A Prospective Single Arm, Open-label, International, Multicenter Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Atazanavir (ATV) Powder Boosted With Ritonavir (RTV) With an Optimized NRTI Background Therapy, in Human Immunodeficiency Virus (HIV) Infected, Antiretroviral, Naive and Experienced Pediatric Subjects From 3 Months to Less Than 11 Years.(Pediatric Atazanavir International Clinical Evaluation: the PRINCE II Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 160
- 试验地点
- 3
- 主要终点
- Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality on ATV Powder
研究概览
简要总结
The purpose of this study is to describe the safety, efficacy, and pharmacokinetics of a regimen of atazanavir powder boosted with ritonavir and an optimized dual nucleoside reverse transcriptase inhibitor in pediatric patients aged ≥3 months to <11 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Months 至 11 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
- •Screening HIV RNA level ≥1000 copies/mL
- •≥3 months to <11 years of age at time of first treatment
- •Antiretroviral-naive or -experienced
- •At screening, all participants must have genotypic sensitivity to atazanavir and at least 2 nucleoside reverse transcriptase inhibitors (NRTIs), which must be approved for pediatric use at the local country.
- •Antiretroviral-experienced patients must also have documented phenotypic sensitivity at screening to atazanavir (Fold Change in susceptibility <2.2) and to at least 2 NRTIs that are approved in their country
排除标准
- •Experienced participants who received atazanavir or atazanavir/ritonavir at any time prior to study enrollment or who have a history of 2 or more protease inhibitor failures
- •Antiretroviral-naïve or -experienced HIV-1-infected patients with contraindication to study medications
- •Cardiac rhythm abnormalities
- •Need for tenofovir
- •Weight <5 or ≥35kg
- •>Grade 2 abnormality in aspartate transaminase/alanine transaminase levels
- •Coinfection with either hepatitis B or C virus
- •Any active Centers for Disease Control and Prevention Category C clinical condition
研究组 & 干预措施
Stage 1: Atazanavir + Ritonavir
Participants received atazanavir powder orally (dosed by weight: 5 to <10 kg=150 mg, 5 to <10 kg=200 mg, 10 to <15 kg=200 mg, 15 to <25 kg=250 mg, 25 to <35 kg=300 mg) once daily for 24 to 48 weeks or a weight ≥35 kg. Participants also received ritonavir once daily for 24 to 48 weeks or weight ≥35 kg in the form of 80-mg/mL solution, orally (dosed by weight 5 to <25 kg=80 mg, 25 to <35 kg=100 mg); 100-mg capsule, orally (dosed by weight 25 to <35 kg=100 mg); or 100-mg tablet, orally (dosed by weight 25 to <35 kg=100 mg)
干预措施: Atazanavir Sulphate (Drug)
Stage 1: Atazanavir + Ritonavir
Participants received atazanavir powder orally (dosed by weight: 5 to <10 kg=150 mg, 5 to <10 kg=200 mg, 10 to <15 kg=200 mg, 15 to <25 kg=250 mg, 25 to <35 kg=300 mg) once daily for 24 to 48 weeks or a weight ≥35 kg. Participants also received ritonavir once daily for 24 to 48 weeks or weight ≥35 kg in the form of 80-mg/mL solution, orally (dosed by weight 5 to <25 kg=80 mg, 25 to <35 kg=100 mg); 100-mg capsule, orally (dosed by weight 25 to <35 kg=100 mg); or 100-mg tablet, orally (dosed by weight 25 to <35 kg=100 mg)
干预措施: Ritonavir (Drug)
结局指标
主要结局
Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality on ATV Powder
时间窗: Day one to week 300 (approximately 22-Jan-2018)
Criteria of the Division of AIDS for grading the severity of adult and pediatric adverse events as follows: Grade (Gr) 1=mild; Gr 2=moderate; Gr 3=severe; Gr 4=potentially life-threatening. Neutrophils (absolute) (adult and infants \>7 days): Gr 1=1.000-1300/mm\^3; Gr 2=750-999 mm\^3; Gr 3=500-749 mm\^3; Gr 4= \<500 mm\^3. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase: Gr 1=1.25-2.5\*upper limit of normal (ULN); Gr 2=2.6-5.0\*ULN; Gr 3=5.1-10.0\*ULN; Gr 4= \>10.0\*ULN. Bilirubin, total (adults and infants \>14 days): Gr 1=1.1-1.5\*ULN; Gr 2=1.6-2.5\*ULN; Gr 3=2.6-5.0\*ULN; Gr 4= \>5.0\*ULN. Lipase: Gr 1=1.1-1.5\*ULN; Gr 2=1.6-3.0\*ULN; Gr 3=3.1-5.0\*ULN; Gr 4= \>5.0\*ULN. Bicarbonate, serum low: Gr 1=16.0 mEq/L-\<lower limit of normal; Gr 2=11.0-15.9 mEq/L; Gr 3=8.0-10.9 mEq/L; Gr 4= \<8 mEq/L. By criteria of the World Health Organization: Amylase: Gr 1=1.0-1.39\*ULN; Gr 2=1.40-2.09\*ULN; Gr 3.=2.10-5.0\*ULN; Gr 4= \>5.0\*ULN.
Number of Participants Who Died and With Adverse Events (AEs) Leading to Discontinuation, Hyperbilirubinemia, Jaundice, First-degree Arterioventricular Block, Tachycardia, and Rash on ATV Powder
时间窗: Day one to week 300 (approximately 22-Jan-2018)
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
Number of Participants Who Experienced a SAE on ATV Powder
时间窗: Day one to week 300 (approximately 22-Jan-2018)
SAE= any of the the following: is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event (defined as a medical event(s) that may not be immediately life threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the subject or may require intervention \[eg, medical, surgical\] to prevent one of the other serious outcomes listed in the definition above.) Examples of such events include, but are not limited to, intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization
Number of Participants With A Center of Disease Control and Prevention (CDC) Class C AIDS Event on ATV Powder
时间窗: Day one to week 300 (approximately 22-Jan-2018)
The CDC disease staging system assesses the severity of HIV disease by CD4 cell counts and by the presence of specific HIV-related conditions. CD4 counts are classified as 1: ≥500 cells/µL, 2: 200-499 cells/µL, and 3: \<200 cells/µL. Children with HIV infection are also classified in each of several categories. Category N: Not symptomatic. Category A: Mildly symptomatic. Category B: Moderately symptomatic. Category C: Severely symptomatic.
次要结局
- CD4 Cell Count Changes From Baseline on ATV Powder(Baseline to Weeks 24 and 48)
- Mean Change From Baseline in HIV RNA on ATV Powder(Baseline to Weeks 24 and 48)
- Mean Change From Baseline in CD4 Percent on ATV Powder(Baseline to Weeks 24 and 48)
- Number of Participants With HIV RNA <50 Copies/mL and <400 Copies/mL in the Week 24 Atazanavir Powder Cohort and the Eligible Week 48 Atazanavir Powder Cohort(Day 1 of treatment to weeks 24 and 48)
- Minimum Plasma Concentration (Cmin)(Baseline to Week 2)
- Number of Participants With Emergent Genotypic Substitutions on ATV Powder Through Week 48(Baseline through Week 48)
- Maximum Observed Plasma Concentration (Cmax)(Baseline to Week 2)
- Area Under the Concentration-Time Curve [AUC(TAU)](Baseline to Week 2)