A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group Study to Compare the Efficacy and Safety of GW873140 400mg BID in Combination With a Ritonavir-containing Optimized Background Therapy (OBT) Regimen Versus Placebo Plus OBT Over 48 Weeks.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants With Plasma HIV-1 RNA <400 Copies Per Milliliter (Copies /mL) at Week 24 and 48
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of the CCR5 antagonist GW873140 or placebo in combination with an optimized background regimen in treatment-experienced HIV-infected subjects with R5-tropic virus
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •HIV-infected.
- •Screening viral load at least 5000copies/mL.
- •R5-tropic only virus at screening.
- •Total prior antiretroviral experience of at least 3 months and documented resistance to at least one drug in each of the following classes: nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI).
- •Stable antiretroviral regimen (or no antiretroviral treatment) for at least 4 weeks before screening.
- •Able to receive a ritonavir-boosted protease inhibitor during treatment studies.
- •Women of childbearing potential must use specific forms of contraception.
- •Exclusion criteria:
- •Acute laboratory abnormalities.
- •History of pancreatitis or hepatitis, hepatitis B or hepatitis C coinfection, or any chronic liver disease. Screening liver function tests will be used to determine eligibility.
- •R5/X4-tropic, X4-tropic only, or non-phenotypeable virus at screening.
- •Changes to antiretroviral therapy from 4 weeks prior to screening until Day 1 of treatment study.
- •Pregnancy or breastfeeding women.
- •Recent participation in an experimental drug trial.
- •Prior use of a CCR5 or CXCR4 antagonist.
- •Significant ECG abnormalities or significant history of active pancreatitis, hepatitis, opportunistic infections, malabsorption disorders, cancer, or severe illness.
- •Current use of certain medications may exclude participation in this study.
- •Additional qualifying criteria and laboratory test requirements to be assessed by study physician.
排除标准
- 未提供
研究组 & 干预措施
GW873140
干预措施: GW873140 (Drug)
结局指标
主要结局
Number of Participants With Plasma HIV-1 RNA <400 Copies Per Milliliter (Copies /mL) at Week 24 and 48
时间窗: Week 24
Assessment for plasma HIV-1 RNA was done at Week 24 and also planned at Week 48 by polymerase chain reaction (PCR) analysis. Data is reported for number of participants with plasma HIV-1 RNA \<400 copies/mL at Week 24. Data was not collected for Week 48 due to early termination of the study.
Number of Participants With >= 1.0 log10 Copies/mL Decrease in Plasma HIV-1 RNA From Baseline Over Time
时间窗: Day 1 up to Week 12 Follow-up of the Randomized Treatment phase, up to Week 12 Follow-up of the Open Labeled Non-Randomized phase and every 6 months Follow-up of off study drug/on study phase
The plasma HIV-1 RNA polymerase chain reaction (PCR) assessments were planned at pre-Baseline (between 1 and 14 days prior to Day 1), up to Week 12 Follow- up of the Randomized Phase, up to Week 12 Follow-up of the Open Labeled Non-Randomized phase and every 6 months Follow-up of off study drug/on study phase, however the study was early terminated at Week 40. Baseline was defined as the mean of the Baseline (Day 1) and pre-treatment visit values.
Average Area Under the Curve Minus Baseline (AAUCMB) of Plasma HIV-1 RNA Through the Entire Study Period
时间窗: Up to Week 40
The area under the plasma HIV-1 RNA curve (AUC) was computed using the trapezoidal rule for all assessments (scheduled and unscheduled) at their actual time points. Baseline was defined as the mean of the Baseline (Day 1) and pre-treatment visit values. Participants without a Baseline assessment was removed from the analysis. The AAUCMB was computed by the AUC divided by the duration of the profile (i.e., the number of days on randomized therapy) minus the Baseline measurement. Data is reported up to Week 40 only due to early termination of the study.
次要结局
- Change From Baseline in Chemistry Parameter of Lipase During the Randomized Treatment Phase(Baseline (Day 1), Week 12 and Week 24)
- Change From Baseline in Haematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, White Blood Cell (WBC) Count During the Randomized Treatment Phase(Baseline (Day 1), Week 12 and Week 24)
- Number of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 24 and 48(Week 24)
- Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), Death, Drug-related AE and AE Leading to Treatment Discontinuation(Up to Follow-up (Week 52))
- Number of Participants With Treatment Emergent Laboratory Abnormalities for Chemistry Data at Any Visit Post-Baseline(Up to Week 40)
- Change From Baseline in Chemistry Parameters of ALT, ALP, AST and CK During the Randomized Treatment Phase(Baseline (Day 1), Week 12 and Week 24)
- Change From Baseline in Chemistry Parameters of CO2 Content/Bicarbonate, Chloride, Cholesterol, Glucose, High DL Cholesterol, LDL Cholesterol, Triglycerides, Potassium, Urea and Sodium During the Randomized Treatment Phase(Baseline (Day 1), Week 12 and Week 24)
- Change From Baseline in Chemistry Parameter of Creatinine and Total Bilirubin During the Randomized Treatment Phase(Baseline (Day 1), Week 12 and Week 24)
- Change From Baseline in Chemistry Parameter of Albumin During the Randomized Treatment Phase(Baseline (Day 1), Week 12 and Week 24)
- Change From Baseline in Haematology Parameter of Mean Corpuscle Volume (MCV) During the Randomized Treatment Phase(Baseline (Day 1), Week 12 and Week 24)
- Change From Baseline in Haematology Parameter of Hematocrit During the Randomized Treatment Phase.(Baseline (Day 1), Week 12 and Week 24)
- Change From Baseline in Haematology Parameter of Hemoglobin During the Randomized Treatment Phase(Baseline (Day 1), Week 12 and Week 24)
- Change From Baseline in Electrocardiograph (ECG) Parameter of Heart Rate (HR) During the Randomized Treatment Phase(Baseline (Day 1), Week 4 and Week 24)
- Change From Baseline in ECG Parameter of RR Interval, Uncorrected QT Interval, QTc Interval (Fridericia), QTc Interval (Bazette), PR Interval and QRS Duration During the Randomized Treatment Phase(Baseline (Day 1), Week 4 and Week 24)
- Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Counts During the Randomized Treatment Phase(Baseline (Day 1), Week 12, Week 24 and Week 40)
- Time to Centres for Disease Control and Prevention (CDC) Class C Acquired Immune Deficiency Syndrome (AIDS)-Defining Event or Death(Up to Week 12 Follow-up of the Randomized phase, up to Week 12 Follow-up of the Open Labeled Non-Randomized phase and every 6 months Follow-up of off study drug/on study phase)
- Number of Participants With Development of Antiretroviral Resistance to GW873140 400 mg BID and Other Antiretroviral Drugs(Up to Follow-up (Week 52))
- Number of Participants With 50% Inhibitory Concentration (IC50) Fold Resistance at Baseline(Baseline (Day 1))
- Plasma GW873140 400 mg BID Pharmacokinetic (PK) Parameter of Area Under the Plasma Concentration-time Curve During One Dosing Interval of Length (Tau) (AUC [0-tau]) During the Randomized Treatment Phase(Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose))
- Plasma GW873140 400 mg BID PK Parameter of Maximum Observed Plasma Concentration (Cmax) During the Randomized Treatment Phase(Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose))
- Plasma GW873140 400 mg BID PK Parameter of Time of Maximum Observed Plasma Concentration (Tmax) During the Randomized Treatment Phase(Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose))
- Plasma GW873140 400 mg BID PK Parameter of Concentration at End of Dosing Interval (Trough Concentration [Cτ]) During the Randomized Treatment Phase(Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose))
- Number of Participants With the Impact on Health Related Quality of Life Measured by Euro Quality of Life (Qol) Questionnaire During the Randomized Treatment Phase(Up to Week 48)
- Investigational Product Adherence Measured by Pill Counts(Up to Week 48 of Randomized Treatment phase and up to Switch + 24 Weeks of the Open Labeled phase)
- Number of Participants Who Were Bothered by Each of Several Specific Symptoms Evaluated Using the HIV Symptom Index Questionnaire During the Randomized Treatment Phase(Upto Week 48)