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| ID | Type | Description | Link |
|---|---|---|---|
| MK-8591-029 | Other Identifier | MSD Protocol Number |
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The present study is designed to determine the effect of islatravir (ISL) [MK-8591] on methadone pharmacokinetics (PK). The primary objective is to assess whether ISL impacts the area under the plasma concentration time curve from dosing to 24 hours postdose (AUC0-24) of S-methadone and R-methadone in participants on oral methadone therapy. It is hypothesized that the plasma AUC0-24hr for S- and R-methadone will be similar after methadone alone compared to methadone and ISL 60 mg coadministration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methadone + ISL | Experimental | Methadone-maintained participants (20 to 200 mg [locally-provided] once daily [QD] from Day -14 to Day -1 and Day 10 to Day 15) receive methadone 20 to 200 mg QD on Day 1 to Day 9; ISL 60 mg is co-administered with methadone on Day 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Islatravir | Drug | ISL 30 mg x 2 (60 mg total) capsules taken by mouth. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone | 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. | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
| Dose-Normalized AUC0-24 of S-Methadone | 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. | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Dose-Normalized Maximum Plasma Concentration (Cmax) of R-Methadone | 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. | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Centers of America, LLC ( Site 0002) | Hollywood | Florida | 33024 | United States | ||
| PRA Health Sciences ( Site 0001) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39648614 | Result | Matthews RP, Ankrom W, Handy W, Patel M, Matthews C, Xu Z, Gravesande K, Searle S, Schwartz H, Stoch SA, Iwamoto M. A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy. Clin Pharmacol Drug Dev. 2025 Jan;14(1):36-43. doi: 10.1002/cpdd.1492. Epub 2024 Dec 8. |
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Methadone-maintained participants were recruited at 2 study sites in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Methadone + ISL | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone | 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. | 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. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng*h/mL/mg | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
|
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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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 ISL 60 mg. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@msd.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 28, 2020 | Jun 1, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C558823 | islatravir |
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| Dose-Normalized Plasma Concentration 24 Hours Postdose (C24) of R-Methadone | 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. | Days 1 and 2: 24 hours postdose |
| Time to Maximum Plasma Concentration (Tmax) of R-Methadone | The Tmax of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
| Dose-Normalized Cmax of S-Methadone | 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. | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
| Dose-Normalized C24 of S-Methadone | 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. | Days 1 and 2: 24 hours postdose |
| Tmax of S-Methadone | The Tmax of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
| Dose-Normalized AUC0-24 of Total Methadone | 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. | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
| Dose-Normalized Cmax of Total Methadone | 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. | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
| Dose-Normalized C24 of Total Methadone | 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. | Days 1 and 2: 24 hours postdose |
| Tmax of Total Methadone | The Tmax of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
| Number of Participants With Adverse Events (AEs) Following Methadone + ISL Coadministration | The number of participants with AEs will be determined for 14 days after coadministration of methadone and ISL on Day 2. | Up to 16 days |
| Number of Participants Discontinuing Study Therapy Due to AEs Following Coadministration of Methadone and ISL | The number of participants discontinuing study therapy due to AEs after methadone + ISL on Day 2 will be determined. | Up to 15 days |
| Salt Lake City |
| Utah |
| 84124 |
| United States |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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|
| Primary | Dose-Normalized AUC0-24 of S-Methadone | 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. | 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. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng*h/mL/mg | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
|
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|
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| Secondary | Dose-Normalized Maximum Plasma Concentration (Cmax) of R-Methadone | 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. | 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. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng/mL/mg | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
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| Secondary | Dose-Normalized Plasma Concentration 24 Hours Postdose (C24) of R-Methadone | 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. | 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. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng/ml/mg | Days 1 and 2: 24 hours postdose |
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| Secondary | Time to Maximum Plasma Concentration (Tmax) of R-Methadone | The Tmax of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). | 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. | Posted | Median | Full Range | hours | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
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| Secondary | Dose-Normalized Cmax of S-Methadone | 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. | 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. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng/mL/mg | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
|
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| Secondary | Dose-Normalized C24 of S-Methadone | 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. | 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. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng/ml/mg | Days 1 and 2: 24 hours postdose |
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| Secondary | Tmax of S-Methadone | The Tmax of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). | 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. | Posted | Median | Full Range | hours | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
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|
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| Secondary | Dose-Normalized AUC0-24 of Total Methadone | 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. | 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. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng*h/mL/mg | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
|
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|
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| Secondary | Dose-Normalized Cmax of Total Methadone | 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. | 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. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng/mL/mg | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
|
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|
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| Secondary | Dose-Normalized C24 of Total Methadone | 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. | 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. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng/ml/mg | Days 1 and 2: 24 hours postdose |
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| Secondary | Tmax of Total Methadone | The Tmax of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). | 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. | Posted | Median | Full Range | hours | Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose |
|
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| Secondary | Number of Participants With Adverse Events (AEs) Following Methadone + ISL Coadministration | The number of participants with AEs will be determined for 14 days after coadministration of methadone and ISL on Day 2. | All participants who received ISL on Day 2 are included. | Posted | Count of Participants | Participants | Up to 16 days |
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| Secondary | Number of Participants Discontinuing Study Therapy Due to AEs Following Coadministration of Methadone and ISL | The number of participants discontinuing study therapy due to AEs after methadone + ISL on Day 2 will be determined. | All participants who received ISL on Day 2 are included. | Posted | Count of Participants | Participants | Up to 15 days |
|
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|
| 0 |
| 14 |
| 0 |
| 14 |
| 4 |
| 14 |
| Infusion site extravasation | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Increased appetite | Metabolism and nutrition disorders | MedDRA 24.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
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| Papule | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.