Clinical trial NCT02217904: A Study of Islatravir (MK-8591) in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus-1 Infected Participants (MK-8591-003)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-08-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose
timeFrame: Baseline and 168 hours (7 days) post-dose
measure: Number of Participants With One or More Adverse Events
timeFrame: Up to 21 days post-dose
Secondary outcomes:
measure: Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr)
timeFrame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
measure: Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells
timeFrame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
measure: Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr)
timeFrame: 168 hours after islatravir administration
measure: Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells
timeFrame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
measure: Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells
timeFrame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
measure: Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr)
timeFrame: 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.
measure: Maximum Plasma Concentration (Cmax) of Islatravir
timeFrame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
measure: Time to Maximum Plasma Concentration (Tmax) of Islatravir
timeFrame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
measure: Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma
timeFrame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Schurmann D, Rudd DJ, Zhang S, De Lepeleire I, Robberechts M, Friedman E, Keicher C, Huser A, Hofmann J, Grobler JA, Stoch SA, Iwamoto M, Matthews RP. Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial. Lancet HIV. 2020 Mar;7(3):e164-e172. doi: 10.1016/S2352-3018(19)30372-8. Epub 2020 Jan 3.