A Study of Enlicitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Participants With Moderate Renal Impairment (MK-0616-007)

NCT05070390 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 0616-007MK-0616-007
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This study evaluated the safety, tolerability and pharmacokinetic (PK) effects of enlicitide chloride in participants with moderate renal impairment (RI) to those of healthy matched control participants. Moderate RI was defined as the estimated glomerular filtration rate (eGFR) ≥30 and \<60milliliter/minute/1.73meters\^2 (ml/min/1.73m\^2). There is no formal hypothesis.

Conditions

Moderate Renal Impairment

Outcome Measures

Primary Outcomes (7)

• Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of MK-0616

  Blood samples were collected at pre-specified timepoints to determine the AUC0-inf of MK-0616. AUC0-inf was defined as the area under the concentration-time curve of MK-0616 from time zero to infinity.

  Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose

• Area Under the Concentration- Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of MK-0616.

  Blood samples were collected at pre-specified timepoints to determine the AUC0-last of MK-0616. AUC0-last was defined as the area under the concentration-time curve of MK-0616 from time zero to last measurable concentration.

  Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose

• Maximum Plasma Concentration (Cmax) of MK-0616

  Blood samples were collected at pre-specified time points to determine the Cmax of MK-0616. Cmax was defined as the maximum concentration of MK-0616 reached.

  Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose

• Time to Maximum Plasma Concentration (Tmax) of MK-0616

  Blood samples were collected at pre-specified timepoints to determine the Tmax of MK-0616. Tmax was defined as time to the maximum concentration of MK-0616 reached.

  Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose

• Apparent Terminal Half-life (t1/2) of MK-0616

  Blood samples were collected at pre-specified timepoints to determine the t1/2 of MK-0616. t1/2 was defined as the time required to divide the MK-0616 plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-0616.

  Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose

• Apparent Clearance (CL/F) of MK-0616

  Blood samples were collected at pre-specified timepoints to determine the CL/F of MK-0616. CL/F was the apparent total clearance of MK-0616 in plasma over time, assessed as the rate at which MK-0616 was removed from the plasma.

  Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose

• Apparent Volume of Distribution (Vz/F) of MK-0616

  Blood samples were collected at pre-specified timepoints to determine the Vz/F of MK-0616. Vz/F was the apparent volume of distribution of MK-0616 between the plasma and the rest of the body, after dose, assessed as the total volume of MK-0616 that would need to be uniformly distributed to achieve the desired plasma drug concentration.

  Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose

Secondary Outcomes (6)

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 14 days

• Number of Participants Who Discontinued From the Study Due to an AE

  Up to approximately 14 days

• Amount Recovered in Urine From 0 to 24 Hours (Ae0-24) of MK-0616

  Predose and at 0, 4, 8, 12 and 24 hours postdose

• Fraction of Dose Recovered in Urine (Fe) of MK-0616

  Predose and at 0, 4, 8, 12, 24, 36 and 48 hours postdose

• Renal Clearance (CLr) of MK-0616

  Predose and 4, 8, 12, 24, 36, and 48 hours postdose

Study Arms (2)

Panel A - Moderate Renal Impairment (RI)

EXPERIMENTAL

Single dose of enlicitide chloride 10 mg

Drug: Enlicitide Chloride

Panel B - Healthy Controls

EXPERIMENTAL

Single dose of enlicitide chloride 10 mg

Drug: Enlicitide Chloride

Interventions

Enlicitide Chloride DRUG

10 mg capsule administered orally

Also known as: MK-0616

Panel A - Moderate Renal Impairment (RI); Panel B - Healthy Controls

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Renal Impairment (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

You may not qualify if:

• 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 Corona virus disease (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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Velocity Clinical Research, Hallandale Beach ( Site 0002)

Hallandale, Florida, 33009, United States

Location

Alliance for Multispecialty Research, LLC ( Site 0001)

Knoxville, Tennessee, 37920, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

MK-0616

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2021
• First Posted: October 7, 2021
• Study Start: November 16, 2021
• Primary Completion: May 3, 2023
• Study Completion: May 3, 2023
• Last Updated: September 26, 2024
• Results First Posted: September 26, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share

Locations

US (2)