HIV-1 InfectionPhase 1NCT04568603
Islatravir and Methadone Pharmacokinetics (MK-8591-029)
A Phase 1 study testing Islatravir in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- Islatravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesUnited States
- Study dates
- 16 Oct 2020to 9 Jul 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Research Centers of America, LLC ( Site 0002)
Hollywood, Florida, 33024
PRA Health Sciences ( Site 0001)
Salt Lake City, Utah, 84124
About this study
Official title: A Clinical Trial to Study the Effect of a Single Dose of Islatravir (MK-8591) on the Pharmacokinetics of Methadone
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.
- Conditions
- HIV-1 Infection
- Being tested
- Islatravir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IslatravirDrug
Also called MK-8591
ISL 30 mg x 2 (60 mg total) capsules taken by mouth.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Islatravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Secondary outcomes (12)
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.
Measured: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Up to 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2020
- Study start16 Oct 2020
- Primary completion9 Jul 2021
- Study completion9 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04568603
- Sponsor's protocol ID
- 8591-029
- Other IDs
- MK-8591-029
- Status last verified
- Jan 2025
- First submitted
- 23 Sep 2020
- Last updated
- 28 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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 at a glance
From the registry record, last updated by the sponsor on 28 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial to Study the Effect of a Single Dose of Islatravir (MK-8591) on the Pharmacokinetics of Methadone
- ClinicalTrials.gov ID
- NCT04568603
- Acronym / sponsor ID
- 8591-029
- Conditions
- HIV-1 Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 16 Oct 2020 (actual)
- Primary completion
- 9 Jul 2021 (actual)
- Study completion
- 9 Jul 2021 (actual)
- First posted
- 29 Sep 2020 (actual)
- Results
- Posted 11 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Methadone + ISL | Experimental | Drug: IslatravirMethadone-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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IslatravirAlso: MK-8591ISL 30 mg x 2 (60 mg total) capsules taken by mouth. | Drug | Methadone + ISL |
Primary outcome
Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone
Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
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.
Dose-Normalized AUC0-24 of S-Methadone
Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
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.
12 secondary outcomes
Dose-Normalized Maximum Plasma Concentration (Cmax) of R-Methadone
Time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
Dose-Normalized Plasma Concentration 24 Hours Postdose (C24) of R-Methadone
Time frame: Days 1 and 2: 24 hours postdose
Time to Maximum Plasma Concentration (Tmax) of R-Methadone
Time frame: 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
Time frame: 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
Time frame: Days 1 and 2: 24 hours postdose
Tmax of S-Methadone
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Days 1 and 2: 24 hours postdose
Tmax of Total Methadone
Time frame: 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
Time frame: Up to 16 days
Number of Participants Discontinuing Study Therapy Due to AEs Following Coadministration of Methadone and ISL
Time frame: Up to 15 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 39648614Matthews 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.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Islatravir in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone (time frame: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04568603, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2025.