Pharmacokinetic, Safety, and Efficacy of B/F/TAF in HIV-1 Infected, Virologically Suppressed, Pregnant Women in Their Second and Third Trimesters
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate the steady state pharmacokinetics 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: B/F/TAF B/F/TAF for up to approximately 38 weeks |
Drug: B/F/TAF
50/200/25 mg FDC tablet administered orally once daily without regard to food
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic (PK) Parameter: AUCtau of BIC [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Secondary Outcome Measures
- PK Parameter: AUCtau of emtricitabine (FTC) and tenofovir alafenamide (TAF) [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
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 [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
- PK Parameter: Cmax of BIC, FTC, and TAF [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
Cmax is defined as the maximum observed concentration of drug during the dosing interval.
- PK Parameter: Ctau of BIC and FTC [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
Ctau is defined as the observed drug concentration at the end of the dosing interval.
- PK Parameter: Clast of BIC, FTC, and TAF [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
Clast is defined as the last observable concentration of drug.
- PK Parameter: Tmax of BIC, FTC, and TAF [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
Tmax is defined as the time (observed time point) of Cmax.
- PK Parameter: t1/2 of BIC, FTC, and TAF [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
- PK Parameter: CL/F of BIC, FTC, and TAF [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
CL/F is defined as the apparent oral clearance following administration of the drug.
- PK Parameter: Vz/F of BIC, FTC, and TAF [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
Vz/F is defined as the apparent volume of distribution of the drug.
- PK Parameter: λz of BIC, FTC, and TAF [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose]
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.
- Proportion of Participants With HIV-1 RNA < 50 Copies/mL Using the Missing = Excluded Approach [At the Time of Delivery]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
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 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
-
Historic genotype reports will be collected if available
-
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 Exclusion Criteria:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Miller Children's & Women's Hospital Long Beach | Long Beach | California | United States | 90806 |
| 2 | Midway Immunology and Research Center | Fort Pierce | Florida | United States | 34982 |
| 3 | University of South Florida | Tampa | Florida | United States | 33762 |
| 4 | Triple O Research Institute, P.A. | West Palm Beach | Florida | United States | 33407 |
| 5 | Duke University Health System | Durham | North Carolina | United States | 27710 |
| 6 | Instituto Dominicano de Estudios Virologics (IDEV) | Santo Domingo | Dominican Republic | 10103 | |
| 7 | Maternal Infant Studies Center (CEMI) | San Juan | Puerto Rico | 00925 | |
| 8 | Faculty of Medicine Siriraj Hospital | Bangkok Noi | Thailand | 10700 | |
| 9 | Faculty of Medicine-Khon Kaen University | Khon Kaen | Thailand | 40002 | |
| 10 | Bamrasnaradura Infectious Diseases Institute | Muang | Thailand | 11000 | |
| 11 | Research Institute for Health Sciences, Chiang Mai University | Muang | Thailand | 50200 | |
| 12 | Thai Red Cross AIDS Research Centre | Pathumwan | Thailand | 10330 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- GS-US-380-5310