A Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir in Combination With Rifampin in HIV-1-infected Patients With Tuberculosis.
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Proportion of patients with expected pre dose concentration of lopinavir.
研究概览
简要总结
The object of this study is to evaluate the pharmacokinetic interactions, short term safety and efficacy of standard dose lopinavir/ritonavir 200mg/50 (two tablets twice daily) given with ritonavir 100 mg three tablets twice daily given in combination with rifampin in HIV-infected persons with tuberculosis
详细描述
This will be an open label non-randomized pharmacokinetic study of 10-12 HIV-infected patients co-infected with Mycobacterium tuberculosis.
Enrollment: Potential subjects with active tuberculosis who have tolerated a rifampin containing regimen for at least 2 weeks. Potential subjects will be referred from the surrounding communities to Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)
Visit 1: Subjects will then be started on lopinavir/ritonavir containing HAART regimen with standard twice daily dosing. Ritonavir 100 mg capsules will be added to the regimen and the dose escalated until the patient is taking 3 capsules twice daily. The time between enrollment and visit 1 will be determined by the treating physician.
Visit 2: They will return about 1 week after dose escalation has been completed to sample lopinavir and rifampin concentrations.
Visit 3: Subject will return in 2 weeks to have repeat to review results of lopinavir concentrations and response to therapy. Ritonavir will be adjusted as needed.
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
- 未提供
排除标准
- •Non-compliance with DOTPlus. Alternatively DOT can be done by telephoning patient on a daily basis 5 times a week and having patient annotate taking drug in a log which would be reviewed by clinic staff
- •History of being treated for tuberculosis in the prior 2 years unless there is DST, including PCR testing, showing sensitivity to rifamycin.
- •Known hypersensitivity to rifampin or rifabutin.
- •Liver enzymes greater than 2 times ULN.
- •Bilirubin greater than 2 times ULN.
- •Serum creatinine greater than 3 times ULN.
- •Hemoglobin less than 7.0 gms even if receiving erythropoietin.
- •Absolute neutrophil count less than 750 cells/mm3 even if receiving G-CSF.
- •Fasting triglycerides greater than 400 mg/dL.
- •Fasting cholesterol > 1.6 upper limits of normal.
- •GI intolerance of tuberculosis medications requiring discontinuation of tuberculosis medications.
- •Fasting glucose greater 150 mg/dL.
- •Pregnant women.
- •Use of one of the prohibited medications
- •Any condition that the investigators feel could compromise the use of the current medication.
- •Have a CD4 cell count of 50 cells/mm3or less
- •Hepatitis B or C infection
- •Alcohol or illicit drug use, which in the investigators opinion may affect participation in study.
研究组 & 干预措施
Lopinavir/ritonavir and ritonavir
Two tablets of twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 tablets of ritonavir 100 mg of twice daily given with rifampin 600 mg daily.
干预措施: Lopinavir/ritonavir and ritonavir (Drug)
结局指标
主要结局
Proportion of patients with expected pre dose concentration of lopinavir.
时间窗: Weeks 2 and 8: lopinavir time points at hours 0, 2, 4, 6 and 8.
The expected pre dose concentration of lopinavir is \>1.0 mcg/mL.
次要结局
- Proportion of patients with expected AUC of rifampin(Approximatley 10-12 weeks)
- Proportion of patients with expected Cmax of rifampin.(Weeks 2 and 8: rifampin time points at hours 0, 2, 4, 6 and 8.)
- Proportion of patient with success of tuberculosis therapy(Approximatly 10-12 weeks)
- Proportion of patients with successful treatment of HIV therapy.(Approximately 10-12 weeks)
- Proportion of patients with expected Cmax and AUC of lopinavir(10-12 weeks)
研究者
Catherine Boulanger
Associate of Professor of Clinical Medicine
University of Miami