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

Phase 1

Completed

• Conditions: Insomnia
• Interventions: Drug: Suvorexant

• Registration Number: NCT01059851
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

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 Timeline

• Study First Submitted: 2010-01-28
• Study First Submitted QC: 2010-01-28
• Study First Posted: 2010-02-01
• Study Start: 2010-05-24
• Primary Completion: 2010-07-15
• Study Completion: 2010-07-15
• Results First Submitted: 2014-08-19
• Results First Submitted QC: 2014-08-19
• Results First Posted: 2014-08-29
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-08
• Last Update Posted: 2018-11-06

Recruitment & Eligibility

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

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Participants with Severe Renal Impairment (Part I)	Suvorexant	Participants with severe renal impairment will receive a single dose of 20 mg open-label suvorexant during Part I of the study.
Healthy Participants (Severe Impairment Controls) (Part I)	Suvorexant	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.
Healthy Participants (Moderate Impairment Controls) (Part II)	Suvorexant	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.
Participants with Mild Renal Impairment (Part II)	Suvorexant	Participants with mild renal impairment will receive a single dose of 20 mg open-label suvorexant during Part II of the study.
Healthy Participants (Mild Impairment Controls) (Part II)	Suvorexant	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.
Participants with Moderate Renal Impairment (Part II)	Suvorexant	Participants with moderate renal impairment will receive a single dose of 20 mg open-label suvorexant during Part II of the study.

Primary Outcome Measures

Name	Time	Method
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.
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.
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)	Predose and 0.5, 1, 2, 4, 6, 9, 12, 16, 24, 48, 72, 96, and 120 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 the extrapolated area given by the quotient of the last detectable concentration and the apparent terminal rate constant (λ).
AUC(0-∞) After Single Dose Suvorexant: Moderate and Mild Renal Impairment Participants Versus Healthy Participants (Part II)	Predose and 0.5, 1, 2, 4, 6, 9, 12, 16, 24, 48, 72, 96, and 120 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 the extrapolated area given by the quotient of the last detectable concentration and the apparent terminal rate constant (λ).