Clinical trial NCT05070390: A Study of Enlicitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Participants With Moderate Renal Impairment (MK-0616-007)
Official title: An Open-Label Clinical Study to Evaluate the Pharmacokinetics of MK-0616 Following Administration of a Single Dose to Participants With Moderate Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Moderate Renal Impairment
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-10-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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

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 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

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of MK-0616
timeFrame: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose
measure: Area Under the Concentration- Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of MK-0616.
timeFrame: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose
measure: Maximum Plasma Concentration (Cmax) of MK-0616
timeFrame: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose
measure: Time to Maximum Plasma Concentration (Tmax) of MK-0616
timeFrame: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose
measure: Apparent Terminal Half-life (t1/2) of MK-0616
timeFrame: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose
measure: Apparent Clearance (CL/F) of MK-0616
timeFrame: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose
measure: Apparent Volume of Distribution (Vz/F) of MK-0616
timeFrame: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose
Secondary outcomes:
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 14 days
measure: Number of Participants Who Discontinued From the Study Due to an AE
timeFrame: Up to approximately 14 days
measure: Amount Recovered in Urine From 0 to 24 Hours (Ae0-24) of MK-0616
timeFrame: Predose and at 0, 4, 8, 12 and 24 hours postdose
measure: Fraction of Dose Recovered in Urine (Fe) of MK-0616
timeFrame: Predose and at 0, 4, 8, 12, 24, 36 and 48 hours postdose
measure: Renal Clearance (CLr) of MK-0616
timeFrame: Predose and 4, 8, 12, 24, 36, and 48 hours postdose
measure: Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
timeFrame: Baseline (Predose) and up to 336 hours post dose
Other outcomes:
Locations:
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach ( Site 0002)
state: Florida
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC ( Site 0001)
state: Tennessee
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: