An Open-label Study of Liquid and Sprinkled Formulations of Efavirenz Administered in Combination With Didanosine and Emtricitabine in HIV-infected Infants and Children 3 Months to 6 Years of Age.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) and Plasma Concentration 24 Hours Post-dose (Cmin) of EFV at Week 2 - Pharmacokinetic Evaluable Population
研究概览
简要总结
The primary purpose of this study is to find the dose of Efavirenz for young children. The safety and how the medication is tolerated will also be studied.
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
- 3 Months 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 infected; >=3 months of age to <=6 years of age (at time of treatment); screening plasma viral load >=1000 copies/mL
排除标准
- •Genotypic or phenotypic resistance to EFV, ddl, or FTC/lamivudine (3TC) at screening
研究组 & 干预措施
EFV+ddI+FTC in patients >= 3 months to < 6 months
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
干预措施: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC) (Drug)
EFV+ddI+FTC in patients >=6 months to < 2 years
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
干预措施: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC) (Drug)
EFV+ddI+FTC in patients >= 2 years to < 3 years
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
干预措施: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC) (Drug)
EFV+ddI+FTC in patients >= 3 years to <= 6 years
EFV (efavirenz) was administered in accordance with weight-based dosing nomograms and included one of the following preparations in a once a day (QD) dose: EFV capsules (50 and 200 mg) contents mixed with formula or a small amount of food vehicle, or oral solution (30 mg/mL. In addition, the following 2 drugs were administered: ddI (didanosine) (Pediatric Powder for Oral Solution or capsules of enteric-coated beads): 240 mg/m^2 QD; maximum daily dose of 400 mg and FTC (emtricitabine) (solution or tablets) 6 mg/kg QD; maximum daily dose of 240 mg.
干预措施: Efavirenz (EFV) + Didanosine (ddI) + Emtricitabine (FTC) (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) and Plasma Concentration 24 Hours Post-dose (Cmin) of EFV at Week 2 - Pharmacokinetic Evaluable Population
时间窗: Week 2
Cmax and Cmin were derived from plasma concentrations versus time using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. Cmax and Cmin were recorded directly from experimental observations. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. Cmax and Cmin were measured in ng/mL.
Area Under the Plasma Concentration Time Curve (AUC) Over One Dosing Interval From Time Zero to 24 Hours Post-dose(TAU) at Week 2 - Pharmacokinetic Evaluable Population
时间窗: Week 2
Plasma concentrations were obtained using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. AUC(TAU) was calculated by log- and linear trapezoidal summations. If a concentration was \< LLOQ at time TAU, the value of the concentration at time TAU was estimated using the quotient of the last quantifiable concentration and λ. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters summarized using geometric means. AUC(TAU) was measured in micromolars\*time (µM•h).
Apparent Oral Clearance (CLT/F) of EFV at Week 2 - Pharmacokinetic Evaluable Population
时间窗: Week 2
Plasma concentrations of EFV were obtained using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. CLT/F was calculated by dividing the dose of EFV by AUC(TAU) of EFV. Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F was measured in liters per hour (L/h).
Apparent Oral Clearance Adjusted for Body Weight (CLT/F/kg) of EFV at Week 2 - Pharmacokinetic Evaluable Population
时间窗: Week 2
Plasma concentrations of EFV were determined using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The lower limit of quantification (LLOQ) for EFV was 10.0 nanograms per milliliter (ng/mL) and the upper limit of quantification (ULOQ) was 8,000 ng/mL. CLT/F/kg was calculated by dividing CLT/F by body weight in kilograms (kg). Blood samples were collected before study drug administration and at 0.5, 1, 3, 5, 8, and 24 hours after study drug administration from an indwelling catheter or by direct venipuncture and the pharmacokinetic parameters were summarized using geometric means. CLT/F/kg was measured in liters per hour per kilogram (L/h/kg).
次要结局
- Log10 c/mL HIV RNA Changes From Baseline Through Week 48 - Treated Participants(Baseline through Week 48)
- The Number of Participants With Plasma HIV RNA < 400 Copies Per Milliliter (c/mL) at Week 48 as Analyzed by Different Algorithms - All Treated Participants(Week 48)
- The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Week 48 as Analyzed by Different Algorithms - All Treated Participants(Week 48)
- The Number of Participants With Plasma HIV RNA Levels < 400 c/mL at Week 24 as Analyzed by Different Algorithms - All Treated Participants(Week 24)
- The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Week 24 as Analyzed by Different Algorithms - All Treated Participants(Week 24)
- CD4 Cell Count Change From Baseline at Weeks 24 and 48 - Treated Participants(Baseline to Weeks 24 and 48)
- Percent of CD4 Cells Change From Baseline at Weeks 24 and 48 - Treated Participants(Baseline to Weeks 24 and 48)
- Number of Participants With On-Treatment Adverse Events (AEs), Related Adverse Events, Serious Adverse Events (SAEs), Death, Discontinuation Due to Adverse Events, and CDC Class C AIDS Events(Baseline to Week 96)
- Number of Participants With Liver Function Test Laboratory Abnormalities - Treated Population(Baseline to Week 96)
- Number of Participants With Lipid and Glucose Laboratory Abnormalities - Treated Participants(Baseline to Week 96)
- Number of Participants With Serum Chemistry Abnormalities - Treated Participants(Baseline to Week 96)
- Number of Participants With Hematologic Abnormalities - Treated Participants(Baseline to Week 96)
- Number of Treated Participants With Resistance Associated Genotypic and Phenotypic Changes in Viruses - Participants With Virologic Failure, Lack of Suppression or Viral Load Rebound(Baseline to Week 48)
- Number of Participants With Acquisition of Resistance to EFV Categorized by AUC Relationship - Evaluable Pharmacokinetic Population(Baseline to Week 48)
- Cmax and Cmin of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population(Week 2)
- AUC (TAU) of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population(Week 2)
- CLT/F of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population(Week 2)
- CLT/F/kg of Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population(Week 2)
- Terminal Phase Elimination Half-life (T-HALF) in Didanosine (ddI) at Week 2 - Pharmacokinetic Evaluable Population(Week 2)
- The Number of Participants With Plasma HIV RNA Levels < 400 c/mL at Weeks 60, 72, 84 and 96 (Observed Cases) - All Treated Participants(Weeks 60, 72, 84, and 96)
- The Number of Participants With Plasma HIV RNA Levels < 50 c/mL at Weeks 60, 72, 84 and 96 (Observed Cases) - All Treated Participants(Weeks 60, 72, 84, and 96)
- Log10 c/mL HIV RNA Changes From Baseline at Weeks 60, 72, 84 and 96 - Treated Participants(Baseline through Weeks 60, 72, 84, and 96)
- CD4 Cell Count Change From Baseline at Weeks 60, 72, 84, and 96 - Treated Participants(Baseline to Weeks 60, 72, 84, and 96)
- Percent of CD4 Cells Change From Baseline at Weeks 60, 72, 84, and 96 - Treated Participants(Baseline to Weeks 60, 72, 84, and 96)