A Study of Islatravir (MK-8591) in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus-1 Infected Participants (MK-8591-003)

July 24, 2019 updated by: Merck Sharp & Dohme LLC

A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8591 Monotherapy in Anti-Retroviral Therapy (ART)-Naive, HIV-1 Infected Patients

This study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral therapy (ART) activity of islatravir (MK-8591) monotherapy in ART-naive, human immunodeficiency virus-1 (HIV-1) infected participants. The primary hypothesis is that at a safe and tolerable dose of islatravir, the true mean difference in the plasma HIV-1 ribonucleic acid (RNA) reduction from baseline between islatravir and placebo is at least 0.5 log (base10) copies/mL.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Non-pregnant, non-breast feeding, postmenopausal or surgically sterile female
  • Female with reproductive potential agrees to use (or have male partner use) two acceptable methods of birth control
  • Male agrees to use acceptable method of contraception during study and for 90 days after last dose of trial drug
  • Has stable baseline health, other than HIV infection
  • Has no significantly abnormal electrocardiogram
  • Is HIV-1 positive
  • Have a screening plasma HIV-1 RNA ≥ 10,000 copies/mL within 30 days prior to the treatment phase of this study. For inclusion in Panel Islatravir Extended Observation, participants must also have a screening plasma HIV-1 RNA ≤ 25,000 copies/mL within 30 days prior to the treatment phase.
  • Is ART naive
  • Has not received any investigational agent or marketed ART within 30 days of trial drug administration
  • Is diagnosed with HIV-1 infection >= 3 months prior to screening
  • Is willing to receive no other ART during treatment phase of study
  • Has no evidence of mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs)

Exclusion Criteria:

  • Is mentally or legally institutionalized/incapacitated, or has significant emotional problems, or has a history of clinically significant psychiatric disorder of the last 5 years
  • Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, major neurological abnormalities or diseases
  • Has a history of cancer (malignancy)
  • Has a history of significant multiple and/or severe allergies, or had an anaphylactic reaction to drugs or food
  • Is positive for hepatitis B surface antigen
  • Has a history of chronic Hepatitis C
  • Had major surgery or lost 500 mL of blood with 4 weeks prior to screening visit
  • Has participated in another investigational trial within 4 weeks prior to dosing visit
  • Will use any medications, prescribed drugs, or herbal remedies 4 weeks prior to dosing of trial drug, up to the post-trial visit
  • Consumes excessive amounts of alcohol, caffeinated beverages, or tobacco products
  • Uses illicit drugs or has a history of drug abuse within the prior 2 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Islatravir 1 mg
Single oral dose of islatravir 1 mg
Drug: 1 mg islatravir
Single oral dose of 1 mg islatravir administered following ≥8 hour fast
Other Names:
  • MK-8591
Experimental: Islatravir 2 mg
Single oral dose of islatravir 2 mg
Drug: 2 mg islatravir
Single oral dose of 2 mg islatravir administered following ≥8 hour fast
Other Names:
  • MK-8591
Experimental: Islatravir 10 mg
Single oral dose of islatravir 10 mg
Drug: 10 mg islatravir
Single oral dose of 10 mg islatravir administered following ≥8 hour fast
Other Names:
  • MK-8591
Experimental: Islatravir 30 mg
Single oral dose of islatravir 30 mg
Drug: 30 mg islatravir
Single oral dose of 30 mg islatravir administered following ≥8 hour fast
Other Names:
  • MK-8591
Experimental: Islatravir 0.5 mg
Single oral dose of islatravir 0.5 mg
Drug: 0.5 mg islatravir
Single oral dose of 0.5 mg islatravir administered following ≥8 hour fast
Other Names:
  • MK-8591
Experimental: Islatravir 0.25 mg
Single oral dose of islatravir 0.25 mg
Drug: 0.25 mg islatravir
Single oral dose of 0.25 mg islatravir administered following ≥8 hour fast
Other Names:
  • MK-8591
Experimental: Islatravir 30 mg Extended Observation
Single oral dose of 30 mg islatravir administered following >8 hour fast. Participants will be closely monitored for viral load for up to approximately 21 days prior to starting standard of care ART.
Drug: 30 mg islatravir
Single oral dose of 30 mg islatravir administered following ≥8 hour fast
Other Names:
  • MK-8591

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose
Time Frame: Baseline and 168 hours (7 days) post-dose
Plasma HIV-1 RNA was measured using the Roche COBAS Ampliprep/COBAS TaqMan HIV-1 test v.2.0, which has a linear range from 20 to 10,000,000 copies/mL. The lower limit of detection has 100% specificity at 20 copies/mL. Additionally, the test increases the probability of detection and expands coverage by targeting two highly conserved regions of the HIV-1 genome to compensate for the possibility of mutations or mismatches.
Baseline and 168 hours (7 days) post-dose
Number of Participants With One or More Adverse Events
Time Frame: Up to 21 days post-dose
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Up to 21 days post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr)
Time Frame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine AUC0-168hr.
4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells
Time Frame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine Cmax.
4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr)
Time Frame: 168 hours after islatravir administration
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine C168hr.
168 hours after islatravir administration
Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells
Time Frame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine TMax.
4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells
Time Frame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine apparent terminal t1/2.
4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr)
Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration. Value at 168 hours was extrapolated.
Blood was collected for the determination of AUC0-168hr of islatravir in plasma.
Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration. Value at 168 hours was extrapolated.
Maximum Plasma Concentration (Cmax) of Islatravir
Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Blood was collected for the determination of Cmax of islatravir in plasma.
Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Time to Maximum Plasma Concentration (Tmax) of Islatravir
Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Blood was collected for the determination of Tmax of islatravir in plasma.
Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma
Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Blood was collected for the determination of apparent terminal t1/2 of islatravir in plasma.
Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 17, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 11, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 11, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 13, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 15, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 12, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 8591-003
  • 2014-002192-28 (EudraCT Number)
  • MK-8591-003 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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