Trial Outcomes & Findings for Study of a Single Intravenous (IV) Dose of MK-3402 in Participants With Impaired Renal Function and in Healthy Controls (MK-3402-004) (NCT NCT04678505)
NCT ID: NCT04678505
Last Updated: 2022-11-04
Results Overview
AUC0-inf is defined as area under the plasma concentration-time curve from dosing to infinity.
TERMINATED
PHASE1
9 participants
Pre-dose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1
2022-11-04
Participant Flow
Male/female participants with mild, moderate, or severe renal impairment (RI), end stage renal disease (ESRD), or healthy matched adults between the ages of 18 and 75 years (inclusive) were recruited at 2 study sites in the United States. However, the study was terminated early due to business reasons prior to enrollment of healthy control participants and participants with severe RI or ESRD, and thus no comparisons could be made.
Participant milestones
| Measure |
Panel A: Mild Renal Impairment
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
Panel C: Severe Renal Impairment
Participants with severe renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
Panel D: Healthy Participants
Healthy matched control participants will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
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Panel E: End-Stage Renal Disease (ESRD) Undergoing Hemodialysis
Participants with ESRD undergoing hemodialysis (HD) will receive a single dose of 100 mg MK-3402 via IV infusion after HD on Day 1 of Period 1 and before HD on Day 1 of Period 2. There will be at least a 6-day washout period before dosing in Period 2.
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|---|---|---|---|---|---|
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Overall Study
STARTED
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4
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5
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0
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0
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0
|
|
Overall Study
COMPLETED
|
4
|
5
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
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0
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0
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0
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0
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of a Single Intravenous (IV) Dose of MK-3402 in Participants With Impaired Renal Function and in Healthy Controls (MK-3402-004)
Baseline characteristics by cohort
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
Total
n=9 Participants
Total of all reporting groups
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|---|---|---|---|
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Age, Continuous
|
60.5 years
STANDARD_DEVIATION 7.0 • n=99 Participants
|
67.6 years
STANDARD_DEVIATION 2.6 • n=107 Participants
|
64.4 years
STANDARD_DEVIATION 6.0 • n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1Population: Participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
AUC0-inf is defined as area under the plasma concentration-time curve from dosing to infinity.
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
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Area Under the Curve From Dosing to Infinity (AUC0-inf) of MK-3402
|
71.9 hr*µmol/L
Geometric Coefficient of Variation 18.2
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96.4 hr*µmol/L
Geometric Coefficient of Variation 17.5
|
PRIMARY outcome
Timeframe: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1Population: Participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
Ceoi is defined as the amount of study drug in plasma following IV infusion administration of study drug. Plasma samples were collected at pre-specified time points and Ceoi was assessed.
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
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Plasma Concentration at the End of Infusion (Ceoi) of MK-3402
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16.8 µmol/L
Geometric Coefficient of Variation 26.0
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14.3 µmol/L
Geometric Coefficient of Variation 31.1
|
PRIMARY outcome
Timeframe: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1Population: Participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
Tmax is defined as the time required for a study drug to reach maximum concentration in plasma. Plasma samples were collected at pre-specified time points and Tmax was assessed.
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
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|---|---|---|
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Time to Maximum Plasma Concentration (Tmax) of MK-3402
|
0.59 hours
Interval 0.53 to 0.62
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0.57 hours
Interval 0.55 to 0.75
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PRIMARY outcome
Timeframe: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1Population: Participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
t½ is defined as the time required for plasma drug concentration of study drug to decrease by 50% from peak.
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
|
Apparent Plasma Half-life (t½) of MK-3402
|
5.06 hours
Geometric Coefficient of Variation 15.2
|
8.12 hours
Geometric Coefficient of Variation 9.1
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PRIMARY outcome
Timeframe: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1Population: Participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
CL is defined as the time it takes for the study drug to be completely removed from the body's plasma.
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
|
Apparent Plasma Clearance (CL) of MK-3402
|
3.13 L/hr
Geometric Coefficient of Variation 18.5
|
2.28 L/hr
Geometric Coefficient of Variation 16.1
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PRIMARY outcome
Timeframe: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1Population: Participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
Vd is defined as the distributed volume of study drug in plasma.
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
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|---|---|---|
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Volume of Distribution (Vd) of MK-3402
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22.9 liters
Geometric Coefficient of Variation 5.3
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26.6 liters
Geometric Coefficient of Variation 20.4
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SECONDARY outcome
Timeframe: Up to 15 daysPopulation: All participants who received ≥1 dose of study drug are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
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Number of Participants With Adverse Events (AE)
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0 Participants
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2 Participants
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SECONDARY outcome
Timeframe: Up to 15 daysPopulation: All participants who received ≥1 dose of study drug are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
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Number of Participants Who Discontinued From Study Due to an AE
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0 Participants
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0 Participants
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SECONDARY outcome
Timeframe: Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusionPopulation: The study was terminated early prior to enrollment of participants on dialysis, and thus no data were collected for this endpoint.
Plasma dialysis samples were to be collected at pre-specified time points to calculate CLDplasma.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusionPopulation: The study was terminated early prior to enrollment of participants on dialysis, and thus no data were collected for this endpoint.
Plasma dialysis samples were to be collected at pre-specified time points to calculate CD.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusionPopulation: The study was terminated early prior to enrollment of participants on dialysis, and thus no data were collected for this endpoint.
Plasma dialysis samples were to be collected at pre-specified time points to calculate AED.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusion.Population: The study was terminated early prior to enrollment of participants on dialysis, and thus no data were collected for this endpoint.
Plasma dialysis samples were to be collected at pre-specified time points to calculate AED (% dose).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusionPopulation: The study was terminated early prior to enrollment of participants on dialysis, and thus no data were collected for this endpoint.
Plasma dialysis samples were to be collected at pre-specified time points to measure CLD dialysate.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdosePopulation: Participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
Ae0-24 is defined as the amount of study drug unchanged in urine after 0-24 hours. Urine samples were collected at pre-specified intervals and Ae0-24 was assessed.
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
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Amount Recovered in Urine From 0 to 24 Hours (Ae0-24) of MK-3402
|
91.8 mg
Geometric Coefficient of Variation 32.7
|
61.5 mg
Geometric Coefficient of Variation 42.4
|
SECONDARY outcome
Timeframe: Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdosePopulation: Participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
Fe is defined as the fraction of the dose of study drug in urine.
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
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Fraction of Dose Recovered in Urine (Fe) of MK-3402
|
86.8 percentage
Geometric Coefficient of Variation 35.1
|
59.7 percentage
Geometric Coefficient of Variation 41.2
|
SECONDARY outcome
Timeframe: Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdosePopulation: Participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included. As the study was terminated early, no participants were enrolled in Panels C, D, or E.
CLr is defined as the time it takes for the study drug to be completely removed by the kidneys.
Outcome measures
| Measure |
Panel A: Mild Renal Impairment
n=4 Participants
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 Participants
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
|
Renal Clearance (CLr) of MK-3402
|
2.81 L/h
Geometric Coefficient of Variation 48.6
|
1.52 L/h
Geometric Coefficient of Variation 36.7
|
Adverse Events
Panel A: Mild Renal Impairment
Panel B: Moderate Renal Impairment
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Panel A: Mild Renal Impairment
n=4 participants at risk
Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.
|
Panel B: Moderate Renal Impairment
n=5 participants at risk
Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.
|
|---|---|---|
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Gastrointestinal disorders
Diarrhoea
|
0.00%
0/4 • Up to 15 days
All participants in Panels A and B who received ≥1 dose of study drug are included. No participants were enrolled into Panels C, D, or E.
|
20.0%
1/5 • Number of events 1 • Up to 15 days
All participants in Panels A and B who received ≥1 dose of study drug are included. No participants were enrolled into Panels C, D, or E.
|
|
Infections and infestations
Vulvovaginal candidiasis
|
0.00%
0/4 • Up to 15 days
All participants in Panels A and B who received ≥1 dose of study drug are included. No participants were enrolled into Panels C, D, or E.
|
20.0%
1/5 • Number of events 1 • Up to 15 days
All participants in Panels A and B who received ≥1 dose of study drug are included. No participants were enrolled into Panels C, D, or E.
|
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Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/4 • Up to 15 days
All participants in Panels A and B who received ≥1 dose of study drug are included. No participants were enrolled into Panels C, D, or E.
|
20.0%
1/5 • Number of events 1 • Up to 15 days
All participants in Panels A and B who received ≥1 dose of study drug are included. No participants were enrolled into Panels C, D, or E.
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/4 • Up to 15 days
All participants in Panels A and B who received ≥1 dose of study drug are included. No participants were enrolled into Panels C, D, or E.
|
20.0%
1/5 • Number of events 3 • Up to 15 days
All participants in Panels A and B who received ≥1 dose of study drug are included. No participants were enrolled into Panels C, D, or E.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
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.
- Publication restrictions are in place
Restriction type: OTHER