A Phase 1, Open-Label, Fixed-Sequence, Drug Interaction Study to Investigate the Effect of Once-Weekly Rifapentine and Isoniazid on the Pharmacokinetics of Steady-State Doravirine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Doravirine Maximum Concentration (Cmax)
研究概览
简要总结
Drug therapy for persons living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) co-infected with latent tuberculosis infection (LTBI) is complex. Anti-tuberculosis drugs used to treat LTBI often induce drug metabolizing enzymes that share the same metabolic pathway as antiretroviral drugs used for those living with HIV/AIDS. This study evaluates the drug-drug interaction (DDI) potential of an antiretroviral drug when co-administered with a common anti-tuberculosis regimen of drugs.
详细描述
Rifapentine (RPT) and isoniazid (INH) given once weekly for 12 weeks is commonly used for treating LTBI in adults. For people living with HIV-1, the risks of LTBI is increased. Individuals living with HIV-1 are often on chronic antiretroviral drugs that prevent immunodeficiency and complications associated with infection. Unfortunately, antiretroviral drugs are subject to many DDIs especially with RPT which induces drug clearing enzymes.
Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection. Because RPT induces the metabolic pathway in which DOR is removed, there is concern that taking both concomitantly will result in an unwanted DDI leading to reduced DOR concentrations in the blood. Reduced levels will result in loss of efficacy for the drug and therefore not provide adequate viral suppression in those living with HIV. This study investigates the DDI potential of the once weekly regimen RPT and INH together with DOR in healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 是
入选标准
- •Healthy male or female between 18-60 years old at the time of screening.
- •Have a Body Mass Index (BMI) > 19 and <
- •Weigh > 45 kg but < 120 kg.
- •Non-smoker (tobacco or electronic cigarettes).
- •Negative QuantiFERON-TB Gold at screening.
- •Subjects who agree to abstain from alcohol consumption throughout the duration of the study.
- •Female subjects of childbearing potential must demonstrate a urine beta-hCG consistent with non-pregnancy at the time of the screening visit and agree to the use (and/or have their partner use) of an acceptable method of birth-control at initial screening, during the time of the trial and until two weeks after the last dose of drug following the last treatment period.
- •Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
排除标准
- •History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, dermatologic, psychiatric abnormalities or neurological (including stroke and chronic seizure) diseases.
- •>500 mL blood or plasma donation in the 6 weeks prior to study start
- •Known anaphylactic or severe systemic reactions to any components of doravirine, rifapentine, isoniazid or pyridoxine.
- •Positive HIV, Hepatitis B or Hepatitis C virus. Evidence of prior Hepatitis B infection and immunity is not exclusionary.
- •Latent or active tuberculosis infection. Documented prior fully treated latent tuberculosis is not exclusionary.
- •Females who are postpartum < 12 months.
- •Current drug or alcohol abuse.
- •Received study drug in another study within 4 weeks or within 5 half-lives, which ever occurring first, before first anticipated dose of study drug in this study.
- •Unable to refrain from use of over-the-counter, prescription (unless determined appropriate by the investigator), herbal or natural products, vitamins or supplements, or grapefruit juice/grapefruit products.
- •Any clinical significant findings on lab, ECG or physical exam at screening.
研究组 & 干预措施
Experimental
Period 1: DOR twice-daily alone (Study days 1-4) and Period 2: DOR twice-daily with RPT and INH once-weekly (Study days 7-21)
干预措施: Doravirine (DOR) (Drug)
Experimental
Period 1: DOR twice-daily alone (Study days 1-4) and Period 2: DOR twice-daily with RPT and INH once-weekly (Study days 7-21)
干预措施: Rifapentine (RPT) (Drug)
Experimental
Period 1: DOR twice-daily alone (Study days 1-4) and Period 2: DOR twice-daily with RPT and INH once-weekly (Study days 7-21)
干预措施: Isoniazid (INH) (Drug)
结局指标
主要结局
Doravirine Maximum Concentration (Cmax)
时间窗: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Doravirine maximum observed concentration during the dosing interval
Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12)
时间窗: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Doravirine area under the plasma-concentration time curve derived from plasma sampling during one dosing interval
Doravirine Oral Clearance (CL/F)
时间窗: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Doravirine apparent oral clearance derived from plasma sampling
次要结局
- Adverse Event(Days 1-24 post-dose (period 1 and 2) and 31-34 post-dose (post-study))
研究者
Walter K. Kraft
Principal Investigator
Thomas Jefferson University