A Phase 1b Study to Evaluate the Safety and Pharmacokinetics of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in Neonates Exposed to HIV-1
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 16
- 试验地点
- 7
- 主要终点
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAs) Though Week 8 After Neonate Birth
研究概览
简要总结
The goal of this clinical study is to learn more about the study drug, Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), safety, tolerability, and pharmacokinetics (how B/F/TAF is absorbed, modified, distributed, and removed from the body of the participants) in neonates exposed to human immunodeficiency virus type 1 (HIV-1).
The primary objective of this study is to evaluate the safety and plasma pharmacokinetics (PK) (how B/F/TAF is absorbed, modified, distributed, and removed from the body of the participants) of B/F/TAF tablet for oral suspension (TOS) in full-term neonates exposed to HIV-1 but uninfected.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 120 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mother inclusion criteria:
- •Be on standard of care (SOC) antiretroviral therapy for human immunodeficiency virus type 1 (HIV-1) treatment.
- •Have confirmed HIV-1 infection based on positive test results obtained from medical records.
- •Neonate inclusion criteria:
- •Be born at term (≥ 37.0 weeks gestational age).
- •Be able to take oral medication.
- •Be ≤ 120 hours of life at enrollment.
- •Have a birth weight ≥ 2.5 kg.
- •Is receiving or plans to receive HIV-1 SOC prophylaxis regimen with 1 antiretroviral (ARV) to prevent perinatal transmission.
排除标准
- •Mother exclusion criteria:
- •Has a maternal-fetal blood group incompatibility identified by clinically relevant antibody that can cause hemolytic diseases of the neonate.
- •Is breastfeeding or plans to breastfeed while on bictegravir (BIC) or emtricitabine (FTC) containing regimen. Mothers on BIC or FTC containing regimen, but not breastfeeding, can be enrolled in the study.
- •Neonate exclusion criteria:
- •Had prior or expected to require blood exchange transfusion.
- •Is receiving or plans to receive any component of B/F/TAF or dolutegravir as part of their SOC ARV prophylaxis regimen.
- •Has a documented positive HIV-1 nucleic acid test.
- •Has Grade 2 or higher aspartate aminotransferase, total bilirubin, hemoglobin, platelets or creatinine. Has Grade 1 or higher alanine aminotransferase.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1: Group A of B/F/TAF
Full-term neonate participants, who are exposed to HIV-1 but uninfected, with a weight of ≥ 2.5 kg at birth and their mothers will be assigned to Cohort 1 Group A to evaluate a different pharmacokinetic (PK) sampling scheme than Cohort 1 Group B.
Neonate participants will receive a single dose of B/F/TAF fixed-dose combination 1.88/7.5/0.94 mg tablet for oral suspension administered along with 1 antiretroviral as standard of care postnatal prophylaxis at both Visits 1 and 3.
干预措施: B/F/TAF (Drug)
Cohort 1: Group B of B/F/TAF
Once enrollment in Cohort 1 Group A is completed, full-term neonate participants, who are exposed to HIV-1 but uninfected, with a weight of ≥ 2.5 kg at birth and their mothers will be assigned to Cohort 1 Group B to evaluate a different PK sampling scheme than Cohort 1 Group A.
Participants will receive a single dose of B/F/TAF fixed-dose combination 1.88/7.5/0.94 mg tablet for oral suspension administered along with 1 antiretroviral as standard of care postnatal prophylaxis at both Visits 1 and 3.
干预措施: B/F/TAF (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAs) Though Week 8 After Neonate Birth
时间窗: First dose date up to 8 Weeks
Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 8 After Neonate Birth
时间窗: First dose date up to 8 Weeks
Pharmacokinetic (PK) parameters for Bictegravir (BIC): AUCinf
时间窗: Predose up to 72 hours postdose
AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time.
PK parameters for BIC: AUClast
时间窗: Predose up to 72 hours postdose
AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.
PK parameters for BIC: AUC0-24h
时间窗: Predose up to 24 hours postdose
AUC0-24h is defined as the partial area under the concentration versus time curve from time 0 to time 24 hours.
PK parameters for BIC: Cmax
时间窗: Predose up to 72 hours postdose
Cmax is defined as the maximum observed concentration of drug.
PK parameters for BIC: Tmax
时间窗: Predose up to 72 hours postdose
Tmax is defined as the time (observed time point) of Cmax.
PK parameters for BIC: Cmin
时间窗: Predose up to 72 hours postdose
Cmin is defined as the minimum observed concentration of drug.
PK parameters for BIC: C24h
时间窗: At 24 hours postdose
C24h is defined as the concentration of drug at time 24 hours.
PK parameters for BIC: t1/2
时间窗: Predose up to 72 hours postdose
t1/2 is defined as the terminal elimination half-life.
PK parameters for BIC: Apparent CL/F
时间窗: Predose up to 72 hours postdose
Apparent CL/F is defined as the apparent total body clearance for extravascular administration.
PK parameters for BIC: Apparent Vz/F
时间窗: Predose up to 72 hours postdose
Apparent Vz/F is defined as the apparent volume of distribution based on the terminal phase.
PK parameters for BIC: AUC0-24h
时间窗: Predose up to 24 hours postdose
AUC0-24h is defined as the partial area under the concentration versus time curve from time 0 to time 24 hours.
PK parameters for BIC: Cmax
时间窗: Predose up to 72 hours postdose
Cmax is defined as the maximum observed concentration of drug.
PK parameters for BIC: Tmax
时间窗: Predose up to 72 hours postdose
Tmax is defined as the time (observed time point) of Cmax.
PK parameters for BIC: Cmin
时间窗: Predose up to 72 hours postdose
Cmin is defined as the minimum observed concentration of drug.
PK parameters for BIC: t1/2
时间窗: Predose up to 72 hours postdose
t1/2 is defined as the terminal elimination half-life.
PK parameters for BIC: Apparent CL/F
时间窗: Predose up to 72 hours postdose
Apparent CL/F is defined as the apparent total body clearance for extravascular administration.
PK parameters for BIC: Apparent Vz/F
时间窗: Predose up to 72 hours postdose
Apparent Vz/F is defined as the apparent volume of distribution based on the terminal phase.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAs) Though Week 8 After Neonate Birth
时间窗: First dose date up to 8 Weeks
Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 8 After Neonate Birth
时间窗: First dose date up to 8 Weeks
PK parameters for BIC: AUClast
时间窗: Predose up to 72 hours postdose
AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.
次要结局
- PK parameters for FTC, TAF, and TFV: AUClast(Predose up to 72 hours postdose)
- PK parameters for FTC, TAF, and TFV: AUC0-24h(Predose up to 24 hours postdose)
- PK parameters for FTC, TAF, and TFV: Cmax(Predose up to 72 hours postdose)
- PK parameters for FTC, TAF, and TFV: Tmax(Predose up to 72 hours postdose)
- PK parameters for FTC, TAF, and TFV: Cmin(Predose up to 72 hours postdose)
- PK parameters for FTC, TAF, and TFV: C24h(At 24 hours postdose)
- PK parameters for FTC, TAF, and TFV: t1/2(Predose up to 72 hours postdose)
- PK parameters for FTC and TAF: Apparent CL/F(Predose up to 72 hours postdose)
- PK parameters for FTC and TAF: Apparent Vz/F(Predose up to 72 hours postdose)
- Mother/Caregiver Reported Acceptability of B/F/TAF tablet for oral suspension (TOS)(First dose date up to 15 days)
- Mother/Caregiver Reported Palatability of B/F/TAF tablet for oral suspension (TOS)(First dose date up to 15 days)
- PK Parameters for Emtricitabine (FTC), and Tenofovir (TFV): AUCinf(Predose up to 72 hours postdose)
- PK parameters for FTC, TAF, and TFV: AUClast(Predose up to 72 hours postdose)
- PK parameters for FTC, TAF, and TFV: AUC0-24h(Predose up to 24 hours postdose)
- PK parameters for FTC, TAF, and TFV: Cmax(Predose up to 72 hours postdose)
- PK parameters for FTC, TAF, and TFV: Tmax(Predose up to 72 hours postdose)
- PK parameters for FTC, TAF, and TFV: Cmin(Predose up to 72 hours postdose)
- PK parameters for FTC, TAF, and TFV: C24h(At 24 hours postdose)
- PK parameters for FTC, TAF, and TFV: t1/2(Predose up to 72 hours postdose)
- PK parameters for FTC and TAF: Apparent CL/F(Predose up to 72 hours postdose)
- PK parameters for FTC and TAF: Apparent Vz/F(Predose up to 72 hours postdose)
- Mother/Caregiver Reported Acceptability of B/F/TAF tablet for oral suspension (TOS)(First dose date up to 15 days)
- Mother/Caregiver Reported Palatability of B/F/TAF tablet for oral suspension (TOS)(First dose date up to 15 days)