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Phase 1 N=18 Treatment

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

Moderate Renal Impairment

Enrolled (actual)
18
Serious AEs
0.0%
Results posted
Sep 2024
Primary outcome: Primary: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of MK-0616 — 453; 369 hour*nmol/Liter

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
Enlicitide Chloride (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Merck Sharp & Dohme LLC
Primary completion
May 2023

Outcome Measures

OutcomeResultp-value
PRIMARY
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of MK-0616
453; 369
PRIMARY
Area Under the Concentration- Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of MK-0616.
312; 192
PRIMARY
Maximum Plasma Concentration (Cmax) of MK-0616
5.80; 4.00
PRIMARY
Time to Maximum Plasma Concentration (Tmax) of MK-0616
2.00; 4.66
PRIMARY
Apparent Terminal Half-life (t1/2) of MK-0616
55.1; 48.8
PRIMARY
Apparent Clearance (CL/F) of MK-0616
14.2; 17.5
PRIMARY
Apparent Volume of Distribution (Vz/F) of MK-0616
1130; 1230
SECONDARY
Number of Participants Who Experienced an Adverse Event (AE)
3; 2
SECONDARY
Number of Participants Who Discontinued From the Study Due to an AE
0; 0
SECONDARY
Amount Recovered in Urine From 0 to 24 Hours (Ae0-24) of MK-0616
0.0116; 0.0141
SECONDARY
Fraction of Dose Recovered in Urine (Fe) of MK-0616
0.116; 0.141
SECONDARY
Renal Clearance (CLr) of MK-0616
0.0573; 0.152
SECONDARY
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
-80.5; -66.6; -90.9; -88.6; -90.8; -87.1

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05070390). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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