NCT00326716

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
69

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jun 2006

Typical duration for phase_1

Geographic Reach
3 countries

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 15, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 17, 2006

Completed
15 days until next milestone

Study Start

First participant enrolled

June 1, 2006

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2009

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2009

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

April 7, 2011

Completed
Last Updated

November 16, 2011

Status Verified

November 1, 2011

Enrollment Period

2.6 years

First QC Date

May 15, 2006

Results QC Date

January 5, 2011

Last Update Submit

November 4, 2011

Conditions

HIV Infection

Keywords

HIV-1 infected pregnant women, either treatment naive or on ATV/RTV combined with ZDV/3TC

Outcome Measures

Primary Outcomes (13)

  • 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

    Cmax = maximum observed plasma concentration of atazanavir at specified time points.

    Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum

  • Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval

    Cmax = maximum observed plasma concentration of ritonavir at specified time points.

    Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum

  • Mean ATV Area Under the Concentration Curve (AUC TAU)

    AUC = area under the concentration curve (AUC \[TAU\]) of atazanavir in one dosing interval from time zero to 24 hours.

    Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum

  • Mean RTV Area Under the Concentration Curve (AUC TAU)

    AUC = area under the concentration curve (AUC \[TAU\]) of ritonavir in one dosing interval.

    Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum

  • Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose

    Cmin = plasma concentration 24 hours post dose of atazanavir at specified time points.

    Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose.

  • Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose

    Cmin = plasma concentration 24 hours post dose of ritonavir at specified time points.

    Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose.

  • Mean ATV Terminal Elimination Half Life (T 1/2)

    T 1/2 = terminal elimination half life of atazanavir at specified time points.

    Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum

  • Mean RTV Terminal Elimination Half Life (T 1/2)

    T 1/2 = terminal elimination half life of ritonavir at specified time points.

    Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum

  • Mean ATV Time of Maximum Observed Plasma Concentration (Tmax)

    Tmax = time to reach maximum observed plasma concentration of atazanavir at specified time points.

    Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum

  • Mean RTV Time of Maximum Observed Plasma Concentration (Tmax)

    Tmax = time to reach the maximum observed plasma concentration of ritonavir at specified time points.

    Pregnancy Weeks 12 to 28, Weeks 28 to 36, and 4-6 Weeks Postpartum

Secondary Outcomes (14)

  • Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery

    Day of Delivery ± 2 Days

  • Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level

    Baseline, Day of Delivery ± 2 Days

  • 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

  • Mean CD4 Cell Count at Baseline

    Baseline

  • +9 more secondary outcomes

Study Arms (1)

Treatment

EXPERIMENTAL
Drug: Atazanavir + Ritonavir + Combivir

Interventions

Atazanavir + Ritonavir + CombivirDRUG

Capsules, tablets, Oral, initially ATV 300 mg + RTV 100 mg + ZDV/3TC 300/150 mg, dose escalated to ATV 400 mg + RTV 100 mg + ZDV/3TC 300/150 mg, ATV and RTV once daily, lamivudine (ZDV) / zidovudine (3TC) twice daily (BID), up to 36 weeks

Also known as: Reyataz, BMS-232632
Treatment

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Triple O Medical Services, P.A.

West Palm Beach, Florida, 33401, United States

Location

Women's Hospital Of Texas

Houston, Texas, 77054, United States

Location

Local Institution

San Juan, 00936, Puerto Rico

Location

Local Institution

Soweto, Gauteng, 2001, South Africa

Location

Local Institution

Sunnyside, Gauteng, 0002, South Africa

Location

Local Institution

Westdene, Gauteng, 2092, South Africa

Location

Related Publications (3)

  • 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.

    PMID: 25529885DERIVED

  • 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.

    PMID: 23782005DERIVED

  • 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.

    PMID: 21569187DERIVED

Related Links

MeSH Terms

Conditions

HIV Infections

Interventions

Atazanavir SulfateRitonavirlamivudine, zidovudine drug combination

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

PyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsOligopeptidesPeptidesAmino Acids, Peptides, and ProteinsThiazolesSulfur CompoundsOrganic ChemicalsAzoles

Results Point of Contact

Title
BMS Study Director
Organization
Bristol-Myers Squibb
clinical.trials@bms.com

Study Officials

  • Bristol-Myers Squibb

    Bristol-Myers Squibb

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 15, 2006

First Posted

May 17, 2006

Study Start

June 1, 2006

Primary Completion

January 1, 2009

Study Completion

August 1, 2009

Last Updated

November 16, 2011

Results First Posted

April 7, 2011

Record last verified: 2011-11

Locations

US(2)ZA(3)PR(1)