A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiretroviral Activity of MK-1439 in HIV-1 Infected Patients
概览
- 阶段
- 1 期
- 干预措施
- Doravirine
- 疾病 / 适应症
- HIV-1 Infection
- 发起方
- Merck Sharp & Dohme LLC
- 入组人数
- 18
- 主要终点
- Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load
- 状态
- 已完成
- 最后更新
- 7年前
概览
简要总结
This is a study to evaluate the safety, tolerability, pharmacokinetics, and antiretroviral activity of doravirine (MK-1439) as monotherapy in antiretroviral therapy (ART)-naïve, HIV-1-infected participants.
研究者
入排标准
入选标准
- •Diagnosis of HIV-1-infection ≥3 months prior to screening
- •Participants with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
- •Body Mass Index (BMI) ≤35 kg/m\^2
- •Other than HIV infection, participant's baseline health is judged to be stable
- •No clinically significant abnormality on electrocardiogram (ECG)
- •Participant is ART-naïve (defined as having never received any antiretroviral agent or ≤30 consecutive days of an investigational antiretroviral agent (excluding an Non-Nucleoside Reverse Transcriptase Inhibitor \[NNRTI\]) or ≤60 consecutive days of combination ART not including an NNRTI)
- •Participant is willing to receive no other ART for the duration of the treatment phase of this study.
排除标准
- •History of stroke, chronic seizures, or major neurological disorder
- •History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, or genitourinary abnormalities or diseases
- •History of clinically significant neoplastic disease
- •Participant has used any immune therapy agents or immunosuppressive therapy within 1 month prior to treatment in this study
- •Participant has one or more pre-existing risk factors for Torsades de Pointes (New York Heart Association Functional Classification II through IV heart failure, familial long-QT-syndrome, uncorrected hypokalemia, QTcF \>470 msec)
- •Participant requires or is anticipated to require chronic daily prescription medications
- •Current (active) diagnosis of acute hepatitis due to any cause
- •History of chronic Hepatitis C virus (HCV) unless there has been documented cure and/or patient with a positive serologic test for HCV has a negative HCV viral load.
- •Positive Hepatitis B surface antigen
- •Participant is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort \[Hypericum perforatum\]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the post-study visit
研究组 & 干预措施
Panel A: Doravirine 25 mg or Placebo
Participants will receive oral doses of doravirine 25 mg or placebo once daily for 7 days.
干预措施: Doravirine
Panel A: Doravirine 25 mg or Placebo
Participants will receive oral doses of doravirine 25 mg or placebo once daily for 7 days.
干预措施: Placebo
Panel B: Doravirine 200 mg or Placebo
Panel B (doravirine 200 mg or placebo once daily for 7 days) will initiate upon satisfactory review of safety and tolerability from Panel A, and all safety, tolerability and pharmacokinetic data from the study MK-1439-001.
干预措施: Doravirine
Panel B: Doravirine 200 mg or Placebo
Panel B (doravirine 200 mg or placebo once daily for 7 days) will initiate upon satisfactory review of safety and tolerability from Panel A, and all safety, tolerability and pharmacokinetic data from the study MK-1439-001.
干预措施: Placebo
Panel C: Doravirine or Placebo
Panel C is optional. If conducted, the dose will be confirmed after review of data from prior panels.
干预措施: Doravirine
Panel C: Doravirine or Placebo
Panel C is optional. If conducted, the dose will be confirmed after review of data from prior panels.
干预措施: Placebo
结局指标
主要结局
Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load
时间窗: Baseline and Day 7
The change from baseline to Day 7 in plasma HIV RNA viral load was determined for each arm. Results are expressed as change in HIV RNA log10 copies/mL after 7 daily doses of doravirine or placebo. It was hypothesized that at least 1 dose of doravirine would be superior to placebo as documented by the upper bound of the 90% confidence interval \<-1. Plasma HIV RNA levels were determined using the Abbott RealTime HIV assay which has a linear range from 40 to 10 million copies/mL.
次要结局
- Area Under the Plasma Concentration Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of Doravirine on Day 7(Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7)
- Plasma Concentration 24 Hours Postdose (C24hr) of Doravirine on Day 7(24 hours postdose on Day 7 (Day 8))
- Time to Maximum Plasma Concentration (Tmax) of Doravirine on Day 7(Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7)
- Maximum Plasma Concentration (Cmax) of Doravirine on Day 7(Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7)