A Pharmacokinetic Study to Evaluate the Interaction Between Nevirapine (Viramune®) and Methadone in HIV-1 Infected, Opioid-dependent Adults on Stable Methadone Maintenance Therapy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Clearance of methadone at steady state in the presence and absence of nevirapine.
研究概览
简要总结
The purpose of this study was to determine the effects of nevirapine treatment on the pharmacokinetics of methadone in HIV-1 infected, opioid-dependent adults who had been on a stable methadone maintenance therapy for at least five days prior to study entry.
详细描述
Ten HIV-1 infected, opioid-dependent adults on stable methadone treatment were to be enrolled in this study. This was an open-label, sequential treatment study, with methadone pharmacokinetics sampling before and after twenty-one (21) days of nevirapine administration.
All patients received the same regimen. Methadone was administered in the first treatment period, and combination treatment of methadone and nevirapine was given in the second treatment period. In the first period, patients received methadone at their current steady state dose. In the second period (study days 1-21), they also received nevirapine 200mg qd (study days 1 to 14) and 200mg bid (study days 15 to 21). Blood samples were taken at the start of the first treatment period and at the end of the second treatment period for analysis of methadone and nevirapine pharmacokinetics parameters.
Study Hypothesis:
It was expected that nevirapine would decrease methadone levels in this patient population.
Comparison(s):
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Treatment-naïve, fulfilling standard criteria to commence antiretroviral therapy. Previous exposure to less than two weeks of nucleoside reverse transcriptase therapy was permitted. (Later amended to allow previous exposure to non-nucleoside reverse transcriptase inhibitor therapy (NNRTI) if the patient was off NNRTI therapy for at least two weeks prior to entry.)
- •Plasma HIV-1 ribonucleic acid (RNA) assay performed at screening documenting HIV-1 infection or previous laboratory documentation of HIV-1 positive status.
- •CD4+ cell count at least 100 cells/mm3 (later amended to at least 50 cells/mm3), within 28 days prior to study day
- •Patients who met the following laboratory parameters:
- •Lymphocyte count at least 1 x 109/L
- •Haemoglobin at least 5.7 mmol/L [9.0 g/dL] (men and women)
- •Platelet count at least 75 x 109/L
- •Alkaline phosphatase less than or equal to 3 times the upper limit of normal
- •Serum glutamate oxaloacetate transferase (SGOT) and serum pyruvate oxaloacetate transferase (SGPT) less than or equal to 3 times the upper limit of normal
- •Total bilirubin less than or equal to 1.5 times the upper limit of normal
- •Serum creatinine less than or equal to 2.0 mg/dL.
- •On stable methadone maintenance therapy for at least five days prior to entry.
- •Patients of reproductive potential must have been willing to use a reliable method of double-barrier contraception (such as a diaphragm with spermicidal cream or jelly, or condoms with spermicidal foam).
- •Informed of, and willing and able to comply with the investigational nature of the study, and have signed a written consent in accordance with ethics committee and regulatory guidelines.
排除标准
- •Female patients who were pregnant or breast-feeding.
- •Systemic treatment with corticosteroids or drugs known to be hepatic enzyme inducers or inhibitors within 14 days of study entry. Substances in these categories include macrolide antibiotics (e.g. erythromycin, clarithromycin), azole antifungals (e.g. ketoconazole, fluconazole, itraconazole), rifampin, rifabutin, and phenytoin.
- •Treatment with any investigational drug within 30 days of the first dose of study medication, and any neoplastic agent or radiotherapy other than local skin radiotherapy treatment within 12 weeks before starting study medication.
- •Malabsorption, severe chronic diarrhoea or unable to maintain adequate oral intake.
- •Treatment for an active infection (secondary to HIV-1).
- •Hepatic insufficiency due to cirrhosis.
- •Renal insufficiency.
- •Excessive alcohol intake.
- •Treatment with ritonavir.
- •Treatment with protease inhibitors.
结局指标
主要结局
Clearance of methadone at steady state in the presence and absence of nevirapine.
次要结局
- Pharmacokinetics of methadone at steady state in the presence and absence of nevirapine