A Pilot Study of the Pharmacokinetics and Safety of Rifabutin 150 mg Once Daily Versus Rifabutin 300 mg Thrice Weekly With Lopinavir/Ritonavir Based HAART in HIV/TB Co-infected Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- pharmacokinetics of rifabutin Cmax
研究概览
简要总结
To describe the pharmacokinetics of rifabutin 150 mg once daily versus rifabutin 300 mg thrice weekly in combination with LPV/r 400/100mg based HAART in HIV/TB infected patients
详细描述
The overall aim of the project is to evaluate rifabutin as a replacement for rifampicin, for the combined treatment of tuberculosis and HIV infection. Rifabutin represents an alternative to rifampicin for HIV infected patients as its half-life is longer and the enzymatic induction effect appears to be less important on the associated ART drugs. This phase II trial is to determine precisely the pharmacokinetics parameters of rifabutin in combination with LPV/r regimens in Thai HIV/TB infected patients, in order to define optimal doses that will be further tested in a larger phase III trial comparing safety, tolerability and efficacy of rifabutin and rifampicin regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Confirmed HIV positive after voluntary counseling and testing
- •Aged >18-60years of age
- •PI-naïve (NNRTI intolerance/failure) or PI experience ( TB developed during on salvage regimen) without prior PI mutation
- •Any CD4 cell count
- •ALT <5 times ULN
- •Serum creatinine <1.4 mg/dl
- •Hemaglobin >7 mg/L
- •TB is diagnosed and planned to receive stable doses of rifabutin containing anti-TB therapy for at least another 4 week period after initiation of ART
- •No other active OI (CDC class C event), except oral candidiasis or disseminated MAC
- •Body weight >40kg
- •Able to provide written informed consent
排除标准
- •Current use of steroid (except short course steroid for IRIS) and other immunosuppressive agents.
- •Current use of any prohibited medications related to drug pharmacokinetics.
- •Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the trial.
- •Unlikely to be able to remain in follow-up for the protocol defined period.
- •Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.
- •Karnofsky performance score <30%
- •TB meningitis and bone/joints ( due to longer period of anti TB drug)
- •Patient choose to use efavirenz, not LPV/r. However, in ART naïve, EFV is allowed after intensive PK of LPV/r and rifabutin at week 2-4.
研究组 & 干预措施
rifabutin 150
rifabutin 150 mg (1 capsule) once daily
干预措施: Lopinavir/r will be supplied by NHSO/GPO (Drug)
rifabutin 150
rifabutin 150 mg (1 capsule) once daily
干预措施: Rifabutin (Drug)
rifabutin 300
rifabutin 150 mg (2 capsules) 300 mg 3 times a week
干预措施: Lopinavir/r will be supplied by NHSO/GPO (Drug)
rifabutin 300
rifabutin 150 mg (2 capsules) 300 mg 3 times a week
干预措施: Rifabutin (Drug)
结局指标
主要结局
pharmacokinetics of rifabutin Cmax
时间窗: 48 weeks
Cmax The peak plasma concentration of rifabutin after administration
次要结局
- adverse events(48 weeks)
- viral load(48 weeks)
- CD4(48 weeks)
- Monodrug resistant TB(48 weeks)
- death(48 weeks)
- AIDS event(48 weeks)
- TB cure(48 weeks)
- TB relapse(48 weeks)
- Multidrug-resistant TB (MDR TB)(48 weeks)
- TB treatment failure(48 weeks)
- Extensively drug resistant TB (XDR TB)(48 weeks)
- weight gain(48 weeks)
- defervescence(48 weeks)
- Karnofsky score(48 weeks)