A Randomized, Open-label Trial to Compare the Efficacy, Safety and Tolerability of DRV/Rtv (800mg/100mg) q.d Versus DRV/Rtv (600mg/100mg) b.i.d in Early Treatment-experienced HIV-1 Infected Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 590
- 主要终点
- Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
研究概览
简要总结
The purpose of this study is to test if being treated with darunavir/ritonavir (DRV/rtv) 800/100 mg daily is as effective as being treated with DRV/rtv 600/100 mg twice daily, in early antiretroviral (ARV)-experienced patients when given along with selected optimized background regimen (OBR).
详细描述
This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention) study in which 590 patients will be randomly assigned to receive either DRV/rtv 800/100 mg daily or DRV/rtv 600/100 mg twice daily along with the selected OBR. An OBR will consist of at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) selected by the investigator. The study will include a 4 week screening period, 48-weeks of treatment period and 4-weeks of follow-up. The study will also consists of extension phase after Week 48: in regions where DRV is not yet commercially available or reimbursed by the health care system, patients who complete the 48 weeks of treatment with DRV/rtv and who continue to benefit from this treatment, will have the opportunity to continue DRV treatment as a 600 mg twice daily dosage until DRV is reimbursed and available via the public and/or private health care system or until its development is discontinued. Safety evaluation will consists of adverse events (including specific toxicities), clinical laboratory tests, vital signs, electrocardiogram, physical and skin examination.
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
- 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
- •Patients with documented human immunodeficiency virus - Type 1 (HIV-1) infection
- •Patients with a viral load greater than 1,000 HIV-1 ribonucleic acid (RNA) copies/mL
- •Stable highly active antiretroviral therapy (HAART) regimen for at least 12 weeks at screening
- •In the investigator's opinion, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are not a valid treatment option, because of the patient's antiretroviral (ARV) treatment history, ARV resistance testing, medication-taking behavior, safety and tolerability concerns, or other patient-related factors
- •Prescreening or/and screening plasma HIV-1 RNA greater than 1,000 copies/mL on HAART regimen at screening
排除标准
- •Presence of any currently active conditions that fit the definition of the World Health Organization (WHO) Clinical Stage 4, with the following exceptions: stable cutaneous kaposi's sarcoma (ie, no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study time period, wasting syndrome
- •Patients for whom an investigational ARV is part of the current regimen, with the following exceptions if applicable (depending on local regulatory approval): tenofovir, emtricitabine
- •Previous or current use of enfuvirtide (ENF), tipranavir and/or DRV
- •Life expectancy of less than 12 months
- •Pregnant or breast-feeding females
- •Any active clinically significant disease (eg, tuberculosis [TB], cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the patient's safety or outcome of the study
研究组 & 干预措施
DRV/rtv 800/100 mg once daily
Two 400 mg darunavir (DRV) ie, TMC114 tablets + one 100 mg ritonavir (rtv) capsule once daily.
干预措施: Darunavir (DRV) (Drug)
DRV/rtv 800/100 mg once daily
Two 400 mg darunavir (DRV) ie, TMC114 tablets + one 100 mg ritonavir (rtv) capsule once daily.
干预措施: Ritonavir (rtv) (Drug)
DRV/rtv 600/100 mg twice daily
One 600 mg TMC114 tablet + one 100 mg capsule of rtv twice daily.
干预措施: Darunavir (DRV) (Drug)
DRV/rtv 600/100 mg twice daily
One 600 mg TMC114 tablet + one 100 mg capsule of rtv twice daily.
干预措施: Ritonavir (rtv) (Drug)
结局指标
主要结局
Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
时间窗: 48 Weeks
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
次要结局
- Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL)(48 weeks)
- Change in log10 Viral Load From Baseline at Week 48(48 weeks)
- Time to Reach First Virologic Response(48 weeks)
- Time to Loss of Virologic Response(48 weeks)
- Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks(48 weeks)
- Change in CD4+ Cell Count From Baseline(48 Weeks)
- Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score(48 weeks)
- Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48(48 weeks)
- Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv(0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48.)
- Predose Plasma Concentration (C0h) of DRV and Rtv.(0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48)
- Number of Participants Developing Mutations at Endpoint(48 weeks)