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: June 15, 2015
Last verified: June 2015
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
  Hide Participant Flow

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. The last study visit occurred on 19 December 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
123 participants were screened.

Reporting Groups
  Description
Tenofovir DF Tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg tablets plus a genotype-guided optimized background regimen (OBR; 3 minimum (min.)/5 maximum (max.) antiretroviral agents (ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.
Placebo Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.

Participant Flow for 4 periods

Period 1:   Double-Blind Phase (Through Week 48)
    Tenofovir DF     Placebo  
STARTED     45     42  
COMPLETED     27     29 [1]
NOT COMPLETED     18     13  
Virologic Failure                 14                 10  
Physician Decision                 2                 2  
Adverse Event                 1                 0  
Withdrawal by Subject                 0                 1  
Intolerance to Antiretroviral Regimen                 1                 0  
[1] The 10 participants discontinued for virologic failure enrolled early in the open-label extension.

Period 2:   First Extension Phase (Weeks 48-144)
    Tenofovir DF     Placebo  
STARTED     24 [1]   36 [1]
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] 3 participants completed the double-blind phase but did not enroll in the 1st extension phase.

Period 3:   Second Extension Phase (Weeks 144-240)
    Tenofovir DF     Placebo  
STARTED     9 [1]   14 [2]
COMPLETED     4     9  
NOT COMPLETED     5     5  
Physician Decision                 4                 4  
Withdrawal by Subject                 1                 1  
[1] 3 participants completed the 1st extension phase but did not enroll in the 2nd extension phase.
[2] 5 participants completed the 1st extension phase but did not enroll in the 2nd extension phase.

Period 4:   Third Extension Phase (Weeks 240-294)
    Tenofovir DF     Placebo  
STARTED     1 [1]   4 [2]
COMPLETED     0     2  
NOT COMPLETED     1     2  
Lack of Efficacy                 1                 1  
Withdrawal by Subject                 0                 1  
[1] 3 participants completed the 2nd extension phase but did not enroll in the 3rd extension phase.
[2] 5 participants completed the 2nd extension phase but did not enroll in the 3rd extension phase.



  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.
Safety Analysis Set: participants were randomized and received at least 1 dose of study medication.

Reporting Groups
  Description
Tenofovir DF TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.
Placebo Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.
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 192 in HIV-1 RNA   [ Time Frame: Baseline to 192 weeks ]

8.  Secondary:   Change From Baseline to Week 240 in HIV-1 RNA   [ Time Frame: Baseline to 240 weeks ]

9.  Secondary:   Change From Baseline to Week 288 in HIV-1 RNA   [ Time Frame: Baseline to 288 weeks ]

10.  Secondary:   Change From Baseline to Week 336 in HIV-1 RNA   [ Time Frame: Baseline to 336 weeks ]

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

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

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

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

15.  Secondary:   Change From Baseline to Week 192 in CD4 Count   [ Time Frame: Baseline to 192 weeks ]

16.  Secondary:   Change From Baseline to Week 240 in CD4 Count   [ Time Frame: Baseline to 240 weeks ]

17.  Secondary:   Change From Baseline to Week 288 in CD4 Count   [ Time Frame: Baseline to 288 weeks ]

18.  Secondary:   Change From Baseline to Week 336 in CD4 Count   [ Time Frame: Baseline to 336 weeks ]

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

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

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

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

23.  Secondary:   Change From Baseline to Week 192 in CD4 Percentage   [ Time Frame: Baseline to 192 weeks ]

24.  Secondary:   Change From Baseline to Week 240 in CD4 Percentage   [ Time Frame: Baseline to 240 weeks ]

25.  Secondary:   Change From Baseline to Week 288 in CD4 Percentage   [ Time Frame: Baseline to 288 weeks ]

26.  Secondary:   Change From Baseline to Week 336 in CD4 Percentage   [ Time Frame: Baseline to 336 weeks ]

27.  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 ]

28.  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 ]

29.  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 ]

30.  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 ]

31.  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 ]

32.  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 ]

33.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288   [ Time Frame: Baseline to 288 weeks ]

34.  Secondary:   Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 336   [ Time Frame: Baseline to 336 weeks ]

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

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

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

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

39.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192   [ Time Frame: Week 192 ]

40.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240   [ Time Frame: Week 240 ]

41.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288   [ Time Frame: Week 288 ]

42.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 336   [ Time Frame: Week 336 ]

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

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

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

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

47.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192   [ Time Frame: Week 192 ]

48.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240   [ Time Frame: Week 240 ]

49.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288   [ Time Frame: Week 288 ]

50.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 336   [ Time Frame: Week 336 ]

51.  Secondary:   Percentage of Participants With Virologic Failure Through Week 48   [ Time Frame: Up to 48 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
Participants left the study for a number of reasons (eg, turned 18 years old, switched to a different HIV treatment regimen), which led to small numbers of participants analyzed at later time points, and the study was concluded earlier than planned.


  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: Clinical Trial Disclosures
Organization: Gilead Sciences
e-mail: ClinicalTrialDisclosures@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: June 15, 2015
Health Authority: United States: Food and Drug Administration
Brazil: Ministry of Health
Panama: Commemorative Institute GORGAS of Studies of Health