CClinicalTrials.gg
Sign In
CompletedNCT04568603Updated Jan 28, 2025Results posted

Islatravir and Methadone Pharmacokinetics (MK-8591-029)

A Phase 1 interventional study of Islatravir in HIV-1 Infection, sponsored by Merck Sharp & Dohme LLC. Completed at 2 sites in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-01-28.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
14
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study 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 methadone alone compared to methadone and ISL 60 mg coadministration.

02

Conditions studied

  • HIV-1 Infection
03

In context

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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.
  • Has a negative human immunodeficiency virus (HIV) antigen/antibody test at screening
  • For male participants, follows contraception guidance consistent with local regulations
  • For female participants:
  • Is not a woman of childbearing potential (WOCBP) or
  • Is a WOCBP and using acceptable contraception or is abstinent
  • 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

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
  • 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
  • Has a history of cancer (malignancy)
  • 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
  • Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the screening visit
  • 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)
  • Has participated in another investigational study within 4 weeks (or 5 half-lives) prior to the prestudy (screening) visit.
  • 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
  • Does not limit smoking to no more than 10 cigarettes per day while in the clinical research unit (CRU)
  • Consumes greater than 3 glasses of alcoholic beverages per day
  • 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
  • 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
  • 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
05

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
14 participants (actual)

Study arms

  • Experimental
    Methadone + ISL

    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.

    Drug: Islatravir

Interventions

  • DrugIslatravir

    ISL 30 mg x 2 (60 mg total) capsules taken by mouth.

    Also known as: MK-8591

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

  2. 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.

    Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

Secondary outcomes

  1. 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.

    Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

  2. 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.

    Time frame: Days 1 and 2: 24 hours postdose

  3. 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).

    Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

  4. 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.

    Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

  5. 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.

    Time frame: Days 1 and 2: 24 hours postdose

  6. Tmax of S-Methadone

    The Tmax of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).

    Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

  7. 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.

    Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

  8. 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.

    Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

  9. 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.

    Time frame: Days 1 and 2: 24 hours postdose

  10. Tmax of Total Methadone

    The Tmax of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).

    Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose

  11. 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.

    Time frame: Up to 16 days

  12. 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.

    Time frame: Up to 15 days

07

Results

Posted Dec 11, 2023

Participant flow

Methadone-maintained participants were recruited at 2 study sites in the United States.

Participant flow — Overall Study
MilestoneMethadone + ISL
Started14
Received isl on day 213
Completed13
Not completed1
Withdrew: Physician decision1

Outcome measures

PrimaryDose-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.

Time frame:
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Reported as:
Geometric least squares mean · ng*h/mL/mg
Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone
ng*h/mL/mgMethadone + ISL
Day 1: Methadone Alone61.9 (49.3 to 77.7)
Day 2: Methadone + ISL63.9 (52.2 to 78.1)
Statistical analysis
  • Methadone + ISL · Gmr: 1.03 · 90% CI 1.00 to 1.07
PrimaryDose-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.

Time frame:
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Reported as:
Geometric least squares mean · ng*h/mL/mg
Dose-Normalized AUC0-24 of S-Methadone
ng*h/mL/mgMethadone + ISL
Day 1: Methadone Alone63.1 (48.9 to 81.5)
Day 2: Methadone + ISL65.1 (51.7 to 82.0)
Statistical analysis
  • Methadone + ISL · Gmr: 1.03 · 90% CI 0.99 to 1.07
SecondaryDose-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.

Time frame:
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Reported as:
Geometric least squares mean · ng/mL/mg
Dose-Normalized Maximum Plasma Concentration (Cmax) of R-Methadone
ng/mL/mgMethadone + ISL
Day 1: Methadone Alone3.64 (3.00 to 4.43)
Day 2: Methadone + ISL3.71 (3.14 to 4.40)
Statistical analysis
  • Methadone + ISL · Gmr: 1.02 · 90% CI 0.96 to 1.09
SecondaryDose-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.

Time frame:
Days 1 and 2: 24 hours postdose
Reported as:
Geometric least squares mean · ng/ml/mg
Dose-Normalized Plasma Concentration 24 Hours Postdose (C24) of R-Methadone
ng/ml/mgMethadone + ISL
Day 1: Methadone Alone2.09 (1.63 to 2.69)
Day 2: Methadone + ISL2.23 (1.78 to 2.78)
Statistical analysis
  • Methadone + ISL · Gmr: 1.06 · 90% CI 1.03 to 1.10
SecondaryTime to Maximum Plasma Concentration (Tmax) of R-Methadone

The Tmax of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).

Time frame:
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Reported as:
Median · hours
Time to Maximum Plasma Concentration (Tmax) of R-Methadone
hoursMethadone + ISL
Day 1: Methadone Alone2.00 (1.47 to 3.00)
Day 2: Methadone + ISL2.00 (0.67 to 4.00)
SecondaryDose-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.

Time frame:
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Reported as:
Geometric least squares mean · ng/mL/mg
Dose-Normalized Cmax of S-Methadone
ng/mL/mgMethadone + ISL
Day 1: Methadone Alone4.25 (3.45 to 5.25)
Day 2: Methadone + ISL4.31 (3.49 to 5.32)
Statistical analysis
  • Methadone + ISL · Gmr: 1.01 · 90% CI 0.94 to 1.09
SecondaryDose-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.

Time frame:
Days 1 and 2: 24 hours postdose
Reported as:
Geometric least squares mean · ng/ml/mg
Dose-Normalized C24 of S-Methadone
ng/ml/mgMethadone + ISL
Day 1: Methadone Alone1.91 (1.44 to 2.54)
Day 2: Methadone + ISL2.07 (1.60 to 2.68)
Statistical analysis
  • Methadone + ISL · Gmr: 1.08 · 90% CI 1.04 to 1.13
SecondaryTmax of S-Methadone

The Tmax of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).

Time frame:
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Reported as:
Median · hours
Tmax of S-Methadone
hoursMethadone + ISL
Day 1: Methadone Alone1.50 (1.02 to 3.00)
Day 2:Methadone + ISL2.00 (0.67 to 3.00)
SecondaryDose-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.

Time frame:
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Reported as:
Geometric least squares mean · ng*h/mL/mg
Dose-Normalized AUC0-24 of Total Methadone
ng*h/mL/mgMethadone + ISL
Day 1: Methadone Alone126 (99.1 to 159)
Day 2: Methadone + ISL129 (105 to 160)
Statistical analysis
  • Methadone + ISL · Gmr: 1.03 · 90% CI 0.99 to 1.07
SecondaryDose-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.

Time frame:
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Reported as:
Geometric least squares mean · ng/mL/mg
Dose-Normalized Cmax of Total Methadone
ng/mL/mgMethadone + ISL
Day 1: Methadone Alone7.91 (6.48 to 9.66)
Day 2: Methadone + ISL8.02 (6.64 to 9.68)
Statistical analysis
  • Methadone + ISL · Gmr: 1.01 · 90% CI 0.95 to 1.08
SecondaryDose-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.

Time frame:
Days 1 and 2: 24 hours postdose
Reported as:
Geometric least squares mean · ng/ml/mg
Dose-Normalized C24 of Total Methadone
ng/ml/mgMethadone + ISL
Day 1: Methadone Alone4.03 (3.10 to 5.23)
Day 2: Methadone + ISL4.32 (3.42 to 5.45)
Statistical analysis
  • Methadone + ISL · Gmr: 1.07 · 90% CI 1.03 to 1.11
SecondaryTmax of Total Methadone

The Tmax of total methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL).

Time frame:
Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Reported as:
Median · hours
Tmax of Total Methadone
hoursMethadone + ISL
Day 1: Methadone Alone2.00 (1.47 to 3.00)
Day 2: Methadone + ISL2.00 (0.67 to 3.00)
SecondaryNumber 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.

Time frame:
Up to 16 days
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs) Following Methadone + ISL Coadministration
ParticipantsMethadone + ISL
Number of Participants With Adverse Events (AEs) Following Methadone + ISL Coadministration4
SecondaryNumber 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.

Time frame:
Up to 15 days
Reported as:
Count of participants · Participants
Number of Participants Discontinuing Study Therapy Due to AEs Following Coadministration of Methadone and ISL
ParticipantsMethadone + ISL
Number of Participants Discontinuing Study Therapy Due to AEs Following Coadministration of Methadone and ISL0

Adverse events

Collected over Up to 16 days (up to 14 days after methadone + ISL coadministration on Day 2). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Methadone + ISL0/14 (0%)0/14 (0%)4/14 (28.6%)
Most frequent other events
Most frequent other events
EventMethadone + ISL
Increased appetiteMetabolism and nutrition disorders2/14
HeadacheNervous system disorders2/14
VomitingGastrointestinal disorders1/14
Infusion site extravasationGeneral disorders1/14
AnxietyPsychiatric disorders1/14
NightmarePsychiatric disorders1/14
PapuleSkin and subcutaneous tissue disorders1/14
PruritusSkin and subcutaneous tissue disorders1/14

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Methadone + ISL
Mean43.5 ± 12.0
Sex: Female, Male
Sex: Female, Male(Participants)Methadone + ISL
Female5
Male9
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Methadone + ISL
Hispanic or Latino3
Not Hispanic or Latino11
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Methadone + ISL
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander1
Black or African American0
White12
More than one race1
Unknown or Not Reported0
08

Study locations

2 sites
  • Research Centers of America, LLC ( Site 0002)
    Hollywood, Florida 33024, United States
  • PRA Health Sciences ( Site 0001)
    Salt Lake City, Utah 84124, United States
09

References and documents

Publications

  • 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. PubMed 39648614 ↗

Study documents

  • Protocol and statistical analysis plan · Aug 28, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 28, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04568603
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Sep 29, 2020
Start date
Oct 16, 2020
Primary completion
Jul 9, 2021
Completion
Jul 9, 2021
Results posted
Dec 11, 2023
Last update
Jan 28, 2025

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Merck Sharp & Dohme LLC

Start the discussion