Clinical trial NCT00326716: Pharmacokinetics of Atazanavir/Ritonavir in HIV-1 Infected Pregnant Women
Official title: A Study of the Pharmacokinetics of Atazanavir (ATV)/Ritonavir(RTV) Administered as Part of Highly Active Antiretroviral Therapy (HAART) in HIV-1 Infected Pregnant Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infection
Keywords: HIV-1 infected pregnant women, either treatment naive or on ATV/RTV combined with ZDV/3TC
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-05-17
Enrollment: 69
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Primary outcomes:
measure: Infant Gestational Age at Delivery
timeFrame: At the time of delivery
measure: Infant Gender
timeFrame: At the time of delivery
measure: Infant Race
timeFrame: At the time of delivery
measure: Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval
timeFrame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
measure: Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval
timeFrame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
measure: Mean ATV Area Under the Concentration Curve (AUC TAU)
timeFrame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
measure: Mean RTV Area Under the Concentration Curve (AUC TAU)
timeFrame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
measure: Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose
timeFrame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose.
measure: Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose
timeFrame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose.
measure: Mean ATV Terminal Elimination Half Life (T 1/2)
timeFrame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
measure: Mean RTV Terminal Elimination Half Life (T 1/2)
timeFrame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
measure: Mean ATV Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
measure: Mean RTV Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: Pregnancy Weeks 12 to 28, Weeks 28 to 36, and 4-6 Weeks Postpartum
Secondary outcomes:
measure: Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery
timeFrame: Day of Delivery ± 2 Days
measure: Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level
timeFrame: Baseline, Day of Delivery ± 2 Days
measure: Mean HIV RNA Level at Baseline
timeFrame: Baseline
measure: Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count
timeFrame: Baseline, Day of Delivery ± 2 Days
measure: Mean CD4 Cell Count at Baseline
timeFrame: Baseline
measure: Infant HIV Status
timeFrame: Birth Through 6 Months on Study
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: During study period and 30 days post-study.
measure: Number of Participants With Grade 2 to Grade 4 AEs and SAEs
timeFrame: During Study Period and 30 Days Post-Study.
measure: SAEs in Enrolled Mothers
timeFrame: During Study Period and 30 Days Post-Study.
measure: SAEs in Enrolled Infants
timeFrame: Birth Through Week 16 of Life
measure: Mean Atazanavir Maternal Plasma Concentration and Neonatal Cord Blood Concentration
timeFrame: At Time of Delivery
measure: Median Infant Total Bilirubin Level
timeFrame: Birth (Day 1), Day 3, Day 5, and Day 7 of Life
measure: Mean Atazanavir Plasma Protein Binding
timeFrame: Pregnancy Weeks 28 to Delivery at 3 Hours Postdose and 24 Hours Postdose, and Time of Delivery
measure: Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose
timeFrame: Study Week 2, Pregnancy Weeks 20 to Weeks 28, Pregnancy Weeks 28 to Delivery, Week 2 Postpartum, Week 4 Postpartum
Other outcomes:
Locations:
city: West Palm Beach
country: United States
facility: Triple O Medical Services, P.A.
state: Florida
city: Houston
country: United States
facility: Women's Hospital Of Texas
state: Texas
city: San Juan
country: Puerto Rico
facility: Local Institution
city: Soweto
country: South Africa
facility: Local Institution
state: Gauteng
city: Sunnyside
country: South Africa
facility: Local Institution
state: Gauteng
city: Westdene
country: South Africa
facility: Local Institution
state: Gauteng
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Xu XS, Rose A, Demers R, Eley T, Ryan J, Stouffer B, Cojocaru L, Arnold M. Quantitative determination of free/bound atazanavir via high-throughput equilibrium dialysis and LC-MS/MS, and the application in ex vivo samples. Bioanalysis. 2014;6(23):3169-82. doi: 10.4155/bio.14.251.
citation: Eley T, Huang SP, Conradie F, Zorrilla CD, Josipovic D, Botes M, Osiyemi O, Hardy H, Bertz R, McGrath D. Clinical and pharmacogenetic factors affecting neonatal bilirubinemia following atazanavir treatment of mothers during pregnancy. AIDS Res Hum Retroviruses. 2013 Oct;29(10):1287-92. doi: 10.1089/AID.2013.0002. Epub 2013 Jul 19.
citation: Conradie F, Zorrilla C, Josipovic D, Botes M, Osiyemi O, Vandeloise E, Eley T, Child M, Bertz R, Hu W, Wirtz V, McGrath D. Safety and exposure of once-daily ritonavir-boosted atazanavir in HIV-infected pregnant women. HIV Med. 2011 Oct;12(9):570-9. doi: 10.1111/j.1468-1293.2011.00927.x. Epub 2011 May 16.