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Extended Safety Study of Tenofovir Disoproxil Fumarate (TDF) Among HIV-1 Negative Men

This study has been completed.
Sponsor:
Collaborators:
San Francisco Department of Public Health
AIDS Research Consortium of Atlanta
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00131677
First received: August 17, 2005
Last updated: January 22, 2014
Last verified: August 2013
Results First Received: August 8, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Condition: HIV Infection
Interventions: Drug: tenofovir disoproxil fumarate
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

Recruitment began in 1/2005 and was completed in 7/2007. Participant follow-up was completed in July 2009.

Participants were recruited from:

San Francisco Dept. of Public Health AIDS Research Consortium of Atlanta Fenway Health


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After an initial screening visit, participants were required to meet all enrollment criteria again at the enrollment visit.

Reporting Groups
  Description
Tenofovir Disoproxil Fumarate Participants received TDF 300mg orally daily for 24 months (immediate arm) or 15 months (delayed arm).
Placebo Participants received matching placebo, to be taken daily.

Participant Flow:   Overall Study
    Tenofovir Disoproxil Fumarate     Placebo  
STARTED     201 [1]   199 [2]
COMPLETED     171     160  
NOT COMPLETED     30     39  
[1] 201 randomized to active drug; 101 to start immediately and 100 after a 9 month delay.
[2] 199 randomized to placebo; 99 to start immediately and 100 after a 9 month delay.



  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.
400 participants enrolled (200 in San Francisco, 121 in Atlanta, and 79 in Boston). 201 were randomized to TDF and 199 to placebo. Participants were distributed similarly in terms of age, ethnicity, education, no. male partners in previous 3 mo., and no. of unprotected anal sexual contacts within the previous 3 mo.

Reporting Groups
  Description
Tenofovir Disoproxil Fumarate Active arm: assigned to take TDF, 300mg po daily.
Placebo Placebo arm--received matching placebo
Total Total of all reporting groups

Baseline Measures
    Tenofovir Disoproxil Fumarate     Placebo     Total  
Number of Participants  
[units: participants]
  201     199     400  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     201     199     400  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  38.7  ± 9.3     36.7  ± 11.0     37.7  ± 10.2  
Gender  
[units: participants]
     
Female     0     0     0  
Male     201     199     400  
Region of Enrollment  
[units: participants]
     
United States     201     199     400  



  Outcome Measures
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1.  Primary:   Clinical Safety--Creatinine Elevations   [ Time Frame: 24 months (immediate arm) and 15 months (delayed arm) ]

Measure Type Primary
Measure Title Clinical Safety--Creatinine Elevations
Measure Description Grade 3 or 4 Creatinine elevations (per National Institutes of Health Division of AIDS toxicity scale)
Time Frame 24 months (immediate arm) and 15 months (delayed arm)  
Safety Issue Yes  

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.
For biomedical outcomes, a treatment emergent cohort was defined. Participants entered the TE cohort with first dispense and exited with the first occurrence of: (1) completion of follow-up, (2) 30 days after permanent drug interruption, or (3) 30 days after last visit. For delayed arm participants,time before initiation of drug was excluded.

Reporting Groups
  Description
Tenofovir Disoproxil Fumarate TDF, 300 mg orally daily
Placebo Matching placebo daily

Measured Values
    Tenofovir Disoproxil Fumarate     Placebo  
Number of Participants Analyzed  
[units: participants]
  186     187  
Clinical Safety--Creatinine Elevations  
[units: Participants]
  0     0  

No statistical analysis provided for Clinical Safety--Creatinine Elevations



2.  Primary:   Clinical Safety--Hypophosphatemia   [ Time Frame: 24 months (immediate arm), 15 months (delayed arm) ]

Measure Type Primary
Measure Title Clinical Safety--Hypophosphatemia
Measure Description Grade 3 or 4 hypophosphatemia (per National Institutes of Health Division of AIDS toxicity scale)
Time Frame 24 months (immediate arm), 15 months (delayed arm)  
Safety Issue Yes  

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.
For biomedical outcomes, a treatment emergent cohort was defined which included only those participants who received study drug.

Reporting Groups
  Description
Tenofovir Disoproxil Fumarate Active arm: assigned to take TDF, 300mg po daily.
Placebo Placebo arm--received matching placebo

Measured Values
    Tenofovir Disoproxil Fumarate     Placebo  
Number of Participants Analyzed  
[units: participants]
  186     187  
Clinical Safety--Hypophosphatemia  
[units: participants]
  1     5  

No statistical analysis provided for Clinical Safety--Hypophosphatemia



3.  Secondary:   Number of Breakthrough HIV Infections   [ Time Frame: 24 months (immediate arm) and 15 months (delayed arm) ]

Measure Type Secondary
Measure Title Number of Breakthrough HIV Infections
Measure Description Number of participants with HIV seroconversions occuring while on study drug
Time Frame 24 months (immediate arm) and 15 months (delayed arm)  
Safety Issue Yes  

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.
For biomedical outcomes, a treatment emergent cohort was defined which included only those participants who received study drug.

Reporting Groups
  Description
Tenofovir Disoproxil Fumarate TDF, 300 mg orally daily.
Placebo Matching placebo daily

Measured Values
    Tenofovir Disoproxil Fumarate     Placebo  
Number of Participants Analyzed  
[units: participants]
  186     187  
Number of Breakthrough HIV Infections  
[units: participants]
  0     4  

No statistical analysis provided for Number of Breakthrough HIV Infections



4.  Secondary:   Adherence to Study Drug   [ Time Frame: 24 months (immediate arm) and 15 months (delayed arm) ]

Measure Type Secondary
Measure Title Adherence to Study Drug
Measure Description Estimated exposure to study drug (active and placebo) as assessed by Medication Event Monitoring System (MEMS) caps.
Time Frame 24 months (immediate arm) and 15 months (delayed arm)  
Safety Issue No  

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
Treatment Emergent Cohort Includes all who entered treatment emergent cohort (active and placebo arms)

Measured Values
    Treatment Emergent Cohort  
Number of Participants Analyzed  
[units: participants]
  373  
Adherence to Study Drug  
[units: percentage of doses]
  77  

No statistical analysis provided for Adherence to Study Drug



5.  Secondary:   Behavioral Safety--Unprotected Anal Sex (UAS)   [ Time Frame: Nine months ]

Measure Type Secondary
Measure Title Behavioral Safety--Unprotected Anal Sex (UAS)
Measure Description Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study.
Time Frame Nine months  
Safety Issue Yes  

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
All Enrolled Participants No text entered.

Measured Values
    All Enrolled Participants  
Number of Participants Analyzed  
[units: participants]
  400  
Behavioral Safety--Unprotected Anal Sex (UAS)  
[units: percentage of ppts reporting UAS]
  -9  

No statistical analysis provided for Behavioral Safety--Unprotected Anal Sex (UAS)



6.  Other Pre-specified:   >5% Bone Mineral Density Decline at Femoral Neck   [ Time Frame: 24 months (immediate arm), 15 months (delayed arm) ]

Measure Type Other Pre-specified
Measure Title >5% Bone Mineral Density Decline at Femoral Neck
Measure Description Percent of San Francisco participants in the TDF vs. placebo groups who were found to have >5% decline in Bone Mineral Density at the femoral neck.
Time Frame 24 months (immediate arm), 15 months (delayed arm)  
Safety Issue Yes  

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.
For biomedical outcomes, a treatment emergent cohort was defined which included only those participants who received study drug. In addition, this analysis population includes only those participants for whom bone density analyses were performed.

Reporting Groups
  Description
Tenofovir Disoproxil Fumarate Active arm: assigned to take TDF, 300mg po daily.
Placebo Placebo arm--received matching placebo

Measured Values
    Tenofovir Disoproxil Fumarate     Placebo  
Number of Participants Analyzed  
[units: participants]
  94     90  
>5% Bone Mineral Density Decline at Femoral Neck  
[units: percentage of participants]
  13     6  

No statistical analysis provided for >5% Bone Mineral Density Decline at Femoral Neck




  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
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: Taraz Samandari
Organization: Centers for Disease Control and Prevention (CDC)
phone: 404-639-1676
e-mail: tts0@cdc.gov


No publications provided by Centers for Disease Control and Prevention

Publications automatically indexed to this study:

Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT00131677     History of Changes
Other Study ID Numbers: CDC-NCHHSTP-4323
Study First Received: August 17, 2005
Results First Received: August 8, 2013
Last Updated: January 22, 2014
Health Authority: United States: Federal Government