within 4 weeks
• Has a history of significant multiple and/or severe allergies
• Has a history of cataplexy
• Participant works a night shift and is not able to avoid night shift work during the study
• Current or history of illicit drug abuse
• Nursing mothers

Healthy Participants:

• Is mentally or legally incapacitated;
• Has a history of stroke, chronic seizures, or major neurological disorder
• Unstable endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases
• History of cancer (Some exceptions apply)
• Regular user of barbiturates or sleep aides
• Consumes excessive amounts of alcohol (>2 drinks/day)
• Consumes excessive amounts of caffeinated beverages (>6/day)
• Has had major surgery within 4 weeks
• Has a history of significant multiple and/or severe allergies
• Has a history of cataplexy
• Participant works a night shift and is not able to avoid night shift work during the study
• Current or history of illicit drug abuse
• Nursing mothers

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with Severe Renal Impairment (Part I); Participants with severe renal impairment will receive a single dose of 20 mg open-label suvorexant during Part I of the study.	Drug: Suvorexant; single oral dose of 20 mg (administered as 2 x 10 mg tablets) of suvorexant administered with ~240 mL of water after an 8 hour fast; Other Names: MK-4305
Experimental: Healthy Participants (Severe Impairment Controls) (Part I); Healthy participants matched to participants with severe renal impairment will receive a single dose of 20 mg open-label suvorexant during Part I of the study.	Drug: Suvorexant; single oral dose of 20 mg (administered as 2 x 10 mg tablets) of suvorexant administered with ~240 mL of water after an 8 hour fast; Other Names: MK-4305
Experimental: Participants with Moderate Renal Impairment (Part II); Participants with moderate renal impairment will receive a single dose of 20 mg open-label suvorexant during Part II of the study.	Drug: Suvorexant; single oral dose of 20 mg (administered as 2 x 10 mg tablets) of suvorexant administered with ~240 mL of water after an 8 hour fast; Other Names: MK-4305
Experimental: Healthy Participants (Moderate Impairment Controls) (Part II); Healthy participants matched to participants with moderate renal impairment will receive a single dose of 20 mg open-label suvorexant during Part II of the study.	Drug: Suvorexant; single oral dose of 20 mg (administered as 2 x 10 mg tablets) of suvorexant administered with ~240 mL of water after an 8 hour fast; Other Names: MK-4305
Experimental: Participants with Mild Renal Impairment (Part II); Participants with mild renal impairment will receive a single dose of 20 mg open-label suvorexant during Part II of the study.	Drug: Suvorexant; single oral dose of 20 mg (administered as 2 x 10 mg tablets) of suvorexant administered with ~240 mL of water after an 8 hour fast; Other Names: MK-4305
Experimental: Healthy Participants (Mild Impairment Controls) (Part II); Healthy participants matched to participants with mild renal impairment will receive a single dose of 20 mg open-label suvorexant during Part II of the study.	Drug: Suvorexant; single oral dose of 20 mg (administered as 2 x 10 mg tablets) of suvorexant administered with ~240 mL of water after an 8 hour fast; Other Names: MK-4305

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-∞) After Single Dose Suvorexant: Severe Renal Impairment 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 the extrapolated area given by the quotient of the last detectable concentration and the apparent terminal rate constant (λ).	Predose and 0.5, 1, 2, 4, 6, 9, 12, 16, 24, 48, 72, 96, and 120 hours post-dose
AUC(0-∞) After Single Dose Suvorexant: Moderate and Mild Renal Impairment 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 the extrapolated area given by the quotient of the last detectable concentration and the apparent terminal rate constant (λ).	Predose and 0.5, 1, 2, 4, 6, 9, 12, 16, 24, 48, 72, 96, and 120 hours post-dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2010
• Primary Completion (Actual): July 15, 2010
• Study Completion (Actual): July 15, 2010

Study Registration Dates

• First Submitted: January 28, 2010
• First Submitted That Met QC Criteria: January 28, 2010
• First Posted (Estimate): February 1, 2010

Study Record Updates

• Last Update Posted (Actual): November 6, 2018
• Last Update Submitted That Met QC Criteria: October 8, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal 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: 4305-023; 2010_505 (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