Islatravir and Methadone Pharmacokinetics (MK-8591-029)
Study Details
Study Description
Brief Summary
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 single-dose co-administration of methadone + ISL.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Methadone + ISL Methadone-maintained participants (20 to 200 mg 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 and ISL 60 mg once on Day 2. |
Drug: Islatravir
ISL 30 mg x 2 (60 mg total) capsules taken by mouth.
Other Names:
Drug: Methadone
Methadone 20 to 200 mg QD taken by mouth.
|
Outcome Measures
Primary Outcome Measures
- Dose-Normalized Area Under the Plasma Concentration Time Curve from 0-24 Hours Postdose (AUC0-24hr) of S-Methadone [Day 1]
The AUC0-24hr of S-methadone will be determined on Day 1.
- Dose-Normalized AUC0-24hr of R-Methadone [Day 1]
The AUC0-24hr of R-methadone will be determined on Day 1.
- Dose-Normalized AUC0-24hr of S-Methadone + ISL [Day 1]
The AUC0-24hr of S-methadone with ISL 60 mg will be determined on Day 2.
- Dose-Normalized AUC0-24hr of R-Methadone + ISL [Day 1]
The AUC0-24hr of R-methadone with ISL 60 mg will be determined on Day 2.
Secondary Outcome Measures
- Maximum Plasma Concentration (Cmax) of R-Methadone [Day 1]
The Cmax of R-methadone will be determined on Day 1.
- Plasma Concentration 24 Hours Postdose (C24hr) of R-Methadone [Day 1]
The C24hr of R-methadone will be determined on Day 1.
- Time to Maximum Plasma Concentration (Tmax) of R-Methadone [Day 1]
The Tmax of R-methadone will be determined on Day 1.
- Cmax of R-Methadone + ISL [Day 2]
The Cmax of R-methadone + ISL 60 mg will be determined on Day 2.
- C24hr of R-Methadone + ISL [Day 2]
The C24hr of R-methadone + ISL 60 mg will be determined on Day 2.
- Tmax of R-Methadone + ISL [Day 2]
The Tmax of R-methadone + ISL 60 mg will be determined on Day 2.
- Cmax of S-Methadone [Day 1]
The Cmax of S-methadone will be determined on Day 1.
- C24hr of S-Methadone [Day 1]
The C24hr of S-methadone will be determined on Day 1.
- Tmax of S-Methadone [Day 1]
The Tmax of S-methadone will be determined on Day 1.
- Cmax of S-Methadone + ISL [Day 2]
The Cmax of S-methadone + ISL 60 mg will be determined on Day 2.
- C24hr of S-Methadone + ISL [Day 2]
The C24hr of S-methadone + ISL 60 mg will be determined on Day 2.
- Tmax of S-Methadone + ISL [Day 2]
The Tmax of S-methadone + ISL 60 mg will be determined on Day 2.
- Cmax of Methadone [Day 1]
The Cmax of total methadone will be determined on Day 1.
- C24hr of Methadone [Day 1]
The C24hr of total methadone will be determined on Day 1.
- Tmax of Methadone [Day 1]
The Tmax of total methadone will be determined on Day 1.
- Cmax of Methadone + ISL [Day 2]
The Cmax of total methadone + ISL 60 mg will be determined on Day 2.
- C24hr of Methadone + ISL [Day 2]
The C24hr of total methadone + ISL 60 mg will be determined on Day 2.
- Tmax of Methadone + ISL [Day 2]
The Tmax of total methadone + ISL 60 mg will be determined on Day 2.
- Dose-Normalized AUC0-24hr of Total Methadone [Day 1]
The AUC0-24hr of total methadone will be determined on Day 1.
- Dose-Normalized AUC0-24hr of Total Methadone + ISL [Day 2]
The AUC0-24hr of total methadone + ISL 60 mg will be determined on Day 2.
- Percentage of Participants with Adverse Events (AEs) [Up to 16 days]
The percentage of participants with AEs will be determined.
- Percentage of Participants Discontinuing Study Therapy due to AEs [Up to 16 days]
The percentage of participants discontinuing study therapy due to AEs will be determined.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has a body mass index (BMI) > 18 and ≤ 35 kg/m^2
-
Is in good health based on laboratory safety tests obtained at the screening visit and prior to administration of study drug
-
Is in good health based on medical history, physical examination, vital sign measurements, and electrocardiograms (ECGs) performed prior to randomization.
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Has a negative human immunodeficiency virus (HIV) antigen/antibody test at screening
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For male participants, follows contraception guidance consistent with local regulations
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For female participants:
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Is not a woman of childbearing potential (WOCBP) or
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Is a WOCBP and using acceptable contraception or is abstinent
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Is reliably participating in a methadone maintenance program for at least two (2) months prior to Day 1
-
Agrees to not change their current maintenance methadone dose of 20-200 mg administered as a single daily dose
Exclusion Criteria:
-
Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
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Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years
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Has a history of cancer (malignancy)
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Has a history of significant multiple and/or severe allergies (eg, food, drug, latex) or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or non-prescription drugs or food
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Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the screening visit
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With the exception of methadone, is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to the first dose of the 14-day methadone maintenance run-in phase prior to Day 1, throughout the trial, until the AE follow-up call (Day 16)
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Has participated in another investigational study within 4 weeks (or 5 half-lives) prior to the prestudy (screening) visit.
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Has a QTc interval >450 msec (males) or >470 msec (females), has a history of risk factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of long QT syndrome), has uncorrected hypokalemia or hypomagnesemia, is taking concomitant medications that prolong the QT/QTc interval other than methadone
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Does not limit smoking to no more than 10 cigarettes per day while in the clinical research unit (CRU)
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Consumes greater than 3 glasses of alcoholic beverages
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Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day
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With the exception of tetrahydrocannabinol (THC), has a positive screen for drugs with a high potential for abuse such as cocaine, amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines (with the exception noted in exclusion criteria 7), or opiates/opioids on Day -1
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Presents any concern by the investigator regarding safe participation in the study or for any other reason the investigator considers the participant inappropriate for participation in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Centers of America, LLC ( Site 0002) | Hollywood | Florida | United States | 33024 |
| 2 | PRA Health Sciences ( Site 0001) | Salt Lake City | Utah | United States | 84124 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8591-029
- MK-8591-029