Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) Renal Impairment Study (MK-0616-020)

An Open-Label, Single-Dose Clinical Study to Evaluate the Pharmacokinetics of MK-0616 in Participants With Varying Degrees of Renal Impairment

The primary objective of the study is to compare the plasma pharmacokinetics (PK) of enlicitide decanoate following a single 20 mg dose in participants on a background of statin therapy with varying degrees of renal impairment (moderate, severe, end stage renal disease [ESRD]) to those of healthy mean matched control participants on a background of statin therapy. There is no formal hypothesis.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolaemia
• Intervention / Treatment: Drug: Enlicitide Decanoate

Detailed Description

Panel C included participants with ESRD. No urine samples could be obtained on Panel C participants and hence no pharmacokinetic (PK) analysis could be performed for Panel C participants as pre-specified in the protocol.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach ( Site 0003)
    • Miami, Florida, United States, 33014-3616
      • Clinical Pharmacology of Miami ( Site 0005)
    • Miami, Florida, United States, 33147
      • Advanced Pharma CR, LLC ( Site 0001)
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center ( Site 0004)
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research, LLC ( Site 0002)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Be in good health with the exception of renal impairment (RI) and hypercholesterolemia for participants in Panels A, B, and C. Participants with RI that have stable, chronic medical or psychiatric conditions, including but not limited to hypertension, hypercholesterolemia, diabetes mellitus, hyper- or hypothyroidism, gout, and chronic anxiety or depression may be included at the discretion of the investigator
• Body Mass Index (BMI) ≥ 18 kg/m^2 and ≤ 40 kg/m^2, inclusive
• Be on a stable dose of any statin therapy defined as: no changes to dose or type of statin therapy for at least 2 months prior to Screening and participant anticipates no changes to statin therapy throughout the study until the poststudy visit

Exclusion Criteria:

• History or presence of renal artery stenosis
• Had a functioning renal transplant in the past 5 years and is taking transplant medication
• Participants in panels A, B and D: Has rapidly fluctuating renal function as determined by historical measurements
• Has a history gastrointestinal disease which might affect food and drug absorption, as determined by the investigator, or has had gastric bypass or similar surgery
• History of cancer (malignancy)
• History of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
• Has received an anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) small molecule treatment, monoclonal antibody, or short interfering RNA (siRNA) or RNA interference (ie, Inclisiran) within 12 months prior to Screening
• Participants with RI (Panels A, B, and C): Taking medications to treat chronic medical conditions and/or conditions associated with renal disease, if participant has not been on a stable regimen for at least 1 month (other than statins, which require a stable dose for at least 2 months) prior to administration of the initial dose of study intervention, and/or is unable to withhold the use of the medication(s) within 4 hours prior to and 4 hours after administration of study intervention
• Participated in another investigational study within 4 weeks prior to the prestudy (screening) visit
• Consumes greater than 3 servings of alcoholic beverages per day
• Consumes excessive amounts, defined as greater than 6 servings of caffeinated beverages per day

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: Moderate Renal Impairment (RI); Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1	Drug: Enlicitide Decanoate; Oral dose; Other Names: MK-0616
Experimental: Panel B: Severe RI; Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1	Drug: Enlicitide Decanoate; Oral dose; Other Names: MK-0616
Experimental: Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD); Participants receive Enlicitide Decanoate 20 mg tablet orally on Day 1 and Day 16.	Drug: Enlicitide Decanoate; Oral dose; Other Names: MK-0616
Experimental: Panel D: Healthy Controls; Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1.	Drug: Enlicitide Decanoate; Oral dose; Other Names: MK-0616

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 Enlicitide Decanoate	AUC0-inf was a measure of the total amount of drug in the plasma from the dose administration extrapolated to infinity. Blood for plasma samples was collected at pre-specified timepoints to determine the AUC0-inf of enlicitide decanoate for Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C ESRD - enlicitide decanoate pre-hemodialysis and Panel C ESRD - enlicitide decanoate post-hemodialysis to report AUC0-inf. Per protocol, mean AUC0-inf was reported.	Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate	AUClast was defined as the area under the concentration-time curve of enlicitide decanoate from time zero to last measurable concentration. Blood for plasma samples was collected at pre-specified timepoints to determine the AUClast of enlicitide decanoate in Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C ESRD - enlicitide decanoate pre-hemodialysis and Panel C ESRD - enlicitide decanoate post-hemodialysis to report AUClast. Per protocol, mean AUClast was reported.	Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate	Cmax was defined as the maximum or peak concentration of enlicitide decanoate observed after its administration. Blood for plasma samples was collected at pre-specified time points to determine the Cmax of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Cmax. Per protocol, mean Cmax was reported.	Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate	Tmax was defined as the time required for a study drug to reach maximum concentration in plasma. Blood for plasma samples was collected at pre-specified time points to determine the Tmax of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Tmax. Per protocol, mean Tmax was reported.	Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate	Half-life (t1/2) was defined as the time required for plasma drug concentration of enclitide decanoate to decrease by 50% from peak. Blood for plasma samples was collected at pre-specified time points to determine the t1/2 of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report t1/2. Per protocol, mean t1/2 was reported.	Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Apparent Clearance (CL/F) of Enlicitide Decanoate	CL/F was the apparent total clearance of enlicitide decanoate in plasma over time. Blood for plasma samples was collected at pre-specified timepoints to determine the CL/F of enlicitide decanoate for Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report CL/F. Per protocol, mean CL/F was reported.	Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate	Vz/F was the apparent volume of distribution of enlicitide decanoate between the plasma and the rest of the body, after dose, assessed as the total volume of enlicitide decanoate that would need to be uniformly distributed to achieve the desired plasma drug concentration. Blood for plasma samples was collected at pre-specified time points to determine the Vz/F of Enlicitide Decanoate in Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Vz/F. Per protocol, mean Vz/F was reported.	Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Panel C: Dialysate Clearance (CLd) of Enlicitide Decanoate	CLd was the measure of the amount of enlicitide decanoate cleared from plasma via dialysis. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine mean CLd.	Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Panel C: Dialysate Concentration (Cd) of Enlicitide Decanoate	Cd was the measure of the concentration of enlicitide decanoate in dialysate. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine mean Cd.	Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Panel C: Amount of Enlicitide Decanoate Excreted (AEd) in Dialysate	AEd was the measure of the amount of enlicitide decanoate excreted in the dialysate. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine mean AEd.	Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Panel C: Percentage of Dose (%Dose) of Enlicitide Decanoate Excreted in Dialysate	%Dose was the percentage of the dose of enlicitide decanoate excreted in the dialysate. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine %Dose.	Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate	AE0-24 was the measure of the amount of enlicitide decanoate excreted at 0 to 24 hours. Urine samples were to be collected to determine the AE0-24 after administration of enlicitide decanoate for Panels A, B, C, and D. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report AE0-24. Per protocol, mean AE0-24 was reported.	Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours postdose
Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe)	Fe was the measure of the percentage of unchanged enlicitide decanoate excreted in the urine. The percentage of enlicitide decanoate that was excreted unchanged in urine over the 24-hr collection interval (Fe) was calculated as 100 times the ratio of Ae0-24 and dose. Urine samples were to be collected to determine the Fe after administration of enlicitide decanoate for Panels A, B, C, and D. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Fe.	Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Renal Clearance (CLr) of Enlicitide Decanoate	CLr was the measure of how quickly enlicitide decanoate was removed from the plasma by the kidney and excreted in urine. Urine samples were to be collected to determine the CLr after administration of enlicitide decanoate for Panels A, B, C, and D. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report CLr. Per protocol, mean CLr was reported.	Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Number of Participants Who Experienced an Adverse Event (AE)	An AE was 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. The number of participants who experienced an AE were reported.	Up to approximately 30 days
Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE	An AE was 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. The number of Panel A, B, and D participants who discontinued study treatment due to an AE were reported.	Up to approximately 30 days
Panel C: Number of Participants Who Discontinued From the Study Treatment Due to an AE	An AE was 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. The number of Panel C participants who discontinued study treatment due to an AE were reported.	Up to approximately 30 days

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Actual): January 19, 2024
• Study Completion (Actual): January 19, 2024

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Hypercholesterolemia
• Other Study ID Numbers: 0616-020; MK-0616-020 (Other Identifier: MSD)

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