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

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

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.

Study Overview

• Status: Completed
• Conditions: Moderate Renal Impairment
• Intervention / Treatment: Drug: MK-0616

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach ( Site 0002)
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research, LLC ( Site 0001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2021
• Primary Completion (Actual): May 3, 2023
• Study Completion (Actual): May 3, 2023

Study Registration Dates

• First Submitted: October 1, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 7, 2021

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency
• Other Study ID Numbers: 0616-007; MK-0616-007 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No