Study to Evaluate the Pharmacokinetics (PK), Safety, and Efficacy of B/F/TAF in Human Immunodeficiency Virus (HIV)-1 Infected, Virologically Suppressed, Pregnant Women in Their Second and Third Trimesters
- Conditions
- HIV-1-infection
- Interventions
- Drug: B/F/TAF
- Registration Number
- NCT03960645
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the steady state PK of bictegravir (BIC) and confirm the dose of BIC/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in HIV-1 infected, virologically suppressed pregnant women in their second and third trimesters.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 62
- The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- With singleton pregnancy, at least 12 weeks but not more than 31 weeks pregnant at the time of screening
- Agree not to breastfeed for the duration of the study
- Currently on a stable antiretroviral regimen for ≥ 6 months preceding the screening visit
- Documented plasma HIV-1 ribonucleic acid (RNA) levels of < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at the screening visit
- Have no documented or suspected resistance to FTC, Tenofovir (TFV), or integrase strand-transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R or M184V/I
- Have a normal ultrasound, completed locally prior to the Day 1 visit, with no evidence of any fetal malformation or structural abnormality affecting either fetus or placenta
- Normal maternal alfa-fetoprotein level at the screening visit
Key
- Have chronic hepatitis B virus (HBV)
- Have active hepatitis C virus (HCV) infection
- An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description B/F/TAF B/F/TAF Pregnant women participants will receive fixed dose combination (FDC) tablet of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg for up to 38 weeks (from the second or third trimesters of pregnancy, depending on enrollment, through 12 weeks post-partum).
- Primary Outcome Measures
Name Time Method Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC) Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
- Secondary Outcome Measures
Name Time Method PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: AUClast of BIC, FTC, and TAF Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: Cmax of BIC, FTC, and TAF Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum Cmax is defined as the maximum observed concentration of drug during the dosing interval.
PK Parameter: Ctau of BIC and FTC Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Clast of BIC, FTC, and TAF Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum Clast is defined as the last observable concentration of drug.
PK Parameter: Tmax of BIC, FTC, and TAF Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: t1/2 of BIC, FTC, and TAF Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: CLss/F of BIC, FTC, and TAF Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum CLss/F is defined as the apparent steady-state oral clearance following administration of the drug.
PK Parameter: Vz/F of BIC, FTC, and TAF Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum Vz/F is defined as the apparent volume of distribution of the drug.
PK Parameter: λz of BIC, FTC, and TAF Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at the Time of Delivery Using the Missing = Excluded Approach in B/F/TAF Group At time of delivery The percentage of participants with HIV-1 RNA \< 50 copies/mL at the time of delivery was analyzed in B/F/TAF group using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation).
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Birth Using the Missing = Excluded Approach in Neonates At birth The percentage of participants with HIV-1 RNA \< 50 copies/mL at the time of birth was analyzed in neonates using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation).
Trial Locations
- Locations (8)
Instituto Dominicano de Estudios Virologics (IDEV)
🇩🇴Santo Domingo, Dominican Republic
Thai Red Cross AIDS Research Centre
🇹🇭Pathumwan, Thailand
Faculty of Medicine-Khon Kaen University
🇹🇭Khon Kaen, Thailand
Faculty of Medicine Siriraj Hospital
🇹🇭Bangkok Noi, Thailand
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
Bamrasnaradura Infectious Diseases Institute
🇹🇭Mueang Nonthaburi, Thailand
Research Institute for Health Sciences, Chiang Mai University
🇹🇭Mueang Nonthaburi, Thailand