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

Study Overview
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Brief Summary
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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.

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

Conditions
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End-Stage Renal Disease, Kidney Failure, Chronic

Intervention / Treatment
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* Drug: MK-2060


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-2060<br>MK-2060 administered via intravenous (IV) infusion on days 1, 3, and 5 during the first week and on day 8 during the second week. | Drug: MK-2060<br>* MK-2060 administered via IV infusion<br>|

What is the study measuring?
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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 will 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 |
| --- | --- | --- |
| Area Under the Concentration-Time Curve from 0 to 168 Hours (AUC0-168) of MK-2060 | Blood will be collected at pre-specified time points to determine the AUC of MK-2060 in plasma from 0 to 168 hours. | At protocol specific time points predose and up to 168 hours post-dose | 
| Maximum plasma concentration (Cmax) of MK-2060 | Blood will be collected at pre-specified time points to determine the Cmax of MK-2060 in plasma | At protocol specific time points up to 104 days | 
| Plasma concentration at 168 Hours (C168) of MK-2060 | Blood will be collected 168 hours post-dose to determine the plasma concentration of MK-2060 | 168 hours post-dose | 
| Time to Maximum Plasma Concentration (Tmax) of MK-2060 | Blood will be collected at pre-specified time points to determine the Tmax of MK-2060 in plasma | At protocol specific time points up to 104 days | 
| Terminal Half Life (t1/2) of MK-2060 | Blood will be collected at pre-specified time points to determine the t1/2 of MK-2060 in plasma | At protocol specific time points up to 104 days | 
| Clearance (CL) of MK-2060 | Blood will be collected at pre-specified time points to determine the CL of MK-2060 in plasma | At protocol specific time points up to 104 days | 
| Volume of Distribution (Vz) of MK-2060 | Blood will be collected at pre-specified time points to determine the Vz of MK-2060 in plasma | At protocol specific time points up to 104 days | 
| 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 |