Clinical trial NCT05934292: Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) Renal Impairment Study (MK-0616-020)
Official title: An Open-Label, Single-Dose Clinical Study to Evaluate the Pharmacokinetics of MK-0616 in Participants With Varying Degrees of Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolaemia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2023-07-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Panel C included participants with ESRD. No urine samples could be obtained on Panel C participants and hence no pharmacokinetic (PK) analysis could be performed for Panel C participants as pre-specified in the protocol.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate
timeFrame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
measure: AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate
timeFrame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
measure: Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate
timeFrame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
measure: Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate
timeFrame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
measure: Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate
timeFrame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
measure: Apparent Clearance (CL/F) of Enlicitide Decanoate
timeFrame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
measure: Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate
timeFrame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Secondary outcomes:
measure: Panel C: Dialysate Clearance (CLd) of Enlicitide Decanoate
timeFrame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
measure: Panel C: Dialysate Concentration (Cd) of Enlicitide Decanoate
timeFrame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
measure: Panel C: Amount of Enlicitide Decanoate Excreted (AEd) in Dialysate
timeFrame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
measure: Panel C: Percentage of Dose (%Dose) of Enlicitide Decanoate Excreted in Dialysate
timeFrame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
measure: Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate
timeFrame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours postdose
measure: Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe)
timeFrame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
measure: Renal Clearance (CLr) of Enlicitide Decanoate
timeFrame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 30 days
measure: Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE
timeFrame: Up to approximately 30 days
measure: Panel C: Number of Participants Who Discontinued From the Study Treatment Due to an AE
timeFrame: Up to approximately 30 days
Other outcomes:
Locations:
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach ( Site 0003)
state: Florida
city: Miami
country: United States
facility: Clinical Pharmacology of Miami ( Site 0005)
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC ( Site 0001)
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center ( Site 0004)
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research, LLC ( Site 0002)
state: Florida
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: