MK-8527 Single-Dose Trial in HIV-1 Infected Participants (MK-8527-004)
- Registration Number
- NCT05494736
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Panel A: MK-8527 1.0 mg MK-8527 Participants receive a single oral dose of MK-8527 1.0 mg. Panel B: MK-8527 0.5 mg MK-8527 Participants receive a single oral dose of MK-8527 0.5 mg. Panel C: MK-8527 0.25 mg MK-8527 Participants receive a single oral dose of MK-8527 0.25 mg.
- Primary Outcome Measures
Name Time Method Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) 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) 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 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 Outcome Measures
Name Time Method 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 The AUC0-168 of MK-8527-TP in PBMCs is reported.
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 The MK-8527-TP AUC0-inf in PBMCs is reported.
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 The MK-8527-TP AUC0-last in PBMCs is reported.
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 The MK-8527-TP Cmax in PBMCs is reported.
Concentration at 168 Hours Postdose (C168) of MK-8527-TP in PBMCs 168 hours postdose The C168 of MK-8527-TP in PBMCs is reported.
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 The MK-8527-TP Tmax in PBMCs is reported.
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 The apparent t½ of MK-8527-TP in PBMCs is reported.
AUC0-inf of MK-8527 in Plasma Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose The AUC0-inf of MK-8527 in plasma is reported.
AUC0-last of MK-8527 in Plasma Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose The AUC0-last of MK-8527 in plasma is reported.
Clast of MK-8527 in Plasma Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose The Clast of MK-8527 in plasma is reported.
Cmax of MK-8527 in Plasma Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose The Cmax of MK-8527 in plasma is reported.
Tmax of MK-8527 in Plasma Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose The Tmax of MK-8527 in plasma is reported.
Apparent t½ of MK-8527 in Plasma Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose The apparent t½ of MK-8527 in plasma is reported.
Correlation Between Intracellular C168 of MK-8527-TP in PBMCs and Change From Baseline in Plasma HIV-1 RNA Predose and 168 hours postdose The correlation between between the C168 of MK-8527-TP in PBMCs and the change from baseline in plasma HIV-1 RNA levels 168 hours after dosing was calculated based on all pooled participants. All participants who complied with the protocol sufficiently to ensure that generated data will belikely to exhibit the effects of treatment, according to the underlying scientific model, are included. Participants with data below the LLOQ are excluded.
Trial Locations
- Locations (4)
ARENSIA Exploratory Medicine-Institutul National de Boli Infectioase Matei Bals ( Site 0004)
🇷🇴București, Bucuresti, Romania
Desmond Tutu Health Foundation ( Site 0001)
🇿🇦Cape Town, Western Cape, South Africa
Josha Research ( Site 0003)
🇿🇦Bloemfontein, Free State, South Africa
Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0002)
🇿🇦Johannesburg, Gauteng, South Africa