MK-0616 (Oral PCSK9 Inhibitor) Renal Impairment Study 2 (MK-0616-020)

An Open-Label, Single-Dose Clinical Study to Evaluate the Pharmacokinetics of MK-0616 in Participants With Varying Degrees of Renal Impairment

The primary objective of the study is to compare the plasma pharmacokinetics (PK) of MK-0616 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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolaemia
• Intervention / Treatment: Drug: MK-0616

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• United States
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach ( Site 0003)
    • Miami, Florida, United States, 33014-3616
      • Clinical Pharmacology of Miami ( Site 0005)
    • Miami, Florida, United States, 33147
      • Advanced Pharma CR, LLC ( Site 0001)
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center ( Site 0004)
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research, LLC ( Site 0002)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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/m2 and ≤ 40 kg/m2, 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: Moderate Renal Impairment (RI); Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days)	Drug: MK-0616; Single oral dose
Experimental: Panel B: Severe RI; Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days)	Drug: MK-0616; Single oral dose
Experimental: Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD); Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days). Period 2 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 2 = 15 days). A washout period of 14 days will separate Period 1 and Period 2.	Drug: MK-0616; Single oral dose
Experimental: Panel D: Healthy; Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days)	Drug: MK-0616; Single oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Panels A, B, and D: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of MK-0616: Period 1	Blood for plasma samples will be collected at pre-specified timepoints to determine the AUC0-inf of MK-0616	Period 1: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose (Period 1 = 15 days)
Panel C: AUC0-inf of MK-0616: Periods 1 and 2	Blood for plasma samples will be collected at pre-specified timepoints to determine the AUC0-inf of MK-0616	Periods 1 and 2: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose (each period = 15 days)
Panels A, B and D: AUC from Time 0 to Last Measurable Concentration (AUClast) of MK-0616: Period 1	Blood for plasma samples will be collected at pre-specified timepoints to determine the AUClast of MK-0616	Period 1: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose (Period 1 = 15 days)
Panel C: AUClast of MK-0616: Periods 1 and 2	Blood for plasma samples will be collected at pre-specified timepoints to determine the AUClast of MK-0616	Periods 1 and 2: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose (each period = 15 days
Panels A, B and D: Maximum Plasma Concentration (Cmax) of MK-0616: Period 1	Blood for plasma samples will be collected at pre-specified time points to determine the Cmax of MK-0616	Period 1: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 postdose (Period 1 = 15 days)
Panel C: Maximum Plasma Concentration (Cmax) of MK-0616: Periods 1 and 2	Blood for plasma samples will be collected at pre-specified time points to determine the Cmax of MK-0616	Periods 1 and 2: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose (each period = 15 days
Panel A, B, and D: Time to Maximum Plasma Concentration (Tmax) of MK-0616: Period 1	Blood for plasma samples will be collected at pre-specified time points to determine the Tmax of MK-0616	Period 1: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose
Panel C: Time to Maximum Plasma Concentration (Tmax) of MK-0616: Periods 1 and 2	Blood for plasma samples will be collected at pre-specified time points to determine the Tmax of MK-0616	Periods 1 and 2: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose
Panels A, B and D: Apparent Terminal Half-life (t1/2) of MK-0616: Period 1	Blood for plasma samples will be collected at pre-specified time points to determine the t1/2 of MK-0616	Period 1: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose
Panel C: t1/2 of MK-0616: Periods 1 and 2	Blood for plasma samples will be collected at pre-specified time points to determine the t1/2 of MK-0616	Periods 1 and 2: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose
Panel A, B and D: Apparent Clearance (CL/F) of MK-0616: Period 1	Blood for plasma samples will be collected at pre-specified time points to determine the CL/F of MK-0616	Period 1: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose (Period 1 = 15 days)
Panel C: Apparent Clearance (CL/F) of MK-0616: Periods 1 and 2	Blood for plasma samples will be collected at pre-specified time points to determine the CL/F of MK-0616	Periods 1 and 2: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose
Panels A, B and D: Apparent Volume of Distribution (Vz/F) of MK-0616	Blood for plasma samples will be collected at pre-specified time points to determine the Vz/F of MK-0616	Period 1: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose
Panel C: Apparent Volume of Distribution (Vz/F) of MK-0616	Blood for plasma samples will be collected at pre-specified time points to determine the Vz/F of MK-0616	Periods 1 and 2: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dialysate Clearance (CLd) of MK-0616	CLd is the amount of MK-0616 cleared from plasma via dialysis.	Predose and up to 8 hours postdose- Panel C (Period 2)
Dialysate Concentration of MK-0616	Cd is the concentration of MK-0616 in dialysate.	Predose and up to 8 hours postdose- Panel C (Period 2)
Amount of MK-0616 Excreted (AEd) in Dialysate	The amount of MK-0616 excreted in the dialysate will be assessed.	Predose and up to 8 hours postdose- Panel C (Period 2)
Percentage of Dose (%Dose) of MK-0616 Excreted in Dialysate	The percentage of the dose of MK-0616 in the dialysate will be assessed.	Predose and up to 8 hours postdose- Panel C (Period 2)
Amount of MK-0616 Excreted in Urine from 0 to 24 hours (AE0-24)	The amount of MK-0616 excreted in urine in first 24 hours after dosing will be reported.	Predose and up to 24 hours postdose (All Panels: Period 1; Panel C: Period 2)
Fraction of Unchanged MK-0616 Excreted in Urine (Fe)	The fraction of unchanged MK-0616 excreted in urine will be reported	Predose and up to 24 hours postdose (All Panels: Period 1; Panel C: Period 2)
Renal Clearance (CLr) of MK-0616	The CLr of MK-0616 will be reported	Predose and up to 24 hours postdose (All Panels: Period 1; Panel C: Period 2)
Percentage of Participants Who Experience at Least 1 Adverse Event (AE)	An AE is 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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention	Up to approximately 30 days
Percentage of Participants Who Discontinue From the Study due to an AE	An AE is 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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention	Up to approximately 30 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Actual): January 19, 2024
• Study Completion (Actual): January 19, 2024

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: 0616-020; MK-0616-020 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No