Phase 1
N=33
Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) Renal Impairment Study (MK-0616-020)
Hypercholesterolaemia
Bottom Line
View on ClinicalTrials.gov: NCT05934292 ↗Enrolled (actual)
33
Serious AEs
3.0%
Results posted
Feb 2025
Primary outcome: Primary: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate — 733; 554; 850; 570 hr*nmol/Liter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Enlicitide Decanoate (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Jan 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate |
733; 554; 850; 570; 487 | — |
| PRIMARY AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate |
735; 362; 649; 538; 456 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate |
9.56; 5.8; 8.73; 9.08; 9.72 | — |
| PRIMARY Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate |
16; 2.75; 18.01; 1.00; 1.0 | — |
| PRIMARY Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate |
81.5; 56.4; 53.6; 75.6; 46 | — |
| PRIMARY Apparent Clearance (CL/F) of Enlicitide Decanoate |
17.6; 23.3; 15.2; 22.6; 26.5 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate |
2070; 1890; 1170; 2470; 1760 | — |
| SECONDARY Panel C: Dialysate Clearance (CLd) of Enlicitide Decanoate |
— | — |
| SECONDARY Panel C: Dialysate Concentration (Cd) of Enlicitide Decanoate |
— | — |
| SECONDARY Panel C: Amount of Enlicitide Decanoate Excreted (AEd) in Dialysate |
— | — |
| SECONDARY Panel C: Percentage of Dose (%Dose) of Enlicitide Decanoate Excreted in Dialysate |
— | — |
| SECONDARY Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate |
0.0213; 0.00592; 0.0662 | — |
| SECONDARY Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe) |
0.107; 0.0296; 0.331 | — |
| SECONDARY Renal Clearance (CLr) of Enlicitide Decanoate |
0.0716; 0.0347; 0.243 | — |
| SECONDARY Number of Participants Who Experienced an Adverse Event (AE) |
2; 2; 1; 0 | — |
| SECONDARY Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE |
0; 0; 0 | — |
| SECONDARY Panel C: Number of Participants Who Discontinued From the Study Treatment Due to an AE |
— | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT05934292). 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.