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

Primary Purpose

Hypercholesterolaemia

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MK-0616
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypercholesterolaemia

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Velocity Clinical Research, Hallandale Beach ( Site 0003)Recruiting
  • Clinical Pharmacology of Miami ( Site 0005)Recruiting
  • Advanced Pharma CR, LLC ( Site 0001)Recruiting
  • Orlando Clinical Research Center ( Site 0004)Recruiting
  • Genesis Clinical Research, LLC ( Site 0002)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Panel A: Moderate Renal Impairment (RI)

Panel B: Severe RI

Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD)

Panel D: Healthy

Arm Description

Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days)

Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days)

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.

Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days)

Outcomes

Primary Outcome Measures

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
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
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
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
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
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
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
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
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
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
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
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
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
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

Secondary Outcome Measures

Dialysate Clearance (CLd) of MK-0616
CLd is the amount of MK-0616 cleared from plasma via dialysis.
Dialysate Concentration of MK-0616
Cd is the concentration of MK-0616 in dialysate.
Amount of MK-0616 Excreted (AEd) in Dialysate
The amount of MK-0616 excreted in the dialysate will be assessed.
Percentage of Dose (%Dose) of MK-0616 Excreted in Dialysate
The percentage of the dose of MK-0616 in the dialysate will be assessed.
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.
Fraction of Unchanged MK-0616 Excreted in Urine (Fe)
The fraction of unchanged MK-0616 excreted in urine will be reported
Renal Clearance (CLr) of MK-0616
The CLr of MK-0616 will be reported
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
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

Full Information

First Posted
June 5, 2023
Last Updated
August 28, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05934292
Brief Title
MK-0616 (Oral PCSK9 Inhibitor) Renal Impairment Study 2 (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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 20, 2023 (Actual)
Primary Completion Date
June 24, 2024 (Anticipated)
Study Completion Date
June 24, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolaemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Panel A: Moderate Renal Impairment (RI)
Arm Type
Experimental
Arm Description
Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days)
Arm Title
Panel B: Severe RI
Arm Type
Experimental
Arm Description
Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days)
Arm Title
Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD)
Arm Type
Experimental
Arm Description
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.
Arm Title
Panel D: Healthy
Arm Type
Experimental
Arm Description
Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days)
Intervention Type
Drug
Intervention Name(s)
MK-0616
Intervention Description
Single oral dose
Primary Outcome Measure Information:
Title
Panels A, B, and D: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of MK-0616: Period 1
Description
Blood for plasma samples will be collected at pre-specified timepoints to determine the AUC0-inf of MK-0616
Time Frame
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)
Title
Panel C: AUC0-inf of MK-0616: Periods 1 and 2
Description
Blood for plasma samples will be collected at pre-specified timepoints to determine the AUC0-inf of MK-0616
Time Frame
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)
Title
Panels A, B and D: AUC from Time 0 to Last Measurable Concentration (AUClast) of MK-0616: Period 1
Description
Blood for plasma samples will be collected at pre-specified timepoints to determine the AUClast of MK-0616
Time Frame
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)
Title
Panel C: AUClast of MK-0616: Periods 1 and 2
Description
Blood for plasma samples will be collected at pre-specified timepoints to determine the AUClast of MK-0616
Time Frame
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
Title
Panels A, B and D: Maximum Plasma Concentration (Cmax) of MK-0616: Period 1
Description
Blood for plasma samples will be collected at pre-specified time points to determine the Cmax of MK-0616
Time Frame
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)
Title
Panel C: Maximum Plasma Concentration (Cmax) of MK-0616: Periods 1 and 2
Description
Blood for plasma samples will be collected at pre-specified time points to determine the Cmax of MK-0616
Time Frame
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
Title
Panel A, B, and D: Time to Maximum Plasma Concentration (Tmax) of MK-0616: Period 1
Description
Blood for plasma samples will be collected at pre-specified time points to determine the Tmax of MK-0616
Time Frame
Period 1: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose
Title
Panel C: Time to Maximum Plasma Concentration (Tmax) of MK-0616: Periods 1 and 2
Description
Blood for plasma samples will be collected at pre-specified time points to determine the Tmax of MK-0616
Time Frame
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
Title
Panels A, B and D: Apparent Terminal Half-life (t1/2) of MK-0616: Period 1
Description
Blood for plasma samples will be collected at pre-specified time points to determine the t1/2 of MK-0616
Time Frame
Period 1: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose
Title
Panel C: t1/2 of MK-0616: Periods 1 and 2
Description
Blood for plasma samples will be collected at pre-specified time points to determine the t1/2 of MK-0616
Time Frame
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
Title
Panel A, B and D: Apparent Clearance (CL/F) of MK-0616: Period 1
Description
Blood for plasma samples will be collected at pre-specified time points to determine the CL/F of MK-0616
Time Frame
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)
Title
Panel C: Apparent Clearance (CL/F) of MK-0616: Periods 1 and 2
Description
Blood for plasma samples will be collected at pre-specified time points to determine the CL/F of MK-0616
Time Frame
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
Title
Panels A, B and D: Apparent Volume of Distribution (Vz/F) of MK-0616
Description
Blood for plasma samples will be collected at pre-specified time points to determine the Vz/F of MK-0616
Time Frame
Period 1: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose
Title
Panel C: Apparent Volume of Distribution (Vz/F) of MK-0616
Description
Blood for plasma samples will be collected at pre-specified time points to determine the Vz/F of MK-0616
Time Frame
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 Measure Information:
Title
Dialysate Clearance (CLd) of MK-0616
Description
CLd is the amount of MK-0616 cleared from plasma via dialysis.
Time Frame
Predose and up to 8 hours postdose- Panel C (Period 2)
Title
Dialysate Concentration of MK-0616
Description
Cd is the concentration of MK-0616 in dialysate.
Time Frame
Predose and up to 8 hours postdose- Panel C (Period 2)
Title
Amount of MK-0616 Excreted (AEd) in Dialysate
Description
The amount of MK-0616 excreted in the dialysate will be assessed.
Time Frame
Predose and up to 8 hours postdose- Panel C (Period 2)
Title
Percentage of Dose (%Dose) of MK-0616 Excreted in Dialysate
Description
The percentage of the dose of MK-0616 in the dialysate will be assessed.
Time Frame
Predose and up to 8 hours postdose- Panel C (Period 2)
Title
Amount of MK-0616 Excreted in Urine from 0 to 24 hours (AE0-24)
Description
The amount of MK-0616 excreted in urine in first 24 hours after dosing will be reported.
Time Frame
Predose and up to 24 hours postdose (All Panels: Period 1; Panel C: Period 2)
Title
Fraction of Unchanged MK-0616 Excreted in Urine (Fe)
Description
The fraction of unchanged MK-0616 excreted in urine will be reported
Time Frame
Predose and up to 24 hours postdose (All Panels: Period 1; Panel C: Period 2)
Title
Renal Clearance (CLr) of MK-0616
Description
The CLr of MK-0616 will be reported
Time Frame
Predose and up to 24 hours postdose (All Panels: Period 1; Panel C: Period 2)
Title
Percentage of Participants Who Experience at Least 1 Adverse Event (AE)
Description
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
Time Frame
Up to approximately 30 days
Title
Percentage of Participants Who Discontinue From the Study due to an AE
Description
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
Time Frame
Up to approximately 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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/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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toll Free Number
Phone
1-888-577-8839
Email
Trialsites@merck.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Velocity Clinical Research, Hallandale Beach ( Site 0003)
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
954-455-5757
Facility Name
Clinical Pharmacology of Miami ( Site 0005)
City
Miami
State/Province
Florida
ZIP/Postal Code
33014-3616
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
305-817-2900
Facility Name
Advanced Pharma CR, LLC ( Site 0001)
City
Miami
State/Province
Florida
ZIP/Postal Code
33147
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
786-863-3320
Facility Name
Orlando Clinical Research Center ( Site 0004)
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
407-257-3462
Facility Name
Genesis Clinical Research, LLC ( Site 0002)
City
Tampa
State/Province
Florida
ZIP/Postal Code
33603
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
813-755-4403

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information

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

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