A Study of MK-0616 in Participants With Moderate Renal Impairment (MK-0616-007)

Study Overview
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Brief Summary
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This purpose of this study is to compare the pharmacokinetics (PK) of a single dose of MK-0616 in participants with moderate renal impairment (RI) to those of healthy matched control participants. This study is being conducted to assess the impact of moderate renal insufficiency on the PK of MK-0616.

Official Title
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An Open-Label Clinical Study to Evaluate the Pharmacokinetics of MK-0616 Following Administration of a Single Dose to Participants With Moderate Renal Impairment

Conditions
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Moderate Renal Impairment

Intervention / Treatment
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* Drug: MK-0616


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Good health based upon medical history, physical examination, vital signs, laboratory safety tests, and electrocardiograms (ECG) performed before randomization. Body mass index (BMI) ≥18 kg/m^2 and ≤40 kg/m^2. Male participants must agree to the following during the intervention period and for at least 90 days after the last dose of study intervention: Refrain from donating sperm, PLUS either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent, or use acceptable contraception per study protocol. Female participants must be of non-childbearing potential. Moderate RI participants: Baseline estimated glomerular filtration rate (eGFR) ≥30 and <60 mL/min/1.73 m^2 based on the Modification of Diet in Renal Disease (MDRD) equation. Moderate RI participants: No clinically significant change in renal status at least 1 month prior to dosing and not currently receiving or has not previously been on hemodialysis. Healthy Matched Controls: eGFR ≥80 mL/min/1.73 m^2 based on the MDRD equation. Exclusion Criteria: Healthy Matched Controls: history of clinically significant endocrine, GI, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator. History of cancer, with the exception of adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies that have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study. History of significant multiple and/or severe allergies. Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV). History of major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit. Moderate RI participants: Does not agree to follow the smoking restrictions as defined by the study. Healthy Matched Controls: History of smoking and/or has used nicotine or nicotine-containing products (eg, nicotine patch and electronic cigarette) within 3 months of screening. Received any nonlive vaccine starting from 14 days prior to study intervention or is scheduled to receive any nonlive vaccine through 30 days following study intervention with the exception of COVID-19 vaccine administration. Study intervention must be given at least 72 hours following or at least 48 hours prior to any COVID-19 vaccination. Consumes greater than 3 servings of alcoholic beverages per day. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day. Regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A- Moderate RI<br>Single dose of MK-0616 10 mg | Drug: MK-0616<br>* 10 mg capsule administered orally<br>|
| Experimental: Panel B- Healthy Controls<br>Single dose of MK-0616 10 mg | Drug: MK-0616<br>* 10 mg capsule administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of MK-0616 | Blood for plasma samples will be collected at pre-specified timepoints to determine the AUC0-inf of MK-0616 | Pre-dose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours post dose | 
| AUC from Time 0 to Last Measurable Concentration (AUClast) of MK-0616 | Blood for plasma samples will be collected at pre-specified timepoints to determine the AUClast of MK-0616 | Pre-dose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours post dose | 
| Maximum Plasma Concentration (Cmax) of MK-0616 | Blood for plasma samples will be collected at pre-specified time points to determine the Cmax of MK-0616 | Pre-dose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours post dose | 
| Time to Maximum Plasma Concentration (Tmax) of MK-0616 | Blood for plasma samples will be collected at pre-specified time points to determine the Tmax of MK-0616 | Pre-dose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours post dose | 
| Apparent Terminal Half-life (t1/2) of MK-0616 | Blood for plasma samples will be collected at pre-specified time points to determine the t1/2 of MK-0616 | Pre-dose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours post dose | 
| Apparent Clearance (CL/F) of MK-0616 | Blood for plasma samples will be collected at pre-specified time points to determine the CL/F of MK-0616 | Pre-dose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours post dose | 
| Apparent Volume of Distribution (Vz/F) of MK-0616 | Blood for plasma samples will be collected at pre-specified time points to determine the Vz/F of MK-0616 | Pre-dose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention | Up to approximately 14 days | 
| Number of Participants Who Discontinue From the Study due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention | Up to approximately 14 days | 
| Amount Recovered in Urine from 0 to 24 hours (Ae0-24) of MK-0616 | Urine will be collected at pre-specified time points to determine the Ae0-24 of MK-0616 | Pre-dose and and at 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post dose | 
| Fraction of Dose Recovered in Urine (Fe) of MK-0616 | Urine will be collected at pre-specified time points to determine the Fe of MK-0616 | Pre-dose and and at 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post dose | 
| Renal Clearance (CLr) of MK-0616 | Urine will be collected at pre-specified time points to determine the CLr of MK-0616 | Pre-dose and and at 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post dose | 
| Maximum Percent Change in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9) from Baseline | Blood will be collected at pre-specified time points to determine the maximum percent change in free PCSK9 from baseline following administration of a single dose of MK-0616 | Baseline and up to 336 hours post dose |