A Phase I/II Study of Invirase® Boosted With Ritonavir in HIV Infected Infants and Children 4 Months to Less Than 6 Years Old
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 主要终点
- Change In Hematocrit From Baseline
研究概览
简要总结
This single arm study will assess the pharmacokinetics, safety and activity of saquinavir (Invirase hard gel capsules, film coated tablets or opened capsules) boosted by combination with ritonavir, in HIV-1 infected infants and children between the ages of 4 months and 6 years. Patients will commence treatment with saquinavir 50mg/kg bid plus ritonavir 2.5mg/kg or 3.0mg/kg (dependent on body weight), and a background antiretroviral regimen. If drug exposures are found to be dissimilar to those previously seen in older children and adults, or are associated with toxicities, subsequent dose adjustments will be made. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Months 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •infants and children, 4 months to <6 years;
- •confirmed HIV-1 infection;
- •patients for whom saquinavir/ritonavir together with >=2 background ARVs is considered appropriate.
排除标准
- •body weight >4kg/8.8 pounds;
- •use of any concomitant medications that may interfere with the pharmacokinetics of saquinavir or ritonavir;
- •malabsorption, severe chronic diarrhea or vomiting within 28 days of the study.
研究组 & 干预措施
1
干预措施: ritonavir (Drug)
1
干预措施: saquinavir [Invirase] (Drug)
结局指标
主要结局
Change In Hematocrit From Baseline
时间窗: Baseline (Day 1), Week 24 and Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change In Red Blood Cell (RBC) Counts From Baseline
时间窗: Baseline (Day 1), Week 24 and Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Plasma Trough Concentrations (Ctrough) for Saquinavir
时间窗: Pre-dose at Weeks 8, 12, 24.
Plasma trough concentration is the average steady state concentration prior to morning and evening dose. Ctrough of Saquinavir was normalized to a dose of 50 mg/kg.
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Saquinavir
时间窗: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an Non-nucleoside reverse transcriptase inhibitor [NNRTI] containing regimen).
The area under the plasma concentration-time curve from time zero to twelve hours (AUC0-12h) is area under the plasma concentration-time curve from time zero through actual tlast. The area under the plasma concentration-time curve from time zero to twelve hours of saquinavir was normalized to a dose of 50 mg/kg.
Incidence of Adverse Events (AE) and Serious Adverse Events (SAE)
时间窗: From Baseline (Day 1) till Week 48 and Follow-up (Week 52)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline
时间窗: Baseline (Day 1), Week 24 and Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change In Hemoglobin, Total Protein And Total Albumin From Baseline
时间窗: Baseline (Day 1), Week 24 and Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline
时间窗: Baseline (Day 1), Week 24 and Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change In Total Bilirubin, Creatinine, Uric Acid From Baseline
时间窗: Baseline (Day 1), Week 24 and Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline
时间窗: Baseline (Day 1), Week 24 and Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change In Hematuria, Glycosuria And Proteinuria From Baseline
时间窗: Baseline (Day 1), Week 24 and Week 48
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
次要结局
- Change From Baseline in Mean Human Immunodeficiency Virus Viral Load(Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks.)
- Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <400 Copies/mL(Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks.)
- Maximum Observed Concentration (Cmax) for Saquinavir and Ritonavir(Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an NNRTI containing regimen and at Week 24)
- Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Ritonavir(Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an NNRTI containing regimen).)
- Plasma Trough Concentrations (Ctrough) for Ritonavir(Pre-dose at Weeks 8, 12, 24)
- Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <50 Copies/mL(Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks.)
- Number of Participants With >1 Log Decrease From Baseline in Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA )(From Week 8 till Week 48)
- Number of Participants With Virological Failure(From Week 12 till Week 48)
- Change From Baseline in Cluster Differentiation Antigen 4 (CD4) Lymphocyte Count(Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation)
- Change From Baseline in Cluster Differentiation Antigen 8 (CD8) Lymphocyte Count(Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation)