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

NCT05934292 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 0616-020MK-0616-020
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Hypercholesterolaemia

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (10)

• Panel C: Dialysate Clearance (CLd) of Enlicitide Decanoate

  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

  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

  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

  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

  Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours postdose

Study Arms (4)

Panel A: Moderate Renal Impairment (RI)

EXPERIMENTAL

Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1

Drug: Enlicitide Decanoate

Panel B: Severe RI

EXPERIMENTAL

Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1

Drug: Enlicitide Decanoate

Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD)

EXPERIMENTAL

Participants receive Enlicitide Decanoate 20 mg tablet orally on Day 1 and Day 16.

Drug: Enlicitide Decanoate

Panel D: Healthy Controls

EXPERIMENTAL

Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1.

Drug: Enlicitide Decanoate

Interventions

Enlicitide Decanoate DRUG

Oral dose

Also known as: MK-0616

Panel A: Moderate Renal Impairment (RI); Panel B: Severe RI; Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD); Panel D: Healthy Controls

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (5)

Velocity Clinical Research, Hallandale Beach ( Site 0003)

Hallandale, Florida, 33009, United States

Location

Clinical Pharmacology of Miami ( Site 0005)

Miami, Florida, 33014-3616, United States

Location

Advanced Pharma CR, LLC ( Site 0001)

Miami, Florida, 33147, United States

Location

Orlando Clinical Research Center ( Site 0004)

Orlando, Florida, 32809, United States

Location

Genesis Clinical Research, LLC ( Site 0002)

Tampa, Florida, 33603, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

MK-0616

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: July 6, 2023
• Study Start: July 20, 2023
• Primary Completion: January 19, 2024
• Study Completion: January 19, 2024
• Last Updated: February 17, 2025
• Results First Posted: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

US (5)