MK-2060 and Clopidogrel Co-administration Safety and Tolerability Study in Participants With End-Stage Renal Disease (ESRD) (MK-2060-008)

A Study to Evaluate Safety and Tolerability of Co-administration of MK-2060 and Clopidogrel in Participants With End-Stage Renal Disease on Hemodialysis

MK-2060 is being developed for prevention of thrombotic complications in end-stage renal disease (ESRD). The purpose of this study is to conduct a preliminary evaluation of the safety and tolerability of MK-2060 treatment in combination with a commonly used P2Y12 receptor inhibitor, clopidogrel, in ESRD patients.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic; End-Stage Renal Disease
• Intervention / Treatment: Drug: MK-2060

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center-Clinical Reaserch Unit ( Site 0002)
• Romania
  • Bucuresti
    • București, Bucuresti, Romania, 010701
      • ARENSIA Exploratory Medicine-Clinical Nephrology Hospital "Carol Davila" ( Site 0001)
• United States
  • Florida
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research, LLC ( Site 0003)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has End-Stage Renal Disease (ESRD) maintained on stable outpatient hemodialysis (HD) regimen at a healthcare center for > 3 months prior to dosing.
• On HD regimen at least 3 times per week for a minimum of 3 hours per dialysis session, using a complication-free well-maintained AV fistula or AV graft.
• Is taking clopidogrel for a minimum of 2 weeks prior to the first dosing of MK-2060 administration.
• Has a Body Mass Index (BMI) ≥ 18 and ≤ 45 kg/m^2.

Exclusion Criteria:

• History of cancer (malignancy), including adenocarcinoma, except adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies that have been successfully treated with appropriate follow up.
• Has a history of deep vein thrombosis or pulmonary embolism.
• Has a history of gastrointestinal (GI) bleeding, duodenal polyps or gastric ulcer in the last 5 years or severe hemorrhoidal bleed in last 3 months prior to screening.
• Is positive for hepatitis B surface antigen or human immunodeficiency virus (HIV).
• Has ongoing anticoagulant therapy or antiplatelet therapy, not including clopidogrel. Intradialytic heparin is permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-2060; Participants continued their established background therapy of daily 75 mg clopidogrel for 2 weeks (days -14 to 0). Participants then continued background therapy while receiving 25 mg MK-2060 intravenous (IV) infusion on days 1, 3, 5, and 8.	Drug: MK-2060; MK-2060 administered via IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience One or More Bleeding Related Adverse Events (AE)	Bleeding related AEs include any sign or symptom of bleeding, even if not requiring intervention by a medical/healthcare professional, as well as clinically-relevant non major bleeding or major bleeding.	Up to approximately 104 days
Number of Participants Who Experience One or More AEs	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 104 days
Number of Participants Who Discontinue Study Intervention 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 8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Hemostasis Following MK-2060 Treatment	Time to hemostasis is assessed by measuring the time that pressure is held from removal of dialysis catheters from the dialysis access site [i.e., arteriovenous (AV) fistula or AV graft] until adequate hemostasis has been obtained for both the arterial and venous sites.	Up to approximately 15 days
Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) of MK-2060	The AUC0-168 was defined as the area under the concentration-time curve of MK-2060 in plasma from time zero to 168 hours after administration. The Week 1 value is the extrapolated value using data up to 48 hours postdose Day 1, with the "Partial area" option in WinNonlin software using a Start time of 0 hours and an End time of 168 hours. Week 2 value included data for Day 8: predose, and 1, 12, 24, 48, 96, and 168 hours postdose.	Day 1: predose, and 1, 12, 24, and 48 hours postdose. Day 8: predose, and 1, 12, 24, 48, 96, and 168 hours postdose.
Maximum Plasma Concentration (Cmax) of MK-2060	Cmax was defined as the maximum concentration of MK-2060 observed in plasma after administration. Week 2 value included data for Day 8: predose and 1, 12, 24, 48, 96, and 168 hours postdose.	Day 1: predose, and 1, 12, and 48 hours postdose. Day 8: predose, and 1, 12, and 24 hours postdose; and once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.
Plasma Concentration at 168 Hours (C168) of MK-2060	C168 was defined as the concentration of MK-2060 observed in plasma 168 hours after administration. Week 2 value included data for Day 8: 168 hours postdose.	Days 1 and 8: 168 hours post-dose
Time to Maximum Plasma Concentration (Tmax) of MK-2060	Tmax was defined as the time required to reach the maximum concentration of MK-2060 observed in plasma after administration. Week 2 value included data for Day 8: predose and 1, 12, 24, 48, 96, and 168 hours postdose.	Day 1: predose, and 1, 12, and 48 hours postdose. Day 8: predose, and 1, 12, and 24 hours postdose; and once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.
Terminal Half Life (t1/2) of MK-2060	T1/2 was defined as the time required to divide the MK-2060 plasma concentration by two after reaching pseudo-equilibrium.	Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.
Clearance at Steady State (CLss) of MK-2060	CLss was defined as the volume of plasma from which MK-2060 was eliminated per unit time following administration, once at steady state.	Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.
Apparent Volume of Distribution at Steady State (Vss) of MK-2060	Vss was defined as the volume of plasma that would be necessary to contain the total amount of administered MK-2060 at the same concentration that MK-2060 was observed in the blood plasma after reaching steady state.	Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2022
• Primary Completion (Actual): February 14, 2023
• Study Completion (Actual): February 14, 2023

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: 2060-008; MK-2060-008 (Other Identifier: Merck); 2021-005333-17 (EudraCT Number)

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