Safety and Efficacy of Tenofovir DF in HIV-1 Infected Adolescents Failing Their Current Antiretroviral Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00352053
First received: July 13, 2006
Last updated: January 27, 2014
Last verified: January 2014
Results First Received: March 5, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Tenofovir DF
Drug: Placebo

  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
There were 17 sites in Brazil and 1 site in Panama. First participant was screened on 13 June 2006. Last participant was randomized on 12 March 2008. The last participant observation (LPO) for the primary endpoint analysis (Week 24) was 04 Sept 2008; LPO for the Week 48 analysis was 09 March 2009; LPO for Week 144 analysis was 29 September 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Three of the 90 participants who were randomized discontinued the study prior to the first dose of study drug due to withdrawal of consent (1 in the tenofovir DF group and 2 in the placebo group). A total of 87 participants received study drug (randomized and treated analysis set).

Reporting Groups
  Description
Tenofovir DF Double-blind tenofovir DF 300-mg tablets were administered during the double-blind treatment period (baseline to Week 48) with a genotype-guided optimized background regimen (OBR), defined as at least 3, but no more than 5 antiretroviral agents, not including tenofovir DF. Open-label tenofovir DF 300-mg tablets were administered during the extension phases.
Placebo Double-blind matching tenofovir DF placebo tablets were administered with a genotype-guided OBR to facilitate blinding during the double-blind treatment period.

Participant Flow for 3 periods

Period 1:   Randomized Phase (Week 48)
    Tenofovir DF     Placebo  
STARTED     45     42  
COMPLETED     27     29 [1]
NOT COMPLETED     18     13  
Unblinded for Virologic Failure                 14                 10  
Physician Decision                 2                 2  
Adverse Event                 1                 0  
Withdrawal by Subject                 0                 1  
Intolerance to Antiretroviral Regimen                 1                 0  
[1] 10 participants were unblinded for virologic failure and switched to TDF (open-label extension)

Period 2:   First Extension Phase (Weeks 48-144)
    Tenofovir DF     Placebo  
STARTED     24 [1]   36 [2]
COMPLETED     12     19  
NOT COMPLETED     12     17  
Physician Decision                 9                 13  
Lack of Efficacy                 1                 4  
Pregnancy                 1                 0  
Lost to Follow-up                 1                 0  
[1] Three participants completed the 48 week randomized phase and did not enroll in the extension phase.
[2] Three participants in the placebo group did not enroll in the first extension phase.

Period 3:   Second Extension Phase (Weeks 144-240)
    Tenofovir DF     Placebo  
STARTED     9 [1]   14 [2]
COMPLETED     0 [3]   0 [3]
NOT COMPLETED     9     14  
Study Ongoing                 7                 14  
Physician Decision                 1                 0  
Withdrawal by Subject                 1                 0  
[1] Three participants completed first extension phase and were not enrolled in second extension phase
[2] Five participants completed first extension phase and were not enrolled in second extension phase
[3] Study is ongoing, therefore no participants have completed the study.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Tenofovir DF Double-blind tenofovir DF 300-mg tablets were administered during the double-blind treatment period (baseline to Week 48) with a genotype-guided OBR, defined as at least 3, but no more than 5 antiretroviral agents, not including tenofovir DF.
Placebo Double-blind matching tenofovir DF placebo tablets were administered with a genotype-guided OBR to facilitate blinding during the double-blind treatment period. No placebo was used after Week 48.
Total Total of all reporting groups

Baseline Measures
    Tenofovir DF     Placebo     Total  
Number of Participants  
[units: participants]
  45     42     87  
Age  
[units: participants]
     
<=18 years     45     42     87  
Between 18 and 65 years     0     0     0  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  14  ± 1.5     14  ± 1.5     14  ± 1.5  
Gender  
[units: participants]
     
Female     24     25     49  
Male     21     17     38  
Ethnicity (NIH/OMB)  
[units: Participants]
     
Hispanic or Latino     45     42     87  
Not Hispanic or Latino     0     0     0  
Unknown or Not Reported     0     0     0  
Race/Ethnicity, Customized  
[units: Participants]
     
White     23     22     45  
Black or African Heritage     14     11     25  
Mulatto     4     4     8  
Mixed Race     1     2     3  
Indian Descendant     1     1     2  
Mestizo     0     2     2  
Black and White Race     1     0     1  
South American Indian     1     0     1  
Region of Enrollment  
[units: participants]
     
Panama     2     2     4  
Brazil     43     40     83  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation
  18.72  ± 2.304     19.99  ± 3.238     19.33  ± 2.849  
CD4 Cell Count  
[units: cells/mm^3]
Mean ± Standard Deviation
  390  ± 244.0     357  ± 200.8     374  ± 223.5  
CD4 Percentage [1]
[units: Percentage of CD4 lymphocytes]
Mean ± Standard Deviation
  17.8  ± 9.70     17.6  ± 8.31     17.7  ± 9.00  
Height  
[units: cm]
Mean ± Standard Deviation
  155.84  ± 10.071     156.05  ± 8.569     155.94  ± 9.322  
Human Immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA)  
[units: log10 copies/mL]
Mean ± Standard Deviation
  4.71  ± 0.723     4.56  ± 0.746     4.64  ± 0.734  
Weight  
[units: kg]
Mean ± Standard Deviation
  45.84  ± 9.639     49.09  ± 11.342     47.41  ± 10.561  
[1] CD4 percentage is the percentage of total lymphocytes that are CD4 cells.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA   [ Time Frame: Baseline to 24 Weeks ]

2.  Secondary:   Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA   [ Time Frame: Baseline to 48 weeks ]

3.  Secondary:   Change From Baseline to Week 24 in HIV-1 RNA   [ Time Frame: Baseline to 24 weeks ]

4.  Secondary:   Change From Baseline to Week 48 in HIV-1 RNA   [ Time Frame: Baseline to 48 weeks ]

5.  Secondary:   Change From Baseline to Week 96 in HIV-1 RNA   [ Time Frame: Baseline to 96 weeks ]

6.  Secondary:   Change From Baseline to Week 144 in HIV-1 RNA   [ Time Frame: Baseline to 144 weeks ]

7.  Secondary:   Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count   [ Time Frame: Baseline to 24 weeks ]

8.  Secondary:   Change From Baseline to Week 48 in CD4 Count   [ Time Frame: Baseline to 48 weeks ]

9.  Secondary:   Change From Baseline to Week 96 in CD4 Count   [ Time Frame: Baseline to 96 weeks ]

10.  Secondary:   Change From Baseline to Week 144 in CD4 Count   [ Time Frame: Baseline to 144 weeks ]

11.  Secondary:   Change From Baseline to Week 24 in CD4 Percentage   [ Time Frame: Baseline to 24 weeks ]

12.  Secondary:   Change From Baseline to Week 48 in CD4 Percentage   [ Time Frame: Baseline to 48 weeks ]

13.  Secondary:   Change From Baseline to Week 96 in CD4 Percentage   [ Time Frame: Baseline to 96 weeks ]

14.  Secondary:   Change From Baseline to Week 144 in CD4 Percentage   [ Time Frame: Baseline to 144 weeks ]

15.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 24   [ Time Frame: Baseline to 24 weeks ]

16.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 48   [ Time Frame: Baseline to 48 weeks ]

17.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 96   [ Time Frame: Baseline to 96 weeks ]

18.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 144   [ Time Frame: Baseline to 144 weeks ]

19.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24   [ Time Frame: Week 24 ]

20.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48   [ Time Frame: Week 48 ]

21.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96   [ Time Frame: Week 96 ]

22.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144   [ Time Frame: Week 144 ]

23.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24   [ Time Frame: Week 24 ]

24.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48   [ Time Frame: Week 48 ]

25.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96   [ Time Frame: Week 96 ]

26.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144   [ Time Frame: Week 144 ]

27.  Secondary:   Percentage of Participants With Virologic Failure at Week 48   [ Time Frame: 48 weeks ]

28.  Secondary:   Change From Baseline to Week 192 in HIV-1 RNA   [ Time Frame: Baseline to 192 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

29.  Secondary:   Change From Baseline to Week 240 in HIV-1 RNA   [ Time Frame: Baseline to 240 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

30.  Secondary:   Change From Baseline to Week 288 in HIV-1 RNA   [ Time Frame: Baseline to 288 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

31.  Secondary:   Change From Baseline to Week 336 in HIV-1 RNA   [ Time Frame: Baseline to 336 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

32.  Secondary:   Change From Baseline to Week 192 in CD4 Count   [ Time Frame: Baseline to 192 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

33.  Secondary:   Change From Baseline to Week 240 in CD4 Count   [ Time Frame: Baseline to 240 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

34.  Secondary:   Change From Baseline to Week 288 in CD4 Count   [ Time Frame: Baseline to 288 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

35.  Secondary:   Change From Baseline to Week 336 in CD4 Count   [ Time Frame: Baseline to 336 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

36.  Secondary:   Change From Baseline to Week 192 in CD4 Percentage   [ Time Frame: Baseline to 192 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

37.  Secondary:   Change From Baseline to Week 240 in CD4 Percentage   [ Time Frame: Baseline to 240 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

38.  Secondary:   Change From Baseline to Week 288 in CD4 Percentage   [ Time Frame: Baseline to 288 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

39.  Secondary:   Change From Baseline in Week 336 in CD4 Percentage   [ Time Frame: Baseline to 336 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

40.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 192   [ Time Frame: Baseline to 192 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

41.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 240   [ Time Frame: Baseline to 240 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

42.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0log10 Copies/mL From Baseline to Week 288   [ Time Frame: Baseline to 288 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

43.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0log10 Copies/mL From Baseline to Week 336   [ Time Frame: Baseline to 336 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

44.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192   [ Time Frame: Week 192 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

45.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240   [ Time Frame: Week 240 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

46.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288   [ Time Frame: Week 288 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

47.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 336   [ Time Frame: Week 336 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

48.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192   [ Time Frame: Week 192 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

49.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240   [ Time Frame: Week 240 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

50.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288   [ Time Frame: Week 288 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

51.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 336   [ Time Frame: Week 336 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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.


  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.


Results Point of Contact:  
Name/Title: Dara Wambach, MA, Associate Director, Regulatory Affairs
Organization: Gilead Sciences
phone: 650 522 5163
e-mail: Dara.Wambach@gilead.com


No publications provided


Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00352053     History of Changes
Other Study ID Numbers: GS-US-104-0321
Study First Received: July 13, 2006
Results First Received: March 5, 2010
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration
Brazil: Ministry of Health
Panama: Commemorative Institute GORGAS of Studies of Health