The Penetration of Maraviroc Into the Central Nervous System in HIV-1 Infected Subjects on Stable Antiretroviral Therapy; a Phase I Pharmacokinetic Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- CSF (Cerebrospinal Fluid) : Plasma Ratio of Maraviroc 1H Magnetic Resonance Spectroscopy (1H-MRS)
研究概览
简要总结
The purpose of this study is to describe the Central Nervous System exposure of maraviroc in HIV-1 infected subjects receiving a stable antiretroviral regimen, including maraviroc, at steady state.
详细描述
15 HIV-1 infected subjects currently receiving stable antiretroviral therapy will be recruited. At study entry, within 14 days of screening procedures, subjects will commence maraviroc dosed at 150 mg twice daily. For the rest of study period antiretroviral therapy will comprise:
- Truvada™ one tablet once daily at 0900
- Kaletra™ two tablets twice daily 0900 and 2100
- maraviroc 150 mg twice daily at 0900 and 2100
Subjects will attend for regular clinic visits during study treatment phase.
On day 15, subjects will attend the unit in the morning prior to usual dosing time. Blood with be drawn to assess plasma maraviroc concentration pre dose and pre lumbar puncture. A lumbar puncture will be performed under standard aseptic techniques to asses CSF maraviroc concentration and routine CSF parameters.
On completion of this study visit, subjects will cease maraviroc, continue on their usual antiretroviral regimen and attend for a follow up visit 10 days later.
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
- 否
入选标准
- •HIV-1 infected males or females
- •signed informed consent
- •plasma HIV RNA < 50 copies/mL at screening and on at least one other occasion over the last 3 months
- •currently receiving a stable antiretroviral regimen comprising of:
- •tenofovir 245 mg daily
- •emtricitabine 200 mg daily
- •a boosted protease inhibitor
- •no previous protease inhibitor resistance documented on HIV-1 genotypic resistance testing
- •Between 18 to 65 years of age, inclusive
- •subjects in good health upon medical history, physical exam, and laboratory testing
- •Female subjects who are heterosexually active and of childbearing potential (i.e., not surgically sterile or at least two years post menopausal) must practice contraception as follows from screening through completion of the study including 30 days following last dose of study drug:
- •barrier contraceptives (condom, diaphragm with spermicide)
- •IUD PLUS a barrier contraceptive
- •Female subjects of childbearing potential must have a negative pregnancy test.
- •Male subjects who are heterosexually active must use two forms of barrier contraception (e.g., condom with spermicide) during heterosexual intercourse, from screening through completion of the study including 30 days following last dose of study drug.
- •Have no serologic evidence of active HBV infection evidenced by negative hepatitis B surface antigen and no serologic evidence of hepatitis C virus infection by a HCV antibody or HCV PCR.
- •Have screening laboratory results (haematology, chemistry, and urinalysis) that fall within the normal range of the central laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance
排除标准
- •current alcohol abuse or drug dependence
- •active opportunistic infection or significant co-morbidities including dementia
- •current prohibited concomitant medication (as listed in section 4.1.4)
- •Have a body mass index (BMI) > 32
- •Contraindication to lumbar puncture examination. Such as:
- •Existing neurological diseases
- •Bleeding disorders
研究组 & 干预措施
Maraviroc
干预措施: Maraviroc (Drug)
结局指标
主要结局
CSF (Cerebrospinal Fluid) : Plasma Ratio of Maraviroc 1H Magnetic Resonance Spectroscopy (1H-MRS)
时间窗: 15 days
To describe the CNS exposure of maraviroc in HIV-1 infected subjects receiving a stable antiretroviral regimen, including maraviroc, at steady state. It were assessed by in vivo cerebral (1)H magnetic resonance spectroscopy ((1)H-MRS). Cerebral MRS imaging (T1- and T2-weighted images) was performed on a Phillips Achieva™ 1.5 Tesla magnetic resonance (MR) scanner (Phillips NV, Best, Netherlands) and studied by an experienced neuroradiologist
次要结局
- Number of Participants With Adverse Events(15 days)
研究者
Alan Winston
Reader and Honorary HIV consultant
Imperial College London