Pharmacokinetics of Atazanavir/Ritonavir in HIV-1 Infected Pregnant Women
- Registration Number
- NCT00326716
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
To determine what dosing regimen of atazanavir (ATV) / ritonavir (RTV) produces adequate drug exposure during pregnancy compared to drug exposure in historical data in human immunodeficiency virus (HIV) infected participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 69
- HIV-infected pregnant women
- > 18 years of age
- Between week 12 and 32 gestation
- CD4 > 200 cells/mm³
- Treatment-naive with HIV RNA > 400 c/mL, on HAART with HIV RNA <50 c/mL, or previously treated with ATV (< 3 weeks) with HIV RNA>400 c/mL
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Atazanavir + Ritonavir + Combivir -
- Primary Outcome Measures
Name Time Method Infant Gestational Age at Delivery At the time of delivery Infant Gender At the time of delivery Infant Race At the time of delivery Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum Cmax = maximum observed plasma concentration of atazanavir at specified time points.
Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum Cmax = maximum observed plasma concentration of ritonavir at specified time points.
Mean ATV Area Under the Concentration Curve (AUC TAU) Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum AUC = area under the concentration curve (AUC \[TAU\]) of atazanavir in one dosing interval from time zero to 24 hours.
Mean RTV Area Under the Concentration Curve (AUC TAU) Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum AUC = area under the concentration curve (AUC \[TAU\]) of ritonavir in one dosing interval.
Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose. Cmin = plasma concentration 24 hours post dose of atazanavir at specified time points.
Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose. Cmin = plasma concentration 24 hours post dose of ritonavir at specified time points.
Mean ATV Terminal Elimination Half Life (T 1/2) Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum T 1/2 = terminal elimination half life of atazanavir at specified time points.
Mean RTV Terminal Elimination Half Life (T 1/2) Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum T 1/2 = terminal elimination half life of ritonavir at specified time points.
Mean ATV Time of Maximum Observed Plasma Concentration (Tmax) Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum Tmax = time to reach maximum observed plasma concentration of atazanavir at specified time points.
Mean RTV Time of Maximum Observed Plasma Concentration (Tmax) Pregnancy Weeks 12 to 28, Weeks 28 to 36, and 4-6 Weeks Postpartum Tmax = time to reach the maximum observed plasma concentration of ritonavir at specified time points.
- Secondary Outcome Measures
Name Time Method Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery Day of Delivery ± 2 Days The maternal HIV RNA level is assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5.
Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level Baseline, Day of Delivery ± 2 Days The maternal HIV RNA level was determined at baseline and the day of delivery ± 2 days using VR-OC. The maternal HIV RNA level is assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5.
Mean HIV RNA Level at Baseline Baseline Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count Baseline, Day of Delivery ± 2 Days The median CD4 cell count change from baseline was calculated for all treated mothers at the time of delivery ± 2 days. Maternal CD4 cell counts were assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5.
Mean CD4 Cell Count at Baseline Baseline Infant HIV Status Birth Through 6 Months on Study The neonatal HIV-1 status are assessed by the Roche Amplicor HIV-1 DNA Assay Version 1.5 (Roche Molecular Systems).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During study period and 30 days post-study. AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE =any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Number of Participants With Grade 2 to Grade 4 AEs and SAEs During Study Period and 30 Days Post-Study. AEs and SAEs considered possibly, probably, or certainly related to study treatment, were graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). Hyperbilirubinemia (Grade 1=1.1 to 1.5 upper limit of normal \[ULN\] \[mild\], Grade 2=1.6 to 2.5 ULN \[moderate\], Grade 3=2.6 to 5.0 ULN \[severe\], Grade 4= \> 5.0 ULN \[potentially life threatening\]).
SAEs in Enrolled Mothers During Study Period and 30 Days Post-Study. SAEs were evaluated for all treated and untreated participants. An SAE was defined as an untoward medical occurrence that results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event); might have caused death if it were more severe, required inpatient hospitalization or prolongation of existing hospitalization, in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, an important medical event that required intervention to prevent serious outcomes.
SAEs in Enrolled Infants Birth Through Week 16 of Life SAEs were evaluated for all treated and untreated participants. An SAE was defined as an untoward medical occurrence that results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event); might have caused death if it were more severe, required inpatient hospitalization or prolongation of existing hospitalization, in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, an important medical event that required intervention to prevent serious outcomes.
Mean Atazanavir Maternal Plasma Concentration and Neonatal Cord Blood Concentration At Time of Delivery Mean atazanavir maternal plasma concentration and neonatal cord blood concentration as measured at the time of delivery.
Median Infant Total Bilirubin Level Birth (Day 1), Day 3, Day 5, and Day 7 of Life Median infant total bilirubin level as measured at specified time points.
Mean Atazanavir Plasma Protein Binding Pregnancy Weeks 28 to Delivery at 3 Hours Postdose and 24 Hours Postdose, and Time of Delivery Atazanavir Plasma Protein Binding Percentage measured at specified time points.
Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose Study Week 2, Pregnancy Weeks 20 to Weeks 28, Pregnancy Weeks 28 to Delivery, Week 2 Postpartum, Week 4 Postpartum The MACS was administered to evaluate participant adherence to each drug and the adherence to the regimen. The MACS adherence questionnaire asks patients how many medication doses they missed during the previous day, 2 days, 3 days and 4 days. Drug-specific questions included adherence with dose and frequency. Adherence was defined as taking all doses and numbers of pills as prescribed for each medication. This strict adherence cut-off was based on the guidelines stating that anything less than excellent adherence may result in a virus breakthrough and development of resistance.
Trial Locations
- Locations (3)
Triple O Medical Services, P.A.
🇺🇸West Palm Beach, Florida, United States
Women's Hospital Of Texas
🇺🇸Houston, Texas, United States
Local Institution
🇿🇦Westdene, Gauteng, South Africa