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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Panel A: MK-8527 1.0 mg
Participants receive a single oral dose of MK-8527 1.0 mg.
干预措施: MK-8527 (Drug)
Panel B: MK-8527 0.5 mg
Participants receive a single oral dose of MK-8527 0.5 mg.
干预措施: MK-8527 (Drug)
Panel C: MK-8527 0.25 mg
Participants receive a single oral dose of MK-8527 0.25 mg.
干预措施: MK-8527 (Drug)
结局指标
主要结局
Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)
时间窗: 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)
时间窗: 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
时间窗: 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.
次要结局
- 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)