A Prospective Single Arm, Open-label, International, Multicenter Study to Evaluate the Safety of Atazanavir (ATV) Capsule Boosted With Ritonavir (RTV) With an Optimized NRTI Background Therapy, in HIV Infected, Antiretroviral Naive and Experienced Pediatric Subjects Greater Than or Equal to 6 Years to Less Than 18 Years
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 108
- 试验地点
- 4
- 主要终点
- Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Grade 2-4 Related AEs, Grade 3-4 AEs, and Centers for Disease Control (CDC) Class C AIDS Events
研究概览
简要总结
The purpose of this study is to collect safety clinical data in HIV-infected pediatric patients aged 6 and older to younger than18 years and weighing 15 kg or more, who are receiving atazanavir capsule boosted with ritonavir and an optimized nucleoside reverse transcriptase inhibitor backbone therapy as part of their antiretroviral regimen.
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
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed HIV-1 infection diagnosed by protocol criteria
- •Male or female children, ≥ 6 years to <17 years 6 months of age at the time of first treatment
- •Antiretroviral-naïve or treatment-experienced participants with a detectable viral load
- •Antiretroviral-naïve participants must have genotypic sensitivity at screening to atazanavir and at least 2 nucleoside reverse transcriptase inhibitors (NRTIs), which have been approved for pediatric use and dosed per local country label
- •Antiretroviral-experienced participants must have documented genotypic and phenotypic sensitivity at screening to atazanavir (fold change in susceptibility <2.2) and at least 2 NRTIs, which have been approved for pediatric use and dosed per local country label.
排除标准
- •Experienced participants who received atazanavir with or without ritonavir at any time prior to study enrollment
- •Antiretroviral-naive or -experienced HIV-1 infected patients with contraindication to study medications
- •Documented cardiac conduction abnormality, significant cardiac dysfunction, or a history syncope
- •Family history of QTc interval syndrome, Brugada syndrome, right ventricular dysplasia, or a corrected QTc interval of >440 ms at screening
- •One of the following cardiac rhythm abnormalities documented on the screening electrocardiogram:
- •First degree atrioventricular (AV) block, as defined by protocol
- •Type I second degree AV block while awake, type II second degree AV block at any time, complete AV block at any time, or age-adjusted heart rate <2nd percentile
- •Coinfection with either hepatitis B or C virus
研究组 & 干预措施
Atazanavir, 150 mg + Ritonavir, 100 mg (weight:15 to <20 kg)
Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.
干预措施: Atazanavir (Drug)
Atazanavir, 150 mg + Ritonavir, 100 mg (weight:15 to <20 kg)
Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.
干预措施: Ritonavir (Drug)
Atazanavir, 200 mg + Ritonavir, 100 mg (weight: 20 to <40 kg)
Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.
干预措施: Atazanavir (Drug)
Atazanavir, 200 mg + Ritonavir, 100 mg (weight: 20 to <40 kg)
Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.
干预措施: Ritonavir (Drug)
Atazanavir, 300 mg + Ritonavir, 100 mg (weight: ≥ 40 kg)
Participants with baseline weight ≥ 40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.
干预措施: Atazanavir (Drug)
Atazanavir, 300 mg + Ritonavir, 100 mg (weight: ≥ 40 kg)
Participants with baseline weight ≥ 40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.
干预措施: Ritonavir (Drug)
结局指标
主要结局
Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Grade 2-4 Related AEs, Grade 3-4 AEs, and Centers for Disease Control (CDC) Class C AIDS Events
时间窗: From first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4 (Continued)
时间窗: After first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)
Blood urea nitrogen (\*upper limit of normal \[ULN\]): Grade (Gr) 1=1.25-2.5; Gr 2=2.6-5.0; Gr 3=5.1-10; Gr 4= \>10. Uric acid (mg/dL): Gr 1=7.5-10.0; Gr 2=10.1-12; Gr 3=12.1-15.0; Gr 4= \>15.0. Bicarbonate (mEqL): Gr 1= 19.0-21.0; Gr 2=15.0-18.0; Gr 3=41-45; Gr 4= \>45. Calcium, low (mg/dL): Gr 1=7.8-8.4; Gr 2=7.0-7.7; Gr 3=6.1-6.9; Gr 4= \<6.1.Potassium (mEq/L), high: Gr 1=5.6-6.0; Gr 2=6.1-6.5; Gr 3=6.6-7.0; Gr 4= \>7.0. Potassium (mEq/L), low: Gr 1=3.1-3.4; Gr 2=2.5-2.9; Gr 3=2.0-2.4; Gr 4= \<2.0. Sodium (mEq/L), low: Gr 1=130-135; Gr 2=125-129; Gr 3=121-124; Gr 4= \<1. Total cholesterol, fasting (mg/dL): Gr 1=200-239; Gr 2=240-300; Gr 3= \>300; Gr 4=Not applicable (NA). Low-density lipoprotein (LDL) cholesterol, fasting (mg/dL): Gr 1=130-159; Gr 2=160-190; Gr 3= \>190; Gr 4= NA. Glucose, low (mg/dL): Gr 1= 55-64; Gr 2=40-54; Gr 3=30-39; Gr 4= \<30. Glucose, fasting (mg/dL): Gr 1=110-125; Gr 2=126-250; Gr 3=251-500; Gr 4 \>500.
Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4
时间窗: After first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)
Hematocrit (%): Grade (Gr) 1= ≥28.5- \<31.5; Gr 2= ≥24- \<28.5; Gr 3= ≥19.5- \<24; Gr 4= \<19.5. Hemoglobin (g/dL): Grade (Gr)1=8.5-10.0; Gr 2=7.5-8.4; Gr 3=6.50-7.4; Gr 4= \<6.5. Platelets (/mm\^3): Gr 1=100,000-124,999; Gr 2=50,000-99,999; Gr 3=25,000-49,999; Gr 4= \<25,000. White blood cells (/mm\^3): Gr 1=2000-2500; Gr 2=1500-1999; Gr 3=1000-1499; Gr 4= \<1000. Neutrophils (/mm\^3): Gr 1=1000-1500; Gr 2= ≥750-1000; Gr 3= ≥500-750; Gr 4= \<500. Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST) (\*upper limit of normal \[ULN\]): Gr 1=1.5-2.5; Gr 2=2.6-5.0; Gr 3=5.1-10.0; Gr 4= \>10.0. Total bilirubin (adult and pediatric \>14 days) (\*ULN): Gr 1=1.1-1.5; Gr 2=1.6-2.5; Gr 3=2.6-5.0; Gr 4= \>5.0. Albumin (g/dL): Gr 1= 3.1- \<LLN; Gr 2=2.0-2.9; Gr 3= \<2.0; Gr 4=NA. Amylase (\*ULN): Gr 1=1.10-1.39; Gr 2=1.40-2.09; Gr 3=2.10-5.0; Gr 4= \>5. Lipase (\*ULN): Gr 1=1.1-1.5; Gr 2=1.6-3.0; Gr 3=3.1-5.0; Gr 4= \>5.0.
次要结局
未报告次要终点