A Study of MK-0616 in Participants With Moderate Renal Impairment (MK-0616-007)
- Registration Number
- NCT05070390
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Panel A - Moderate Renal Impairment (RI) Enlicitide Chloride Single dose of enlicitide chloride 10 mg Panel B - Healthy Controls Enlicitide Chloride Single dose of enlicitide chloride 10 mg
- Primary Outcome Measures
Name Time Method Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of MK-0616 Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose 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.
Area Under the Concentration- Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of MK-0616. Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose 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.
Maximum Plasma Concentration (Cmax) of MK-0616 Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose 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.
Time to Maximum Plasma Concentration (Tmax) of MK-0616 Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose 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.
Apparent Terminal Half-life (t1/2) of MK-0616 Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose 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.
Apparent Clearance (CL/F) of MK-0616 Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose 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.
Apparent Volume of Distribution (Vz/F) of MK-0616 Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose 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.
- Secondary Outcome Measures
Name Time Method Number of Participants Who Experienced an Adverse Event (AE) Up to approximately 14 days 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 unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Number of participants who experienced an AE were reported.
Number of Participants Who Discontinued From the Study Due to an AE Up to approximately 14 days 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 unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Number of participants who discontinued from the study due to an AE were reported.
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 Urine samples were collected at pre-specified time points to determine the AE0-24 of MK-0616. Ae0-24 was defined as the amount of MK-0616 recovered in urine from time 0-24 hours.
Fraction of Dose Recovered in Urine (Fe) of MK-0616 Predose and at 0, 4, 8, 12, 24, 36 and 48 hours postdose Urine samples were collected at pre-specified time points to determine the Fe of MK-0616. Fe was defined as the fraction of dose of MK-0616 recovered in urine.
Renal Clearance (CLr) of MK-0616 Predose and 4, 8, 12, 24, 36, and 48 hours postdose Urine samples were collected at pre-specified time points to determine the CLr of MK-0616. was defined as the time it takes for the MK-0616 to be completely removed by the kidneys.
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9) Baseline (Predose) and up to 336 hours post dose Urine samples were collected at pre-specified time points (baseline and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48 and 336 hours postdose) to evaluate the reduction in free PCSK9 from baseline to up to 336 hours postdose after administration of MK-0616. The percent change from baseline in free PCSK9 was reported.
Trial Locations
- Locations (2)
Alliance for Multispecialty Research, LLC ( Site 0001)
🇺🇸Knoxville, Tennessee, United States
Velocity Clinical Research, Hallandale Beach ( Site 0002)
🇺🇸Hallandale Beach, Florida, United States