A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti- Retroviral Activity of MK-8583 Monotherapy in Anti-Retroviral Therapy (ART)-Naïve, HIV-1 Infected Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Participants With at Least One Adverse Event (AE)
研究概览
简要总结
This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-retroviral therapy (ART) activity of the tenofovir prodrug, MK-8583 monotherapy in ART-naïve, HIV-1 infected participants. The primary hypothesis is that at a dose that is sufficiently safe and generally well tolerated, MK-8583 has superior anti-retroviral activity compared to historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours post-dose.
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
- •Male with female partner(s) of child-bearing potential use required methods of birth control.
- •Female of reproductive potential must demonstrate a nongravid state at the pretrial (screening) visit and agree to use acceptable methods of birth control beginning at the pretrial (screening) visit, throughout the trial and until 30 days following cessation of treatment.
- •Postmenopausal female, defined as without menses for at least 1 year and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial (screening).
- •Surgically sterile female's status is post hysterectomy or oophorectomy.
- •Is documented HIV-1 positive
- •Is diagnosed with HIV-1 infection ≥ 3 months prior to screening.
- •Is ART-naïve, defined as having never received any anti-retroviral agent; or ≤ 30 consecutive days of an investigational anti-retroviral agent, excluding a nucleoside reverse transcriptase inhibitor (NRTI), or ≤ 60 consecutive days of combination ART not including a NRTI.
排除标准
- •Is mentally or legally institutionalized/incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder over the last 5 years.
- •Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases.
- •Has a history of cancer (malignancy).
- •Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.
- •Is positive for Hepatitis B surface antigen.
- •Has a history of chronic Hepatitis C unless there has been documented cure.
- •Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
- •Has participated in another investigational trial within 4 weeks or 5 half-lives, whichever is greater, prior to the pre-trial (screening) visit.
- •Uses or anticipates using any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of trial drug, throughout the trial, until the post-trial visit.
- •Consumes greater than 3 glasses of alcoholic beverages, wine or distilled spirits per day.
- •Consumes excessive amounts of caffeinated beverages per day.
- •Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day.
- •Has a positive urine drug screen (except for cannabis) at screening and/or pre-dose.
- •Has received any investigational agent or any anti-retroviral agent within 60 days of study drug administration; or intends to receive any ART during this study.
研究组 & 干预措施
A: MK-8583 100mg
After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
干预措施: MK-8583 (Drug)
B: MK-8583 ≤ 150 mg
After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments
干预措施: MK-8583 (Drug)
C: MK-8583 ≤ 150 mg
After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments
干预措施: MK-8583 (Drug)
结局指标
主要结局
Number of Participants With at Least One Adverse Event (AE)
时间窗: Up to Day 29
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Number of Participants Who Discontinued Study Due to an AE
时间窗: Day 1
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose.
时间窗: Baseline (pre-dose) and 168 hours post-dose.
Plasma HIV-1 RNA was measured at baseline and 168 hours after dosing. Change from baseline for MK-8583 at 168 hours post-baseline was estimated from longitudinal data analysis (LDA) model containing fixed effects for time (predose, 168 hours postdose) and a random effect for participant. The change from baseline in plasma HIV-1 RNA in participants administered MK-8583 was compared with historical placebo data.
次要结局
- Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP)(Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose)
- Time to Achieve Maximum Concentration (Tmax) of TFV-DP(Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose)
- Maximum Concentration (Cmax) of TFV-DP(Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose)
- Concentration at 168 Hours Postdose (C168hr) of TFV-DP(168 hr postdose)
- Apparent Terminal Half-life (t1/2) of TFV-DP(Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose)
- Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- Area Under the Concentration Time Curve From Time 0-infinity (AUC0-inf) of MK-8583(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- Tmax of Plasma MK-8583.(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- Cmax of MK-8583(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- t1/2 of MK-8583(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- Apparent Total Clearance (CL/F) of MK-8583(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- Apparent Volume of Distribution (Vz/F) of MK-8583(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- AUC0-last of Tenofovir (TFV)(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- AUC0-inf of TFV(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- Tmax of TFV(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- Cmax of TFV(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)
- t1/2 of TFV(Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose)