NCT00035932已完成3 期
Phase III Open Label Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV
Bristol-Myers Squibb0 个研究点目标入组 571 人开始时间: 2001年11月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 571
- 主要终点
- Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24
研究概览
简要总结
The purpose of this study is to learn how well atazanavir (ATV) works in combination with ritonavir (RTV) or saquinavir (SQV) with tenofovir (TDF) and a nucleoside to reduce the viral load of treatment experienced subjects with human immunodeficiency virus (HIV). There is a comparison arm with lopinavir (LPV)/RTV and TDF and a nucleoside.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Virologic failure to 2 or more highly active antiretroviral therapy (HAART) regimens that, in total, have included at least one drug from all approved classes protease inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (PI, NNRTI, NRTI):
- •Currently on a failing HAART regimen with 2 qualifying plasma viral load measurements (hospital/clinic value within 4 weeks of screening with viral load equivalent to =>1,000 c/mL on the Roche Amplicor[TM] and central lab measurements of =>1,000 c/mL (Roche Amplicor[TM]) within 4 weeks of randomization
- •Cluster of Differentiation 4 (CD4) cell count =>50 cells/mm3 obtained within 4 weeks prior to randomization
- •=>16 years of age (or minimum age as determined by local regulations or as legal requirements dictate);
- •History of prior virologic response to at least one HAART regimen, defined as a 1.0 log10 decline or a decline in viral load to <400 c/mL by Roche Amplicor or <500 c/mL by Chiron Quantiplex branched DNA (bDNA) assay
- •Both females of child bearing potential and males must utilize effective barrier contraception to reduce transmission of sexually transmitted disease, including human immunodeficiency virus (HIV). Other contraception in addition to barrier methods is permitted; interaction between atazanavir and oral contraceptives has not been studied.
- •Subjects must be able to provide written informed consent;
- •Subjects should be available for follow-up for a period of at least 48 weeks
- •Baseline laboratory values measured within 2 weeks prior to initiating study drugs as follows:
- •serum creatine <1.5 times the upper limit of normal (ULN)
- •total serum lipase <1.4 times the ULN
- •liver enzymes alanine aminotransferase (AST), aspartate aminotransferase (ALT) <3 times the ULN
- •total serum bilirubin <1.5 times the ULN
排除标准
- •Prior use (=>3 days) of atazanavir, TVF or LPV/RTV; if history of SQV, then must be phenotypically sensitive
- •the current failing antiretroviral regimen must have been administered for at least eight weeks at he initiation of screening and must not include both a PI and NNRTI
- •Presence of a newly diagnosed HIV-related opportunistic infection or any medical requiring acute therapy at the time of enrollment
- •Proven or suspected acute hepatitis in the 30 days prior to study entry. Subjects with chronic hepatitis are eligible provided that their liver function enzymes (ALT/AST) are <3 x ULN
- •Previous therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatoxic, hepatoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment of therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect Cytochrome P450 3A4 (CYP3A4).
- •Active alcohol or substance use sufficient, in the Investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis
- •Intractable diarrhea (=> 6 loose stools/day for at least 7 days consecutive days) within 30 days prior to study entry
- •Pregnancy or breast-feeding
- •History of hemophilia
- •Presence of cardiomyopathy
- •Any one of the following:
- •Heart rate-corrected QT (QTc) interval >450 msec on the screening electrocardiogram (EKG)
- •Heart rate <40 beats per minute (bpm)
- •Pause length >3 seconds seen on EKG
- •Clinical symptoms potentially related to heart block
- •Third degree heart block
- •History of acute or chronic pancreatitis
- •If choosing 2'-3' dideoxyinosine (ddI) or 2',3'-didehydro-3'-deoxythymidine (d4T) as the NRTI: History or signs and symptoms of bilateral peripheral neuropathy => Grade 2 at the time of screening
- •Inability to tolerate oral medications
- •Any other clinical conditions or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for study or unable to comply with the dosing requirements.
研究组 & 干预措施
I
Active Comparator
ATV 300 mg + RTV 100 mg + TDF 300 mg + nucleoside of choice
ATV , RTV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study
干预措施: Atazanavir + ritonavir + tenofovir + nucleoside (Drug)
II
Active Comparator
ATV 400 mg + SQV 1200 mg + TDF 300 mg + nucleoside of choice
ATV, SQV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study
干预措施: Atazanavir + saquinavir + tenofovir + nucleoside (Drug)
III
Active Comparator
LPV/RTV 400/100 mg + TDF 300 mg + nucleoside of choice
LPV/RTV twice daily, TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study
干预措施: Lopinavir/ritonavir + tenofovir + nucleoside (Drug)
结局指标
主要结局
Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24
时间窗: Baseline, Week 24
Mean Change From Baseline in HIV RNA at Week 48
时间窗: Baseline, Week 48
Mean Change From Baseline in HIV RNA at Week 96
时间窗: Baseline, Week 96
次要结局
- Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity)(Baseline, Week 48)
- Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96(Baseline, Week 96)
- Mean Change From Baseline in HIV RNA at Week 2(Baseline, Week 2)
- Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity)(Baseline, Week 24)
- Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24(Week 24)
- Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24, by PI Sensitivity(Baseline, Week 24)
- Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48(Week 48)
- Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48, by PI Sensitivity(Baseline, Week 48)
- Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96(Week 96)
- Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24(Week 24)
- Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48(Week 48)
- Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96(Week 96)
- Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24(Week 24)
- Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48(Week 48)
- Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96(Week 96)
- Change From Baseline in CD4 Cell Count at Week 24(Baseline, Week 24)
- Change From Baseline in CD4 Cell Count at Week 48(Baseline, Week 48)
- Change From Baseline in CD4 Cell Count at Week 96(Baseline, Week 96)
- Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24(Baseline, Week 24)
- Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 48(Baseline, Week 48)
- Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24(Baseline, Week 24)
- Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 48(Baseline, Week 48)
- Lipid Mean Percent Change From Baseline at Week 24(Baseline, Week 24)
- Lipid Mean Percent Change From Baseline at Week 48(Week 48)
- Lipid Mean Percent Change From Baseline at Week 96, Observed Values(Week 96)
- Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48(From Enrollment through Week 48)
- Most Common AEs and AEs of Interest Through Week 48(From Enrollment to Week 48)
- Fasting Glucose Mean Change From Baseline at Week 24(Baseline, Week 24)
- Fasting Glucose Mean Change From Baseline at Week 48(Week 48)
- Grade 3/4 Laboratory Abnormalities Through Week 48(From Enrollment to Week 48)
- Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point(Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48)
- PR Interval and Change From Baseline by Analysis Time Point(Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48)
- Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire(Baseline, Week 24, Week 48)
- Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48)(Baseline, Week 24, Week 48)
- Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48)(Baseline, Week 24, Week 48)
- Number of Participants Utilizing Resources for Managing Lipid Elevation(Baseline, Week 24, Week 48)
- Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values(collected at the pre-dose time point after receiving atazanavir for at least four weeks)
- HIV IC50 at Week 24(Week 24)
- Inhibitory Quotient at Week 24(Baseline, Week 24)
- Inhibitory Quotient at Week 48(Baseline, Week 48)
- HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24(Baseline, Week 24)
- HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 48(Baseline, Week 48)
研究者
相似试验
已完成
4 期
Study of Boosted Atazanavir (ATV) Versus Non-boosted ATV in Naive PatientsHIV InfectionsNCT00084253Bristol-Myers Squibb200
已完成
4 期
Nevirapine vs. Atazanavir Boosted With Ritonavir on a Background of Truvada in Human Immunodeficiency Virus (HIV) Infected Naive Patients (NEwArT)HIV InfectionsNCT00552240Boehringer Ingelheim154
已完成
3 期
PRINCE: Study of Atazanavir (ATV)/Ritonavir (RTV)HIV InfectionsNCT01099579Bristol-Myers Squibb82
已完成
1 期
Dose Finding Confirmation of Atazanavir With Ritonavir and Efavirenz (ATV/RTV + EFV) in Healthy SubjectsProtease InhibitorHIV InfectionsNCT00357188Bristol-Myers Squibb22
已完成
3 期
Phase IIIb Study to Evaluate the Effectiveness and Safety of Atazanavir/Ritonavir as Single Enhanced Protease Inhibitor Therapy in Human Immunodeficiency Virus (HIV)-Infected Subjects Evidencing Virologic SuppressionHuman Immunodeficiency Virus (HIV) InfectionsNCT00337467Bristol-Myers Squibb61