A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8527 Monotherapy in Anti-Retroviral Therapy (ART)-Naïve, HIV-1 Infected Participants
Overview
- Phase
- Phase 1
- Intervention
- MK-8527
- Conditions
- Human Immunodeficiency Virus
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 20
- Locations
- 4
- Primary Endpoint
- Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a single-dose clinical study to evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-8527 in antiretroviral therapy (ART)-naïve participants living with human immunodeficiency virus type 1 (HIV-1) infection. The primary hypothesis is that, at a dose that is safe and generally well tolerated, MK-8527 will have antiretroviral activity as measured by a reduction from baseline in plasma HIV-1 ribonucleic acid (RNA) of ≥1.0 log10 copies/mL. A total of 4 arms was initially planned but Arm D was never initiated as the primary objectives were achieved following completion of Arms A to C.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is in good health other than HIV-1 infection
- •Is documented HIV-1 positive
- •Is ART-naïve, which is defined as not having received any marketed antiretroviral agent for treatment of HIV-1 infection (prior use of an ART for PrEP or investigational therapy is permitted if the last dose was ≥30 days prior to study drug administration)
- •Is willing to receive no other ART for the monitoring period of this study
Exclusion Criteria
- •Has a history of clinically significant endocrine, GI, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
- •Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study intervention, throughout the study, until the poststudy visit
- •Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit
Arms & Interventions
Panel A: MK-8527 1.0 mg
Participants receive a single oral dose of MK-8527 1.0 mg.
Intervention: MK-8527
Panel B: MK-8527 0.5 mg
Participants receive a single oral dose of MK-8527 0.5 mg.
Intervention: MK-8527
Panel C: MK-8527 0.25 mg
Participants receive a single oral dose of MK-8527 0.25 mg.
Intervention: MK-8527
Outcomes
Primary Outcomes
Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)
Time Frame: Baseline and 168 hours postdose on Day 1
The mean change from baseline in HIV-1 RNA counts at 168 hours after a single doses of MK-8527 is reported.
Number of Participants Experiencing ≥1 Adverse Event (AE)
Time Frame: Up to 28 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Discontinuing From Study Due to an AE
Time Frame: Up to 28 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Secondary Outcomes
- Area Under the Concentration-Time Curve From Predose to 168 Hours Postdose (AUC0-168) of MK-8527 Triphosphate (MK-8527-TP) in Peripheral Blood Mononuclear Cells (PBMCs)(Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose)
- Area Under the Concentration-Time Curve From Predose to Infinity (AUC0-inf) of MK-8527-TP in PBMCs(Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose)
- Area Under the Concentration-Time Curve From Predose to Last Measurable Concentration (AUC0-last) of MK-8527-TP in PBMCs(Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose)
- Maximum Concentration (Cmax) of MK-8527-TP in PBMCs(Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose)
- Concentration at 168 Hours Postdose (C168) of MK-8527-TP in PBMCs(168 hours postdose)
- Time to Maximum Concentration (Tmax) of MK-8527-TP in PBMCs(Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose)
- Apparent Terminal Half-life (t½) of MK-8527-TP in PBMCs(Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose)
- AUC0-inf of MK-8527 in Plasma(Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose)
- AUC0-last of MK-8527 in Plasma(Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose)
- Clast of MK-8527 in Plasma(Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose)
- Cmax of MK-8527 in Plasma(Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose)
- Tmax of MK-8527 in Plasma(Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose)
- Apparent t½ of MK-8527 in Plasma(Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose)
- Correlation Between Intracellular C168 of MK-8527-TP in PBMCs and Change From Baseline in Plasma HIV-1 RNA(Predose and 168 hours postdose)