A Study of MK-8527 in Human Immunodeficiency Type 1 Virus (HIV-1) Infected Participants (MK-8527-002)
- Registration Number
- NCT03615183
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study will evaluate the anti-retroviral activity of MK-8527 in HIV-1 infected, ART-naïve participants. The primary hypothesis is that MK-8527 has superior anti-retroviral activity compared to placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours postdose.
- Detailed Description
Up to five panels (Panels A-E) of 6 participants each will be enrolled in a sequential manner. In each panel, participants will receive a single dose of MK-8527 up to 50 mg. Historical data from previous single does studies will be used for placebo (control) comparisons.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Panel A: 10 mg MK-8527 MK-8527 Single oral dose of 10 mg MK-8527 capsule after an 8-hour fast Panel B: 3 mg MK-8527 MK-8527 Single oral dose of 3 mg MK-8527 capsule after an 8-hour fast Panel C: 1 mg MK-8527 MK-8527 Single oral dose of 1 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels. Panel D: ≤50 mg MK-8527 MK-8527 Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels. Panel E: ≤50 mg MK-8527 MK-8527 Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels.
- Primary Outcome Measures
Name Time Method Change From Baseline in Plasma HIV-1 RNA Baseline and 168 hours postdose Blood samples were taken to determine HIV-1 RNA levels at Predose (baseline) and 168 hours postdose. Data were fitted with a longitudinal data analysis (LDA) model containing fixed effects for treatment, time and treatment by time interaction, and a random effect for participant.The change from baseline in plasma HIV-1 RNA in participants administered MK-8527 was calculated and results were compared with historical placebo data.
Percentage of Participants Who Were Discontinued From the Study Due to an AE Up to 28 days An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE will be summarized.
Percentage of Participants Who Report 1 or More Adverse Events (AEs) Up to 28 days An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that reported at least 1 AE will be summarized.
- Secondary Outcome Measures
Name Time Method Maximum Concentration (Cmax) of MK-8527-TP in PBMC Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Cmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time to Cmax (Tmax) of MK-8527-TP in PBMC Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Tmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Concentration at 168 Hours (C168) of MK-8527-TP in PBMC 168 hours postdose for each panel Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-last of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-Inf of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC) Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527-triphosphate (MK-8527-TP) in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% confidence intervals (CI) for the means were constructed on the natural log scale and referenced the t-distribution.
Time to Cmax (Tmax) of MK-8527 in Plasma Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose Blood samples were taken at Predose, up to 168 hours postdose to determine the Tmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Apparent Terminal Half Life (t1/2) of MK-8527-TP in PBMC Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose Blood samples were taken at Predose, up to approximately 28 days postdose to determine the t1/2 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527 in Plasma Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-last of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527 in Plasma Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-inf of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Maximum Concentration (Cmax) of MK-8527 in Plasma Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose Blood samples were taken at Predose, up to 168 hours postdose to determine the Cmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Concentration at 168 Hours (C168) of MK-8527 in Plasma 168 hours postdose Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Apparent Terminal Half Life (t1/2) of MK-8527 in Plasma Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose Blood samples were taken at Predose, up to 168 hours postdose to determine the t1/2 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Trial Locations
- Locations (1)
Matei Bals Infectious Diseases Institute ( Site 0001)
🇷🇴Bucharest, Romania