An Open-Label, Single-Dose Study to Investigate the Pharmacokinetics of MK-4305 in Patients With Impaired Renal Function
Overview
- Phase
- Phase 1
- Intervention
- Suvorexant
- Conditions
- Insomnia
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 16
- Primary Endpoint
- Number of Participants Who Discontinued Study Due to an AE
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
Eligibility Criteria
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)
Arms & Interventions
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.
Intervention: Suvorexant
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.
Intervention: Suvorexant
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.
Intervention: Suvorexant
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.
Intervention: Suvorexant
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.
Intervention: Suvorexant
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.
Intervention: Suvorexant
Outcomes
Primary Outcomes
Number of Participants Who Discontinued Study Due to an AE
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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).