Randomized, Phase I/II, Dose-Ranging, Open-Label Trial of the Anti-HIV Activity of Delavirdine Mesylate (DLV; U-90,152S)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 10
研究概览
简要总结
PRIMARY: To study the safety and tolerance of delavirdine mesylate ( U-90152 ) monotherapy. To compare the anti-HIV activity of three blood concentration levels of this agent with nucleoside analog monotherapy, either zidovudine ( AZT ) or didanosine ( ddI ), based on the reduction of HIV viral burden.
SECONDARY: To use pharmacokinetic parameters to assess the relationship between daily drug exposure and antiviral activity and toxicity of the U-90152, AZT, and ddI monotherapy. To assess anti-HIV activity using other disease markers.
Data suggest that bisheteroarylpiperazines (BHAPs) such as delavirdine mesylate are potent and safe anti-HIV agents and may have different biological behavior than other currently available non-nucleoside RT inhibitors.
详细描述
Data suggest that bisheteroarylpiperazines (BHAPs) such as delavirdine mesylate are potent and safe anti-HIV agents and may have different biological behavior than other currently available non-nucleoside RT inhibitors.
Patients are randomized to receive U-90152 at one of three doses (treatment arms I through III) or either AZT or ddI (treatment arm IV). Patients on arm IV who are AZT-naive receive AZT; those who are AZT-experienced receive ddI. Treatment continues for 24 weeks.
PER 12/22/94 AMENDMENT: All patients receiving U-90152 have the same starting dose, to attain one of three target trough levels.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •Concurrent Medication:
- •PCP prophylaxis.
- •Topical antifungal agents, clotrimazole troches, nystatin oral suspension, topical ketoconazole, and oral fluconazole.
- •Acyclovir (<= 1000 mg/day) as maintenance therapy for herpes simplex virus.
- •Recombinant erythropoietin and G-CSF.
- •Antibiotics for bacterial infections, unless specifically excluded.
- •Symptomatic treatment such as antipyretics, analgesics, nonsteroidal anti-inflammatory agents, and antiemetics.
- •Antacids.
- •Patients must have:
- •HIV-1 infection.
- •CD4 count 200 - 500 cells/mm
- •Either no prior antiretroviral therapy or discontinued AZT monotherapy 3 or more weeks prior to study entry.
- •Half of patients should be antiretroviral naive.
- •Prior Medication:
- •Prior AZT.
排除标准
- •Co-existing Condition:
- •Patients with the following symptoms or conditions are excluded:
- •Malignancy other than minimal Kaposi's sarcoma.
- •Concurrent Medication:
- •Rifabutin.
- •Rifampin.
- •Terfenadine.
- •Astemizole.
- •Loratadine.
- •Trifluoperazine.
- •Piperazine citrate.
- •Any acute or chronic therapy for CMV, MAC, toxoplasmosis, or disseminated fungal infection.
- •Non-study antiretroviral therapies, interferons, biologic response modifiers, and HIV vaccines.
- •Systemic corticosteroids for more than 21 consecutive days.
- •Foscarnet.
- •Systemic cytotoxic chemotherapy for a malignancy.
- •Patients with the following prior conditions are excluded:
- •History of pancreatitis (in patients who received prior AZT).
- •History of grade 2 or worse peripheral neuropathy (in patients who received prior AZT).
- •History of hypersensitivity to BHAP compounds (e.g., trifluoperazine - Stelazine, piperazine citrate - Antepar).
- •Prior Medication:
- •Excluded within 30 days prior to study entry:
- •Any investigational medication.
- •Interferon.
- •Interleukin.
- •Rifabutin.
- •Rifampin.
- •Terfenadine.
- •Astemizole.
- •Loratadine.
- •Trifluoperazine.
- •Piperazine citrate.
- •Excluded at any time:
- •Prior ddI, ddC, d4T, or 3TC.
- •Prior foscarnet.
- •Prior BHAP compound or other non-nucleoside RT inhibitor.
- •Active substance abuse interfering with compliance.