Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-infected Ugandan Adults
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-Time Curve(AUC)
研究概览
简要总结
The null hypothesis is that there is a difference in the the relative rate and extent of absorption into the systemic circulation of Triomune and brand-name Stavudine/Lamivudine/Nevirapine in HIV-infected Africans and the alternative hypothesis is that there is no difference in the the relative rate and extent of absorption into the systemic circulation of Triomune and brand-name Stavudine/Lamivudine/Nevirapine in HIV-infected Africans. This is a non-inferiority study.
详细描述
Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of Lamivudine, Stavudine and Nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®). An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received Lamivudine (150 mg), Stavudine (40 mg), and Nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC0-12h and Cmax. Bioequivalence was defined as a geometric mean ratio between the generic and brand-name within the 90% confidence interval of 0.8-1.25.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-infected men and non-pregnant women;
- •On Triomune for at least 4 weeks;
- •18 years or greater;
- •Residing within 15km of Kampala city center
排除标准
- •Unable to sign or understand informed consent
- •Concurrent medication known to interact with any of the components of Triomune
- •Patients with active TB, malabsorption, nausea, emesis, abdominal discomfort, chronic diarrhoea, documented active clinically relevant hepatitis;
- •Patients expected to change their drug regimen or dosage during the study
- •Those planning to move out of Kampala in the next two months;
- •Hemoglobin <7.0 mmol/l (men) or <6.5 mmol/l (women);
- •Alanine aminotransferase or aspartate aminotransferase >5 times the upper limit of normal;
- •Serum creatinine > 1.5 times the upper limit of normal
研究组 & 干预措施
Generic
generic fixed dose combination of Stavudine, Lamivudine and Nevirapine (Triomune)
干预措施: Triomune (Drug)
Brand
3 separate single pills of Zerit (Stavudine)Epivir (Lamivudine) Viramune (Nevirapine)
干预措施: Zerit/Epivir/Viramune (Drug)
结局指标
主要结局
Area Under the Concentration-Time Curve(AUC)
时间窗: Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing
Mean Area Under the Plasma Concentration-Time Curve for each drug, log transformed
次要结局
- Maximum Plasma Concentration of Drug(Assessed at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 12 hr post-dosing)