Trial Outcomes & Findings for MK-2060 and Clopidogrel Co-administration Safety and Tolerability Study in Participants With End-Stage Renal Disease (ESRD) (MK-2060-008) (NCT NCT05335005)
NCT ID: NCT05335005
Last Updated: 2024-10-17
Results Overview
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.
COMPLETED
PHASE1
12 participants
Up to approximately 104 days
2024-10-17
Participant Flow
Participant milestones
| Measure |
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.
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|---|---|
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Overall Study
STARTED
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12
|
|
Overall Study
COMPLETED
|
11
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
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.
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|---|---|
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Overall Study
Lost to Follow-up
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1
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Baseline Characteristics
MK-2060 and Clopidogrel Co-administration Safety and Tolerability Study in Participants With End-Stage Renal Disease (ESRD) (MK-2060-008)
Baseline characteristics by cohort
| Measure |
MK-2060
n=12 Participants
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.
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|---|---|
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Age, Continuous
|
57.3 Years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 104 daysPopulation: The analysis population included all participants who received ≥1 dose of MK-2060.
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.
Outcome measures
| Measure |
MK-2060
n=12 Participants
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.
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|---|---|
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Number of Participants Who Experience One or More Bleeding Related Adverse Events (AE)
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0 Participants
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PRIMARY outcome
Timeframe: Up to approximately 104 daysPopulation: The analysis population included all participants who received ≥1 dose of MK-2060.
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.
Outcome measures
| Measure |
MK-2060
n=12 Participants
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.
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|---|---|
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Number of Participants Who Experience One or More AEs
|
6 Participants
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PRIMARY outcome
Timeframe: Up to approximately 8 daysPopulation: The analysis population included all participants who received ≥1 dose of MK-2060.
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.
Outcome measures
| Measure |
MK-2060
n=12 Participants
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.
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|---|---|
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Number of Participants Who Discontinue Study Intervention Due to an AE
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0 Participants
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SECONDARY outcome
Timeframe: Day 1: predose, and 1, 12, 24, and 48 hours postdose. Day 8: predose, and 1, 12, 24, 48, 96, and 168 hours postdose.Population: The analysis population included all participants who received ≥1 dose of MK-2060 and who complied with the protocol sufficiently to ensure that the data are likely to exhibit the effects of treatment according to the underlying scientific model.
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.
Outcome measures
| Measure |
MK-2060
n=12 Participants
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.
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|---|---|
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Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) of MK-2060
Week 1
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2040 hour*nmol/L
Geometric Coefficient of Variation 27.5
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Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) of MK-2060
Week 2
|
9060 hour*nmol/L
Geometric Coefficient of Variation 40.5
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SECONDARY outcome
Timeframe: 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.Population: The analysis population included all participants who received ≥1 dose of MK-2060 and who complied with the protocol sufficiently to ensure that the data are likely to exhibit the effects of treatment according to the underlying scientific model.
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.
Outcome measures
| Measure |
MK-2060
n=12 Participants
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.
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|---|---|
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Maximum Plasma Concentration (Cmax) of MK-2060
Week 1
|
29.7 nmol/L
Geometric Coefficient of Variation 19.9
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Maximum Plasma Concentration (Cmax) of MK-2060
Week 2
|
87.6 nmol/L
Geometric Coefficient of Variation 24.2
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SECONDARY outcome
Timeframe: Days 1 and 8: 168 hours post-dosePopulation: The analysis population included all participants who received ≥1 dose of MK-2060 and who complied with the protocol sufficiently to ensure that the data are likely to exhibit the effects of treatment according to the underlying scientific model.
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.
Outcome measures
| Measure |
MK-2060
n=12 Participants
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.
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|---|---|
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Plasma Concentration at 168 Hours (C168) of MK-2060
Week 1
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43.1 nmol/L
Geometric Coefficient of Variation 26.7
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Plasma Concentration at 168 Hours (C168) of MK-2060
Week 2
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34.3 nmol/L
Geometric Coefficient of Variation 66.2
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SECONDARY outcome
Timeframe: 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.Population: The analysis population included all participants who received ≥1 dose of MK-2060 and who complied with the protocol sufficiently to ensure that the data are likely to exhibit the effects of treatment according to the underlying scientific model.
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.
Outcome measures
| Measure |
MK-2060
n=12 Participants
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.
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|---|---|
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Time to Maximum Plasma Concentration (Tmax) of MK-2060
Week 1
|
1.03 Hours
Interval 0.75 to 1.25
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Time to Maximum Plasma Concentration (Tmax) of MK-2060
Week 2
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1.07 Hours
Interval 0.9 to 12.0
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SECONDARY outcome
Timeframe: Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.Population: The analysis population included all participants who received ≥1 dose of MK-2060 and who complied with the protocol sufficiently to ensure that the data are likely to exhibit the effects of treatment according to the underlying scientific model.
T1/2 was defined as the time required to divide the MK-2060 plasma concentration by two after reaching pseudo-equilibrium.
Outcome measures
| Measure |
MK-2060
n=11 Participants
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.
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|---|---|
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Terminal Half Life (t1/2) of MK-2060
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402 Hours
Geometric Coefficient of Variation 31.5
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SECONDARY outcome
Timeframe: Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.Population: The analysis population included all participants who received ≥1 dose of MK-2060 and who complied with the protocol sufficiently to ensure that the data are likely to exhibit the effects of treatment according to the underlying scientific model.
CLss was defined as the volume of plasma from which MK-2060 was eliminated per unit time following administration, once at steady state.
Outcome measures
| Measure |
MK-2060
n=11 Participants
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.
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|---|---|
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Clearance at Steady State (CLss) of MK-2060
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0.0170 L/hour
Geometric Coefficient of Variation 25.6
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SECONDARY outcome
Timeframe: Day 8: predose, and 1, 12, and 24 hours postdose. Once daily on Days 10, 12, 15, 21, 29, 35, 49, 67, and 104.Population: The analysis population included all participants who received ≥1 dose of MK-2060 and who complied with the protocol sufficiently to ensure that the data are likely to exhibit the effects of treatment according to the underlying scientific model.
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.
Outcome measures
| Measure |
MK-2060
n=11 Participants
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.
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|---|---|
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Apparent Volume of Distribution at Steady State (Vss) of MK-2060
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6.34 Liters
Geometric Coefficient of Variation 33.3
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SECONDARY outcome
Timeframe: Up to approximately 15 daysPopulation: The analysis population included all participants who received ≥1 dose of MK-2060 and who complied with the protocol sufficiently to ensure that the data are likely to exhibit the effects of treatment according to the underlying scientific model.
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.
Outcome measures
| Measure |
MK-2060
n=12 Participants
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.
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|---|---|
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Time to Hemostasis Following MK-2060 Treatment
|
11.0 Minutes
Interval 6.97 to 15.1
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Adverse Events
Run-in (Clopidogrel 75 mg)
MK-2060 25 mg IV/Clopidogrel 75 mg
Serious adverse events
| Measure |
Run-in (Clopidogrel 75 mg)
n=12 participants at risk
Participants continued their established background therapy of daily 75 mg clopidogrel for 2 weeks (days -14 to 0).
|
MK-2060 25 mg IV/Clopidogrel 75 mg
n=12 participants at risk
In addition to standard background therapy of 75 mg clopidogrel, participants received 25 mg MK-2060 intravenous (IV) infusion on days 1, 3, 5, and 8.
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|---|---|---|
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Infections and infestations
Osteomyelitis
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
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Infections and infestations
Pneumonia
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0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Infections and infestations
Staphylococcal sepsis
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site complication
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Nervous system disorders
Syncope
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
Other adverse events
| Measure |
Run-in (Clopidogrel 75 mg)
n=12 participants at risk
Participants continued their established background therapy of daily 75 mg clopidogrel for 2 weeks (days -14 to 0).
|
MK-2060 25 mg IV/Clopidogrel 75 mg
n=12 participants at risk
In addition to standard background therapy of 75 mg clopidogrel, participants received 25 mg MK-2060 intravenous (IV) infusion on days 1, 3, 5, and 8.
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|---|---|---|
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Musculoskeletal and connective tissue disorders
Arthralgia
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Nervous system disorders
Headache
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Nervous system disorders
Metabolic encephalopathy
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Psychiatric disorders
Agitation
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Renal and urinary disorders
Renal hypertension
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 2 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 2 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
|
Vascular disorders
Hypotension
|
0.00%
0/12 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
8.3%
1/12 • Number of events 1 • Run-in (Clopidogrel 75 mg) arm: Approximately 14 days MK-2060 25 mg IV/Clopidogrel 75 mg arm: Up to approximately 108 days
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme LLC
Results disclosure agreements
- Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
- Publication restrictions are in place
Restriction type: OTHER