HIV-1-infection
Conditions
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.
Interventions
DRUGB/F/TAF
50/200/25 mg FDC tablet administered orally once daily without regard to food.
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Study model 'single group' is selected as the Neonates group was only followed up but not treated.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
No
Inclusion 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 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
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: 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: 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: 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). |
| 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. |
Countries
Dominican Republic, Thailand, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the Dominican Republic, Thailand and the United States.
Pre-assignment details
33 pregnant women were enrolled in the B/F/TAF group. Neonates born to these women were also enrolled in the study for follow up. A total of 29 neonate participants were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| B/F/TAF Pregnant women participants received FDC tablet of B/F/TAF 50/200/25 mg, orally, once daily for up to 38 weeks (from the second or third trimesters of pregnancy, depending on enrollment, through 12 weeks post-partum). | 33 |
| Neonates Neonates born to women participants in the study were followed from birth up to 8 weeks of age after obtaining consent from the parent or legal guardian. None of the neonates participating in the study were treated with the study drug. | 29 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Neonates | Total | B/F/TAF |
|---|---|---|---|
| Age, Continuous | 0 years STANDARD_DEVIATION 0 | 16 years STANDARD_DEVIATION 15.5 | 30 years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 54 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 24 Participants | 49 Participants | 25 Participants |
| Race/Ethnicity, Customized Race Black | 4 Participants | 10 Participants | 6 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Dominican Republic | 3 Participants | 6 Participants | 3 Participants |
| Region of Enrollment Thailand | 24 Participants | 49 Participants | 25 Participants |
| Region of Enrollment United States | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Female | 10 Participants | 43 Participants | 33 Participants |
| Sex: Female, Male Male | 19 Participants | 19 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 29 |
| other Total, other adverse events | 19 / 33 | 4 / 29 |
| serious Total, serious adverse events | 6 / 33 | 5 / 29 |
Outcome results
Primary
Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC)
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: 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
Population: PK analysis set included all enrolled adult participants who took at least 1 dose of study drug (B/F/TAF), and had at least 1 non-missing concentration value reported by the PK laboratory for the corresponding analytes (BIC, FTC, TAF, and tenofovir diphosphate \[TFV-DP\]). Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B/F/TAF | Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC) | Third Trimester | 60163.4 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 17482.06 |
| B/F/TAF | Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC) | Week 6 Post-partum | 134820.3 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 36217.3 |
| B/F/TAF | Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC) | Second Trimester | 62772.2 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 20242.18 |
| B/F/TAF | Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC) | Week 12 Post-partum | 148251.6 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 42189.17 |
Comparison: BIC: Second Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% confidence interval (CI) was constructed for the geometric least squares mean (GLSM) ratio (%).90% CI: [36.71, 46.32]
Comparison: BIC: Second Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [40.04, 49.79]
Comparison: BIC: Third Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [36.77, 44.76]
Comparison: BIC: Third Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [39.95, 49.34]
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Birth Using the Missing = Excluded Approach in Neonates
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).
Time frame: At birth
Population: Neonate full analysis set included neonates who were born to women participating in the study and had been enrolled into the study as well. Participants in the neonate full analysis set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Birth Using the Missing = Excluded Approach in Neonates | 100.0 percentage of participants |
Secondary
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
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).
Time frame: At time of delivery
Population: Full analysis set included all adult participants who enrolled into the study and took at least 1 dose of study drug (B/F/TAF). Participants in the full analysis set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B/F/TAF | 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 | 100.0 percentage of participants |
Secondary
PK Parameter: AUClast of BIC, FTC, and TAF
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | TAF: Second Trimester | 220.4 h*ng/mL | Standard Deviation 98.98 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | TAF: Third Trimester | 202.2 h*ng/mL | Standard Deviation 84.98 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | TAF: Week 6 Post-partum | 356.7 h*ng/mL | Standard Deviation 151.27 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | BIC: Second Trimester | 63187.5 h*ng/mL | Standard Deviation 19814.99 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | BIC: Third Trimester | 60145.3 h*ng/mL | Standard Deviation 17484.52 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | BIC: Week 6 Post-partum | 135058.9 h*ng/mL | Standard Deviation 36348.21 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | BIC: Week 12 Post-partum | 148265.3 h*ng/mL | Standard Deviation 42201.47 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | FTC: Second Trimester | 10258.5 h*ng/mL | Standard Deviation 2049.53 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | FTC: Third Trimester | 10434.2 h*ng/mL | Standard Deviation 2121.13 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | FTC: Week 6 Post-partum | 16329.7 h*ng/mL | Standard Deviation 4095.44 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | FTC: Week 12 Post-partum | 15308.5 h*ng/mL | Standard Deviation 3359.79 |
| B/F/TAF | PK Parameter: AUClast of BIC, FTC, and TAF | TAF: Week 12 Post-partum | 294.3 h*ng/mL | Standard Deviation 97.88 |
Secondary
PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B/F/TAF | PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | FTC: Second Trimester | 10263.8 h*ng/mL | Standard Deviation 2054.35 |
| B/F/TAF | PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | FTC: Third Trimester | 10435.2 h*ng/mL | Standard Deviation 2121.87 |
| B/F/TAF | PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | FTC: Week 6 Post-partum | 16277.5 h*ng/mL | Standard Deviation 4023.42 |
| B/F/TAF | PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | FTC: Week 12 Post-partum | 15308.5 h*ng/mL | Standard Deviation 3359.83 |
| B/F/TAF | PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | TAF: Second Trimester | 235.5 h*ng/mL | Standard Deviation 107.36 |
| B/F/TAF | PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | TAF: Third Trimester | 212.1 h*ng/mL | Standard Deviation 95.38 |
| B/F/TAF | PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | TAF: Week 6 Post-partum | 374.3 h*ng/mL | Standard Deviation 153.54 |
| B/F/TAF | PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | TAF: Week 12 Post-partum | 296.4 h*ng/mL | Standard Deviation 94.37 |
Comparison: FTC: Second Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [63.45, 71.56]
Comparison: FTC: Second Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [60.95, 67.75]
Comparison: FTC: Third Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [65.88, 72.66]
Comparison: FTC: Third Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [61.79, 68.57]
Comparison: TAF: Second Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [65.4, 92.14]
Comparison: TAF: Second Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [50.76, 76.96]
Comparison: TAF: Third Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [58.57, 82.88]
Comparison: TAF: Third Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [46.32, 68.96]
Secondary
PK Parameter: Clast of BIC, FTC, and TAF
Clast is defined as the last observable concentration of drug.
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | BIC: Second Trimester | 1141.10 ng/mL | Standard Deviation 631.431 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | BIC: Third Trimester | 1075.13 ng/mL | Standard Deviation 447.847 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | BIC: Week 6 Post-partum | 3535.48 ng/mL | Standard Deviation 1371.162 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | BIC: Week 12 Post-partum | 3641.88 ng/mL | Standard Deviation 1240.605 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | FTC: Second Trimester | 75.08 ng/mL | Standard Deviation 130.792 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | FTC: Third Trimester | 51.65 ng/mL | Standard Deviation 14.182 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | FTC: Week 6 Post-partum | 156.16 ng/mL | Standard Deviation 292.579 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | FTC: Week 12 Post-partum | 81.18 ng/mL | Standard Deviation 27.334 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | TAF: Second Trimester | 4.49 ng/mL | Standard Deviation 5.13 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | TAF: Third Trimester | 4.80 ng/mL | Standard Deviation 4.048 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | TAF: Week 6 Post-partum | 3.13 ng/mL | Standard Deviation 1.849 |
| B/F/TAF | PK Parameter: Clast of BIC, FTC, and TAF | TAF: Week 12 Post-partum | 3.36 ng/mL | Standard Deviation 1.999 |
Secondary
PK Parameter: CLss/F of BIC, FTC, and TAF
CLss/F is defined as the apparent steady-state oral clearance following administration of the drug.
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | TAF: Week 6 Post-partum | 76939.32 mL/h | Standard Deviation 29189.555 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | TAF: Week 12 Post-partum | 92888.59 mL/h | Standard Deviation 29461.55 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | BIC: Second Trimester | 911.78 mL/h | Standard Deviation 433.301 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | BIC: Third Trimester | 902.47 mL/h | Standard Deviation 287.285 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | BIC: Week 6 Post-partum | 399.02 mL/h | Standard Deviation 113.214 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | BIC: Week 12 Post-partum | 362.40 mL/h | Standard Deviation 95.856 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | FTC: Second Trimester | 20228.02 mL/h | Standard Deviation 3981.186 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | FTC: Third Trimester | 19975.85 mL/h | Standard Deviation 4223.365 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | FTC: Week 6 Post-partum | 12991.62 mL/h | Standard Deviation 3111.349 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | FTC: Week 12 Post-partum | 13645.71 mL/h | Standard Deviation 2830.897 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | TAF: Second Trimester | 122677.74 mL/h | Standard Deviation 44270.041 |
| B/F/TAF | PK Parameter: CLss/F of BIC, FTC, and TAF | TAF: Third Trimester | 135061.19 mL/h | Standard Deviation 44876.97 |
Secondary
PK Parameter: Cmax of BIC, FTC, and TAF
Cmax is defined as the maximum observed concentration of drug during the dosing interval.
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | BIC: Second Trimester | 5819.0 ng/mL | Standard Deviation 1752.29 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | BIC: Third Trimester | 5374.7 ng/mL | Standard Deviation 1393.86 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | BIC: Week 6 Post-partum | 9765.5 ng/mL | Standard Deviation 2274.93 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | BIC: Week 12 Post-partum | 11025.3 ng/mL | Standard Deviation 2747.42 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | FTC: Second Trimester | 2639.1 ng/mL | Standard Deviation 965.6 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | FTC: Third Trimester | 2586.0 ng/mL | Standard Deviation 686.42 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | FTC: Week 6 Post-partum | 3394.8 ng/mL | Standard Deviation 951.83 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | FTC: Week 12 Post-partum | 3360.0 ng/mL | Standard Deviation 902.47 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | TAF: Second Trimester | 332.4 ng/mL | Standard Deviation 173.29 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | TAF: Third Trimester | 270.9 ng/mL | Standard Deviation 113.93 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | TAF: Week 6 Post-partum | 506.4 ng/mL | Standard Deviation 249.33 |
| B/F/TAF | PK Parameter: Cmax of BIC, FTC, and TAF | TAF: Week 12 Post-partum | 494.6 ng/mL | Standard Deviation 259.51 |
Comparison: BIC: Second Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [46.48, 57.97]
Comparison: BIC: Second Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [52.48, 63.36]
Comparison: BIC: Third Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [43.03, 53.94]
Comparison: BIC: Third Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [48.39, 61.21]
Comparison: FTC: Second Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [66.7, 85.7]
Comparison: FTC: Second Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [68.76, 88.05]
Comparison: FTC: Third Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [70.33, 85.29]
Comparison: FTC: Third Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [69.78, 85.15]
Comparison: TAF: Second Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [56.16, 87]
Comparison: TAF: Second Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [53.79, 82.34]
Comparison: TAF: Third Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [46.04, 70.91]
Comparison: TAF: Third Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [44.65, 68.42]
Secondary
PK Parameter: Ctau of BIC and FTC
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B/F/TAF | PK Parameter: Ctau of BIC and FTC | BIC: Second Trimester | 1046.4 ng/mL | Standard Deviation 472.68 |
| B/F/TAF | PK Parameter: Ctau of BIC and FTC | BIC: Third Trimester | 1072.4 ng/mL | Standard Deviation 447.03 |
| B/F/TAF | PK Parameter: Ctau of BIC and FTC | BIC: Week 6 Post-partum | 3530.3 ng/mL | Standard Deviation 1354.2 |
| B/F/TAF | PK Parameter: Ctau of BIC and FTC | BIC: Week 12 Post-partum | 3641.9 ng/mL | Standard Deviation 1241.64 |
| B/F/TAF | PK Parameter: Ctau of BIC and FTC | FTC: Second Trimester | 59.8 ng/mL | Standard Deviation 62.17 |
| B/F/TAF | PK Parameter: Ctau of BIC and FTC | FTC: Third Trimester | 51.4 ng/mL | Standard Deviation 13.98 |
| B/F/TAF | PK Parameter: Ctau of BIC and FTC | FTC: Week 6 Post-partum | 152.1 ng/mL | Standard Deviation 271.5 |
| B/F/TAF | PK Parameter: Ctau of BIC and FTC | FTC: Week 12 Post-partum | 81.1 ng/mL | Standard Deviation 27.34 |
Comparison: BIC: Second Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [21.45, 31.93]
Comparison: BIC: Second Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [22.23, 32.78]
Comparison: BIC: Third Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [25.74, 32.74]
Comparison: BIC: Third Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [26.47, 33.93]
Comparison: FTC: Second Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [54.63, 75.49]
Comparison: FTC: Second Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [36.55, 50.34]
Comparison: FTC: Third Trimester (Test) vs. Week 12 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [59.3, 70.61]
Comparison: FTC: Third Trimester (Test) vs. Week 6 Post-partum (Reference). A 90% CI was constructed for the GLSM ratio (%).90% CI: [39.57, 55.64]
Secondary
PK Parameter: t1/2 of BIC, FTC, and TAF
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | BIC: Second Trimester | 9.09 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | BIC: Third Trimester | 9.91 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | BIC: Week 6 Post-partum | 18.24 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | BIC: Week 12 Post-partum | 17.27 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | FTC: Second Trimester | 6.43 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | FTC: Third Trimester | 6.41 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | FTC: Week 6 Post-partum | 6.27 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | FTC: Week 12 Post-partum | 5.76 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | TAF: Second Trimester | 0.30 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | TAF: Third Trimester | 0.28 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | TAF: Week 6 Post-partum | 0.40 h |
| B/F/TAF | PK Parameter: t1/2 of BIC, FTC, and TAF | TAF: Week 12 Post-partum | 0.35 h |
Secondary
PK Parameter: Tmax of BIC, FTC, and TAF
Tmax is defined as the time (observed time point) of Cmax.
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | BIC: Second Trimester | 2.00 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | BIC: Third Trimester | 2.00 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | BIC: Week 6 Post-partum | 1.50 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | BIC: Week 12 Post-partum | 1.50 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | FTC: Second Trimester | 1.50 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | FTC: Third Trimester | 1.50 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | FTC: Week 6 Post-partum | 1.50 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | FTC: Week 12 Post-partum | 1.00 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | TAF: Second Trimester | 0.75 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | TAF: Third Trimester | 1.00 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | TAF: Week 6 Post-partum | 0.75 h |
| B/F/TAF | PK Parameter: Tmax of BIC, FTC, and TAF | TAF: Week 12 Post-partum | 0.75 h |
Secondary
PK Parameter: Vz/F of BIC, FTC, and TAF
Vz/F is defined as the apparent volume of distribution of the drug.
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | BIC: Second Trimester | 11896.24 mL | Standard Deviation 4417.149 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | BIC: Third Trimester | 13406.77 mL | Standard Deviation 4349.429 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | BIC: Week 6 Post-partum | 10348.47 mL | Standard Deviation 3713.38 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | BIC: Week 12 Post-partum | 8692.59 mL | Standard Deviation 2398.645 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | FTC: Second Trimester | 181767.32 mL | Standard Deviation 36739.344 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | FTC: Third Trimester | 184791.79 mL | Standard Deviation 56340.526 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | FTC: Week 6 Post-partum | 117384.90 mL | Standard Deviation 35385.941 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | FTC: Week 12 Post-partum | 117660.87 mL | Standard Deviation 33240.095 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | TAF: Second Trimester | 62333.17 mL | Standard Deviation 37242.307 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | TAF: Third Trimester | 53230.98 mL | Standard Deviation 16727.325 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | TAF: Week 6 Post-partum | 44440.06 mL | Standard Deviation 13678.515 |
| B/F/TAF | PK Parameter: Vz/F of BIC, FTC, and TAF | TAF: Week 12 Post-partum | 49837.70 mL | Standard Deviation 22019.454 |
Secondary
PK Parameter: λz of BIC, FTC, and TAF
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.
Time frame: 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
Population: Participants in the PK analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | TAF: Week 12 Post-partum | 1.954 1/h | Standard Deviation 0.4519 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | BIC: Second Trimester | 0.077 1/h | Standard Deviation 0.0231 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | BIC: Third Trimester | 0.068 1/h | Standard Deviation 0.0125 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | BIC: Week 6 Post-partum | 0.040 1/h | Standard Deviation 0.0098 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | BIC: Week 12 Post-partum | 0.043 1/h | Standard Deviation 0.0134 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | FTC: Second Trimester | 0.113 1/h | Standard Deviation 0.0142 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | FTC: Third Trimester | 0.112 1/h | Standard Deviation 0.0173 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | FTC: Week 6 Post-partum | 0.114 1/h | Standard Deviation 0.0151 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | FTC: Week 12 Post-partum | 0.120 1/h | Standard Deviation 0.0209 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | TAF: Second Trimester | 2.227 1/h | Standard Deviation 0.7128 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | TAF: Third Trimester | 2.550 1/h | Standard Deviation 0.7519 |
| B/F/TAF | PK Parameter: λz of BIC, FTC, and TAF | TAF: Week 6 Post-partum | 1.777 1/h | Standard Deviation 0.4685 |