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

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ClinicalTrials.gov Identifier: NCT02217904
Recruitment Status : Completed
First Posted : August 15, 2014
Results First Posted : December 3, 2018
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
HIV-1 Drug: 1 mg islatravir Drug: 2 mg islatravir Drug: 10 mg islatravir Drug: 30 mg islatravir Drug: 0.5 mg islatravir Drug: 0.25 mg islatravir Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 17, 2015
Actual Primary Completion Date : May 11, 2017
Actual Study Completion Date : May 11, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: MK-8591




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02217904


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02217904    
Other Study ID Numbers: 8591-003
2014-002192-28 ( EudraCT Number )
MK-8591-003 ( Other Identifier: Merck Protocol Number )
First Posted: August 15, 2014    Key Record Dates
Results First Posted: December 3, 2018
Last Update Posted: August 12, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
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Islatravir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Anti-Retroviral Agents