A Phase IIa, Randomized, Double-blind, Active-controlled, 12-week Study of Amdoxovir (Two Doses) Versus Tenofovir DF, in Combination With Zidovudine in HIV-1 Treatment-experienced Subjects With M184I/V Mutation in Addition to 0-2 Confirmed Thymidine Analog Mutations.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- HIV-1 viral load
研究概览
简要总结
This is a double-blind Phase 2a study to test the safety and efficacy of an investigational HIV drug, amdoxovir (300 mg or 500 mg twice daily) compared with tenofovir DF 300 mg once daily in HIV-1 infected antiretroviral therapy-experienced subjects who are currently failing antiretroviral therapy. There are three treatment groups (N=45). Subjects will be randomized to receive either amdoxovir 300 mg twice daily (n=15) or amdoxovir 500 mg twice daily (n=15) or tenofovir DF 300 mg once daily (n=15); each in combination with zidovudine 300 mg twice daily.
The study will assess initially amdoxovir (300 mg or 500 mg twice daily) or tenofovir DF 300 mg once daily, both in combination zidovudine 300 mg twice daily plus failing third drug, but then with lopinavir/ritonavir (400 mg/100 mg twice daily) after Week 2. Subjects who received amdoxovir (300 mg or 500 mg twice daily) and benefited from the drug may choose to enroll in the 36-week open-label study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Male or female ≥ 18 years old with HIV-1 RNA ≥ 2,000 copies/mL and currently failing therapy.
- •Has M184I/V mutation in addition to 0-2 thymidine analog mutations (TAMs) at screening.
- •Agree to be abstinent or use two reliable forms of contraception (for females) and one form for men when participating in sexual activity that could result in pregnancy.
排除标准
- •Current or recent (last 30 days of study entry) AIDS defining diseases.
- •Genotypic resistance testing at screening indicating K65R, L74V, Q151M mutation.
- •Prior exposure to lopinavir/ritonavir or amdoxovir.
- •Impaired hepatic function (ALT > 5 x ULN).
- •Women who are pregnant or breast feeding.
研究组 & 干预措施
amdoxovir 300 mg bid
in combination with zidovudine 300 mg bid for 12 weeks; lopinavir/ritonavir (400 mg/100 mg) bid is added on week 3
干预措施: amdoxovir 300 mg bid (Drug)
amdoxovir 500 mg bid
in combination with zidovudine 300 mg bid for 12 weeks; lopinavir/ritonavir (400 mg/100 mg) bid is added on week 3
干预措施: amdoxovir 500 mg bid (Drug)
tenofovir DF 300 mg qd
in combination with zidovudine 300 mg bid for 12 weeks; lopinavir/ritonavir (400 mg/100 mg) bid is added on week 3
干预措施: tenofovir DF 300 mg qd (Drug)
结局指标
主要结局
HIV-1 viral load
时间窗: change from baseline to Week 2
Safety and Tolerability- Incidence of adverse events and laboratory abnormalities
时间窗: number and frequency from baseline through Week 12
次要结局
- HIV-1 viral load(change from baseline to Weeks 4, 8 and 12)
- Changes in Immunologic Function (CD4 cell counts)(changes from baseline to Weeks 4, 8 and 12)