Pharmacokinetics of Tenofovir and Tenofovir-diphosphate, Emtricitabine and Emtricitabine-triphosphate, and Efavirenz Once Daily Over 10 Days Following Drug Intake Cessation in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- pharmacokinetics of plasma tenofovir, emtricitabine and efavirenz
研究概览
简要总结
The purpose of the study is to look at the levels of three HIV medications: tenofovir, emtricitabine, and efavirenz in blood after the drug intake has been stopped in order to understand how long these drugs persist in the blood. The study will specifically look at blood levels of these three drugs (taken as a 3-in-1 tablet) after taking them every day for 14 days.
This study is not randomised which means that all subjects will receive all study medications in the same order. You and the study doctor will know which study medications you are taking at all times during the study.
详细描述
The administration of combination antiretroviral therapy (cART) to HIV-infected patients has been associated with a dramatic reduction in AIDS-related morbidity and mortality [1-3].
The key to successful HIV drug treatment is adhering to the prescribed combination every day [2]. The approval of Atripla® (tenofovir/emtricitabine/efavirenz co-formulated in a single tablet) provides HIV care providers with a "one tablet once a day" therapy, making adherence much easier for patients.
However, in HIV therapy, successful adherence also means attention to intervals between doses or dietary restrictions. Ideally, to guarantee long-term virological response, HIV-infected patients should take their cART every day at the same time. However, cART is for life and doses can be forgotten or delayed.
Importantly, the 24-week 'Five-on-Two-off' (FOTO) study results were presented in November 2008; these showed that when HIV-infected patients stable (viral load < 50 copies/mL) on Atripla® were randomised to continue treatment daily or to stop taking it at weekends, no difference in maintenance of undetectable viral load was observed. Eighty percent in the control arm and 83% in the 'weekend off' arm had a viral load < 50 copies/mL [4]. This suggests that either the drugs' effects, or the drugs themselves, persist for a significant time following drug intake cessation. However, the persistence time and the inter-individual variability of this parameter for the components of Atripla® have not been clearly defined.
A drug's persistence in plasma or in cells depends on its half life. Long half-life antiretroviral agents may allow for missed or delayed doses, if concentrations are maintained at therapeutic levels until the next dose is taken. NRTI are pro-drugs and must be activated by different phosphorilation steps to be effective against HIV. Intracellular triphosphate (TP) metabolites have been shown to be characterized by long half lives. However, data on drug persistence are limited and whether drug doses can be omitted and dosing delayed is unknown.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects must meet all of the following inclusion criteria within 28 days prior to the baseline visit:
- •The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
- •Male or non-pregnant, non-lactating females
- •Between 18 to 65 years, inclusive
- •Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
- •Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 12 weeks after the study
- •Willing to consent to their personal details being entered onto The Over volunteering Prevention Scheme (TOPS) database
- •Willing to provide photographic identification at each visit.
- •Registered with a GP in the UK
排除标准
- •Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
- •Any significant acute or chronic medical illness
- •Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
- •Positive blood screen for hepatitis B surface antigen and/or C antibodies
- •Positive blood screen for HIV-1 and/or 2 antibodies
- •Current or recent (within 3 months) gastrointestinal disease
- •Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
- •Exposure to any investigational drug or placebo within 3 months of first dose of study drug
- •Use of any other drugs (unless approved by the Investigator), including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
- •Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 12 weeks after the end of the treatment period
- •Previous allergy to any of the constituents of the pharmaceuticals administered in this trial
研究组 & 干预措施
All Subjects
All Subjects will receive the same intervention
干预措施: Atripla® (Drug)
结局指标
主要结局
pharmacokinetics of plasma tenofovir, emtricitabine and efavirenz
时间窗: 24 days
To assess the pharmacokinetics of plasma tenofovir and emtricitabine, and their active intracellular anabolites, tenofovir-diphosphate and emtricitabine-triphosphate, and plasma efavirenz over 10 days following drug intake cessation, in HIV negative healthy volunteers
次要结局
- inter subject variability(24 days)
- safety and tolerability of Atripla®(24 days)
- pharmacogenetic(24 days)