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Pharmacokinetics of Atazanavir/Ritonavir in HIV-1 Infected Pregnant Women

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00326716
First received: May 15, 2006
Last updated: November 4, 2011
Last verified: November 2011
History of Changes
Results First Received: January 5, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infection
Intervention: Drug: Atazanavir + Ritonavir + Combivir

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Pregnant participants were enrolled at 6 sites: United States (2), South Africa (3), and Puerto Rico (1).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 69 enrolled participants, 28 mothers were not treated. Failure to continue to meet enrollment criteria resulting in discontinuation in 24/28 participants and 4 were not treated: 1 poor/no compliance, 1 met exclusion criteria, 1 was ARV naive subject with HIV RNA < 400 c/mL, and 1 was unable to comply with study procedures.

Reporting Groups
  Description
Mother ATV 300 mg / RTV 100 mg Mothers receiving atazanavir (ATV) / ritonavir (RTV) 300/100 mg once daily (QD) + lamivudine (ZDV) / zidovudine (3TC) 300/150 mg twice daily (BID) during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mother ATV 400 mg / RTV 100 mg Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Infants ATV 300 mg / RTV 100 mg Infants born to mothers receiving treatment with ATV 300 mg / RTV 100 mg during the third trimester of pregnancy.
Infants ATV 400 mg / RTV 100 mg Infants born to mothers receiving treatment with ATV 400 mg / RTV 100 mg during the third trimester of pregnancy.

Participant Flow for 2 periods

 Period 1:   Pre-Natal Mothers
    Mother ATV 300 mg / RTV 100 mg     Mother ATV 400 mg / RTV 100 mg     Infants ATV 300 mg / RTV 100 mg     Infants ATV 400 mg / RTV 100 mg  
STARTED     20     21     0     0  
COMPLETED     19 [1]   19 [1]   0 [2]   0 [2]
NOT COMPLETED     1     2     0     0  
Discontinued ATV Before Delivery                 1                 2                 0                 0  
[1] Completion was defined as completing the study.
[2] Completion was defined as completing all follow up visits through 6 months.

Period 2:   Infants
    Mother ATV 300 mg / RTV 100 mg     Mother ATV 400 mg / RTV 100 mg     Infants ATV 300 mg / RTV 100 mg     Infants ATV 400 mg / RTV 100 mg  
STARTED     0     0     20 [1]   20 [2]
COMPLETED     0     0     20     20  
NOT COMPLETED     0     0     0     0  
[1] All infants were followed.
[2] All infants were followed. One mother withdrew consent pre-delivery and her infant was not followed.



  Baseline Characteristics
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Reporting Groups
  Description
Mother ATV 300 mg / RTV 100 mg Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mother ATV 400 mg / RTV 100 mg Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Total Total of all reporting groups

Baseline Measures
    Mother ATV 300 mg / RTV 100 mg     Mother ATV 400 mg / RTV 100 mg     Total  
Number of Participants  
[units: participants]
 		  20     21     41  
Age  
[units: participants]
 		     
<=18 years     0     0     0  
Between 18 and 65 years     20     21     41  
>=65 years     0     0     0  
Age  
[units: Years]
Median ( Full Range ) 		  29  
  ( 21 to 38 )   		  28  
  ( 19 to 37 )   		  28  
  ( 19 to 38 )  
Gender  
[units: participants]
 		     
Female     20     21     41  
Male     0     0     0  
Race (NIH/OMB)  
[units: Participants]
 		     
American Indian or Alaska Native     0     0     0  
Asian     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     17     19     36  
White     3     1     4  
More than one race     0     1     1  
Unknown or Not Reported     0     0     0  
Region of Enrollment  
[units: participants]
 		     
North America     6     6     12  
Africa     14     15     29  
HIV RNA Distribution at Baseline  
[units: c/mL]
 		     
<50     3     1     4  
50 to < 30,000     13     13     26  
30,000 to < 100,000     3     6     9  
>= 100,000     1     1     2  
Infant Gestational Age at Delivery  
[units: Weeks]
Median ( Full Range ) 		  38  
  ( 35 to 40 )   		  38  
  ( 35 to 41 )   		  38  
  ( 35 to 41 )  



  Outcome Measures
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1.  Primary:   Infant Gestational Age at Delivery   [ Time Frame: At the time of delivery ]
  Show Outcome Measure 1

2.  Primary:   Infant Gender   [ Time Frame: At the time of delivery ]
  Show Outcome Measure 2

3.  Primary:   Infant Race   [ Time Frame: At the time of delivery ]
  Show Outcome Measure 3

4.  Primary:   Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval   [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]
  Show Outcome Measure 4

5.  Primary:   Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval   [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]
  Show Outcome Measure 5

6.  Primary:   Mean ATV Area Under the Concentration Curve (AUC TAU)   [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]
  Show Outcome Measure 6

7.  Primary:   Mean RTV Area Under the Concentration Curve (AUC TAU)   [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]
  Show Outcome Measure 7

8.  Primary:   Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose   [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose. ]
  Show Outcome Measure 8

9.  Primary:   Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose   [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose. ]
  Show Outcome Measure 9

10.  Primary:   Mean ATV Terminal Elimination Half Life (T 1/2)   [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]
  Show Outcome Measure 10

11.  Primary:   Mean RTV Terminal Elimination Half Life (T 1/2)   [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]
  Show Outcome Measure 11

12.  Primary:   Mean ATV Time of Maximum Observed Plasma Concentration (Tmax)   [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]
  Show Outcome Measure 12

13.  Primary:   Mean RTV Time of Maximum Observed Plasma Concentration (Tmax)   [ Time Frame: Pregnancy Weeks 12 to 28, Weeks 28 to 36, and 4-6 Weeks Postpartum ]
  Show Outcome Measure 13

14.  Secondary:   Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery   [ Time Frame: Day of Delivery ± 2 Days ]
  Show Outcome Measure 14

15.  Secondary:   Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level   [ Time Frame: Baseline, Day of Delivery ± 2 Days ]
  Show Outcome Measure 15

16.  Secondary:   Mean HIV RNA Level at Baseline   [ Time Frame: Baseline ]
  Show Outcome Measure 16

17.  Secondary:   Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count   [ Time Frame: Baseline, Day of Delivery ± 2 Days ]
  Show Outcome Measure 17

18.  Secondary:   Mean CD4 Cell Count at Baseline   [ Time Frame: Baseline ]
  Show Outcome Measure 18

19.  Secondary:   Infant HIV Status   [ Time Frame: Birth Through 6 Months on Study ]
  Show Outcome Measure 19

20.  Secondary:   Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)   [ Time Frame: During study period and 30 days post-study. ]
  Show Outcome Measure 20

21.  Secondary:   Number of Participants With Grade 2 to Grade 4 AEs and SAEs   [ Time Frame: During Study Period and 30 Days Post-Study. ]
  Show Outcome Measure 21

22.  Secondary:   SAEs in Enrolled Mothers   [ Time Frame: During Study Period and 30 Days Post-Study. ]
  Show Outcome Measure 22

23.  Secondary:   SAEs in Enrolled Infants   [ Time Frame: Birth Through Week 16 of Life ]
  Show Outcome Measure 23

24.  Secondary:   Mean Atazanavir Maternal Plasma Concentration and Neonatal Cord Blood Concentration   [ Time Frame: At Time of Delivery ]
  Show Outcome Measure 24

25.  Secondary:   Median Infant Total Bilirubin Level   [ Time Frame: Birth (Day 1), Day 3, Day 5, and Day 7 of Life ]
  Show Outcome Measure 25

26.  Secondary:   Mean Atazanavir Plasma Protein Binding   [ Time Frame: Pregnancy Weeks 28 to Delivery at 3 Hours Postdose and 24 Hours Postdose, and Time of Delivery ]
  Show Outcome Measure 26

27.  Secondary:   Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose   [ Time Frame: Study Week 2, Pregnancy Weeks 20 to Weeks 28, Pregnancy Weeks 28 to Delivery, Week 2 Postpartum, Week 4 Postpartum ]
  Show Outcome Measure 27


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: clinical.trials@bms.com


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00326716     History of Changes
Other Study ID Numbers: AI424-182
Study First Received: May 15, 2006
Results First Received: January 5, 2011
Last Updated: November 4, 2011
Health Authority: United States: Food and Drug Administration
Republic of South Africa: National Ministry of Health