- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02217904
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
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
30
Phase
- 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
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 |
Intervention / Treatment |
---|---|
Experimental: Islatravir 1 mg
Single oral dose of islatravir 1 mg
|
Single oral dose of 1 mg islatravir administered following ≥8 hour fast
Other Names:
|
Experimental: Islatravir 2 mg
Single oral dose of islatravir 2 mg
|
Single oral dose of 2 mg islatravir administered following ≥8 hour fast
Other Names:
|
Experimental: Islatravir 10 mg
Single oral dose of islatravir 10 mg
|
Single oral dose of 10 mg islatravir administered following ≥8 hour fast
Other Names:
|
Experimental: Islatravir 30 mg
Single oral dose of islatravir 30 mg
|
Single oral dose of 30 mg islatravir administered following ≥8 hour fast
Other Names:
|
Experimental: Islatravir 0.5 mg
Single oral dose of islatravir 0.5 mg
|
Single oral dose of 0.5 mg islatravir administered following ≥8 hour fast
Other Names:
|
Experimental: Islatravir 0.25 mg
Single oral dose of islatravir 0.25 mg
|
Single oral dose of 0.25 mg islatravir administered following ≥8 hour fast
Other Names:
|
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.
|
Single oral dose of 30 mg islatravir administered following ≥8 hour fast
Other Names:
|
What is the study measuring?
Primary Outcome Measures
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
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
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.
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)
September 17, 2015
Primary Completion (Actual)
May 11, 2017
Study Completion (Actual)
May 11, 2017
Study Registration Dates
First Submitted
August 13, 2014
First Submitted That Met QC Criteria
August 13, 2014
First Posted (Estimate)
August 15, 2014
Study Record Updates
Last Update Posted (Actual)
August 12, 2019
Last Update Submitted That Met QC Criteria
July 24, 2019
Last Verified
July 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID 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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