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

Conditions

End-Stage Renal Disease, Kidney Failure, Chronic

Brief summary

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.

Related papers

No related papers found yet.

Interventions

DRUGMK-2060

MK-2060 administered via IV infusion

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Who Experience One or More Bleeding Related Adverse Events (AE)	Up to approximately 104 days	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.
Number of Participants Who Experience One or More AEs	Up to approximately 104 days	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.
Number of Participants Who Discontinue Study Intervention Due to an AE	Up to approximately 8 days	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.

Secondary

Measure	Time frame	Description
Time to Maximum Plasma Concentration (Tmax) of MK-2060	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.	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.
Terminal Half Life (t1/2) of MK-2060	Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.	T1/2 was defined as the time required to divide the MK-2060 plasma concentration by two after reaching pseudo-equilibrium.
Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) of MK-2060	Day 1: predose, and 1, 12, 24, and 48 hours postdose. Day 8: predose, and 1, 12, 24, 48, 96, and 168 hours postdose.	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.
Apparent Volume of Distribution at Steady State (Vss) of MK-2060	Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.	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.
Time to Hemostasis Following MK-2060 Treatment	Up to approximately 15 days	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.
Clearance at Steady State (CLss) of MK-2060	Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.	CLss was defined as the volume of plasma from which MK-2060 was eliminated per unit time following administration, once at steady state.
Maximum Plasma Concentration (Cmax) of MK-2060	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.	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.
Plasma Concentration at 168 Hours (C168) of MK-2060	Days 1 and 8: 168 hours post-dose	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.

Countries

Israel, Romania, United States

Participant flow

Participants by arm

Arm	Count
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.	12
Total	12

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	1

Baseline characteristics

Characteristic	MK-2060
Age, Continuous	57.3 Years STANDARD_DEVIATION 8.2
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	7 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	5 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	12 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 12
other Total, other adverse events	1 / 12	5 / 12
serious Total, serious adverse events	0 / 12	3 / 12

Outcome results

Primary

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.

Time frame: Up to approximately 8 days

Population: The analysis population included all participants who received ≥1 dose of MK-2060.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
MK-2060	Number of Participants Who Discontinue Study Intervention Due to an AE	0 Participants

Primary

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.

Time frame: Up to approximately 104 days

Population: The analysis population included all participants who received ≥1 dose of MK-2060.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
MK-2060	Number of Participants Who Experience One or More AEs	6 Participants

Primary

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.

Time frame: Up to approximately 104 days

Population: The analysis population included all participants who received ≥1 dose of MK-2060.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
MK-2060	Number of Participants Who Experience One or More Bleeding Related Adverse Events (AE)	0 Participants

Secondary

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.

Time frame: Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.