Trial Outcomes & Findings for Islatravir and Methadone Pharmacokinetics (MK-8591-029) (NCT NCT04568603)
NCT ID: NCT04568603
Last Updated: 2025-01-28
Results Overview
The AUC0-24 of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
COMPLETED
PHASE1
14 participants
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
2025-01-28
Participant Flow
Methadone-maintained participants were recruited at 2 study sites in the United States.
Participant milestones
| Measure |
Methadone + ISL
Methadone-maintained participants (20 to 200 mg \[locally-provided\] once daily \[QD\] from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with islatravir (ISL) 60 mg.
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|---|---|
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Overall Study
STARTED
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14
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Overall Study
Received ISL on Day 2
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13
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Overall Study
COMPLETED
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13
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
Methadone + ISL
Methadone-maintained participants (20 to 200 mg \[locally-provided\] once daily \[QD\] from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with islatravir (ISL) 60 mg.
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Overall Study
Physician Decision
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1
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Baseline Characteristics
Islatravir and Methadone Pharmacokinetics (MK-8591-029)
Baseline characteristics by cohort
| Measure |
Methadone + ISL
n=14 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Age, Continuous
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43.5 Years
STANDARD_DEVIATION 12.0 • n=5 Participants
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Sex: Female, Male
Female
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5 Participants
n=5 Participants
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Sex: Female, Male
Male
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9 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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3 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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11 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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1 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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Race (NIH/OMB)
White
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12 Participants
n=5 Participants
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|
Race (NIH/OMB)
More than one race
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1 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The AUC0-24 of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone
Day 1: Methadone Alone
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61.9 ng*h/mL/mg
Interval 49.3 to 77.7
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Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone
Day 2: Methadone + ISL
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63.9 ng*h/mL/mg
Interval 52.2 to 78.1
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PRIMARY outcome
Timeframe: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The AUC0-24hr of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Dose-Normalized AUC0-24 of S-Methadone
Day 1: Methadone Alone
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63.1 ng*h/mL/mg
Interval 48.9 to 81.5
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Dose-Normalized AUC0-24 of S-Methadone
Day 2: Methadone + ISL
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65.1 ng*h/mL/mg
Interval 51.7 to 82.0
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SECONDARY outcome
Timeframe: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The Cmax of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Dose-Normalized Maximum Plasma Concentration (Cmax) of R-Methadone
Day 1: Methadone Alone
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3.64 ng/mL/mg
Interval 3.0 to 4.43
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Dose-Normalized Maximum Plasma Concentration (Cmax) of R-Methadone
Day 2: Methadone + ISL
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3.71 ng/mL/mg
Interval 3.14 to 4.4
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SECONDARY outcome
Timeframe: Days 1 and 2: 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The C24 of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Dose-Normalized Plasma Concentration 24 Hours Postdose (C24) of R-Methadone
Day 1: Methadone Alone
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2.09 ng/ml/mg
Interval 1.63 to 2.69
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Dose-Normalized Plasma Concentration 24 Hours Postdose (C24) of R-Methadone
Day 2: Methadone + ISL
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2.23 ng/ml/mg
Interval 1.78 to 2.78
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SECONDARY outcome
Timeframe: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The Tmax of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Time to Maximum Plasma Concentration (Tmax) of R-Methadone
Day 1: Methadone Alone
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2.00 hours
Interval 1.47 to 3.0
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Time to Maximum Plasma Concentration (Tmax) of R-Methadone
Day 2: Methadone + ISL
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2.00 hours
Interval 0.67 to 4.0
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SECONDARY outcome
Timeframe: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The Cmax of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Dose-Normalized Cmax of S-Methadone
Day 1: Methadone Alone
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4.25 ng/mL/mg
Interval 3.45 to 5.25
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Dose-Normalized Cmax of S-Methadone
Day 2: Methadone + ISL
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4.31 ng/mL/mg
Interval 3.49 to 5.32
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SECONDARY outcome
Timeframe: Days 1 and 2: 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The C24 of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Dose-Normalized C24 of S-Methadone
Day 1: Methadone Alone
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1.91 ng/ml/mg
Interval 1.44 to 2.54
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Dose-Normalized C24 of S-Methadone
Day 2: Methadone + ISL
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2.07 ng/ml/mg
Interval 1.6 to 2.68
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SECONDARY outcome
Timeframe: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The Tmax of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Tmax of S-Methadone
Day 1: Methadone Alone
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1.50 hours
Interval 1.02 to 3.0
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Tmax of S-Methadone
Day 2:Methadone + ISL
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2.00 hours
Interval 0.67 to 3.0
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SECONDARY outcome
Timeframe: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The AUC0-24hr of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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|---|---|
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Dose-Normalized AUC0-24 of Total Methadone
Day 1: Methadone Alone
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126 ng*h/mL/mg
Interval 99.1 to 159.0
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Dose-Normalized AUC0-24 of Total Methadone
Day 2: Methadone + ISL
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129 ng*h/mL/mg
Interval 105.0 to 160.0
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SECONDARY outcome
Timeframe: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The Cmax of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Dose-Normalized Cmax of Total Methadone
Day 1: Methadone Alone
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7.91 ng/mL/mg
Interval 6.48 to 9.66
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Dose-Normalized Cmax of Total Methadone
Day 2: Methadone + ISL
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8.02 ng/mL/mg
Interval 6.64 to 9.68
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SECONDARY outcome
Timeframe: Days 1 and 2: 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The C24 of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Dose-Normalized C24 of Total Methadone
Day 1: Methadone Alone
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4.03 ng/ml/mg
Interval 3.1 to 5.23
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Dose-Normalized C24 of Total Methadone
Day 2: Methadone + ISL
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4.32 ng/ml/mg
Interval 3.42 to 5.45
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SECONDARY outcome
Timeframe: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdosePopulation: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
The Tmax of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Tmax of Total Methadone
Day 1: Methadone Alone
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2.00 hours
Interval 1.47 to 3.0
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Tmax of Total Methadone
Day 2: Methadone + ISL
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2.00 hours
Interval 0.67 to 3.0
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SECONDARY outcome
Timeframe: Up to 16 daysPopulation: All participants who received ISL on Day 2 are included.
The number of participants with AEs will be determined for 14 days after coadministration of methadone and ISL on Day 2.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Number of Participants With Adverse Events (AEs) Following Methadone + ISL Coadministration
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4 Participants
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SECONDARY outcome
Timeframe: Up to 15 daysPopulation: All participants who received ISL on Day 2 are included.
The number of participants discontinuing study therapy due to AEs after methadone + ISL on Day 2 will be determined.
Outcome measures
| Measure |
Methadone + ISL
n=13 Participants
Methadone-maintained participants (20 to 200 mg \[locally-provided\] QD from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Number of Participants Discontinuing Study Therapy Due to AEs Following Coadministration of Methadone and ISL
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0 Participants
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Adverse Events
Methadone + ISL
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Methadone + ISL
n=14 participants at risk
Methadone-maintained participants (20 to 200 mg \[locally-provided\] once daily \[QD\] from Day -14 to Day -1) receive their usual methadone dose on Day 1 and Days 3 to 14. On Day 2, methadone is coadministered with ISL 60 mg.
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Gastrointestinal disorders
Vomiting
|
7.1%
1/14 • Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2)
All enrolled study participants are included in analysis of all-cause mortality. All participants who received ISL on Day 2 are included in analysis of serious AEs (SAEs) and nonserious AEs.
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General disorders
Infusion site extravasation
|
7.1%
1/14 • Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2)
All enrolled study participants are included in analysis of all-cause mortality. All participants who received ISL on Day 2 are included in analysis of serious AEs (SAEs) and nonserious AEs.
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Metabolism and nutrition disorders
Increased appetite
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14.3%
2/14 • Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2)
All enrolled study participants are included in analysis of all-cause mortality. All participants who received ISL on Day 2 are included in analysis of serious AEs (SAEs) and nonserious AEs.
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Nervous system disorders
Headache
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14.3%
2/14 • Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2)
All enrolled study participants are included in analysis of all-cause mortality. All participants who received ISL on Day 2 are included in analysis of serious AEs (SAEs) and nonserious AEs.
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|
Psychiatric disorders
Anxiety
|
7.1%
1/14 • Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2)
All enrolled study participants are included in analysis of all-cause mortality. All participants who received ISL on Day 2 are included in analysis of serious AEs (SAEs) and nonserious AEs.
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|
Psychiatric disorders
Nightmare
|
7.1%
1/14 • Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2)
All enrolled study participants are included in analysis of all-cause mortality. All participants who received ISL on Day 2 are included in analysis of serious AEs (SAEs) and nonserious AEs.
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|
Skin and subcutaneous tissue disorders
Papule
|
7.1%
1/14 • Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2)
All enrolled study participants are included in analysis of all-cause mortality. All participants who received ISL on Day 2 are included in analysis of serious AEs (SAEs) and nonserious AEs.
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|
Skin and subcutaneous tissue disorders
Pruritus
|
7.1%
1/14 • Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2)
All enrolled study participants are included in analysis of all-cause mortality. All participants who received ISL on Day 2 are included in analysis of serious AEs (SAEs) and nonserious AEs.
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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