Phase 1
Completed N=30
A Study of Islatravir (MK-8591) in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus-1 Infected Participants (MK-8591-003)
Source: ClinicalTrials.gov NCT02217904 ↗Enrolled (actual)
30
Serious AEs
0.0%
Results posted
Dec 2018
Primary outcomePrimary: Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose — -1.67; -1.35; -1.60; -1.30 log10 copies/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose |
-1.67; -1.35; -1.60; -1.30; -1.20 | — |
| PRIMARY Number of Participants With One or More Adverse Events |
5; 5; 6; 5; 6 | — |
| SECONDARY Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr) |
227; 46.9; 926; 35.9; 23.1 | — |
| SECONDARY Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells |
2.81; 0.495; 8.9; 0.408; 0.263 | — |
| SECONDARY Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr) |
0.983; 0.188; 4.83; 0.164; 0.116 | — |
| SECONDARY Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells |
12; 8; 24; 8; 12 | — |
| SECONDARY Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells |
128; 120; 78.5; 118; 95.3 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr) |
1020; 143; 3020; 88.3; 38.3 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Islatravir |
235; 43.8; 678; 38.8; 20.3 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) of Islatravir |
1; 0.5; 0.75; 0.5; 0.5 | — |
| SECONDARY Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma |
59.7; 47.4; 56.8; 10.4; 2.31 | — |
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
Data sourced from ClinicalTrials.gov (NCT02217904). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.