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

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ClinicalTrials.gov Identifier: NCT00131677
Recruitment Status : Completed
First Posted : August 19, 2005
Results First Posted : March 10, 2014
Last Update Posted : March 10, 2014
Sponsor:
Collaborators:
San Francisco Department of Public Health
AIDS Research Consortium of Atlanta
Information provided by (Responsible Party):
Centers for Disease Control and Prevention

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition HIV Infection
Interventions Drug: tenofovir disoproxil fumarate
Drug: placebo
Enrollment 400
Recruitment Details

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 After an initial screening visit, participants were required to meet all enrollment criteria again at the enrollment visit.
Arm/Group Title Tenofovir Disoproxil Fumarate Placebo
Hide Arm/Group Description Participants received TDF 300mg orally daily for 24 months (immediate arm) or 15 months (delayed arm). Participants received matching placebo, to be taken daily.
Period Title: Overall Study
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.
Arm/Group Title Tenofovir Disoproxil Fumarate Placebo Total
Hide Arm/Group Description Active arm: assigned to take TDF, 300mg po daily. Placebo arm--received matching placebo Total of all reporting groups
Overall Number of Baseline Participants 201 199 400
Hide Baseline Analysis Population Description
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.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 199 participants 400 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
201
 100.0%
199
 100.0%
400
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 199 participants 400 participants
38.7  (9.3) 36.7  (11.0) 37.7  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 199 participants 400 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
201
 100.0%
199
 100.0%
400
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 201 participants 199 participants 400 participants
201 199 400
1.Primary Outcome
Title Clinical Safety--Creatinine Elevations
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tenofovir Disoproxil Fumarate Placebo
Hide Arm/Group Description:
TDF, 300 mg orally daily
Matching placebo daily
Overall Number of Participants Analyzed 186 187
Measure Type: Number
Unit of Measure: Participants
0 0
2.Primary Outcome
Title Clinical Safety--Hypophosphatemia
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
For biomedical outcomes, a treatment emergent cohort was defined which included only those participants who received study drug.
Arm/Group Title Tenofovir Disoproxil Fumarate Placebo
Hide Arm/Group Description:
Active arm: assigned to take TDF, 300mg po daily.
Placebo arm--received matching placebo
Overall Number of Participants Analyzed 186 187
Measure Type: Number
Unit of Measure: participants
1 5
3.Secondary Outcome
Title Number of Breakthrough HIV Infections
Hide Description Number of participants with HIV seroconversions occuring while on study drug
Time Frame 24 months (immediate arm) and 15 months (delayed arm)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
For biomedical outcomes, a treatment emergent cohort was defined which included only those participants who received study drug.
Arm/Group Title Tenofovir Disoproxil Fumarate Placebo
Hide Arm/Group Description:
TDF, 300 mg orally daily.
Matching placebo daily
Overall Number of Participants Analyzed 186 187
Measure Type: Number
Unit of Measure: participants
0 4
4.Secondary Outcome
Title Adherence to Study Drug
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Emergent Cohort
Hide Arm/Group Description:
Includes all who entered treatment emergent cohort (active and placebo arms)
Overall Number of Participants Analyzed 373
Measure Type: Number
Unit of Measure: percentage of doses
77
5.Secondary Outcome
Title Behavioral Safety--Unprotected Anal Sex (UAS)
Hide Description Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study.
Time Frame Nine months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Enrolled Participants
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 400
Measure Type: Number
Unit of Measure: percentage of ppts reporting UAS
-9
6.Other Pre-specified Outcome
Title >5% Bone Mineral Density Decline at Femoral Neck
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Tenofovir Disoproxil Fumarate Placebo
Hide Arm/Group Description:
Active arm: assigned to take TDF, 300mg po daily.
Placebo arm--received matching placebo
Overall Number of Participants Analyzed 94 90
Measure Type: Number
Unit of Measure: percentage of participants
13 6
Time Frame Maximum time period on drug of 24 months for immediate arm participants and 15 months for delayed arm participants.
Adverse Event Reporting Description Treatment emergent cohort: participants enter cohort when study drug is initiated, and exit at the first occurence of one of these events: 1) completion of study visits, 2)30 days after loss to follow up, or 3)30 days after start of permanent drug interruption.
 
Arm/Group Title Tenofovir Disoproxil Fumarate Placebo
Hide Arm/Group Description Active arm: assigned to take TDF, 300mg po daily. Matching placebo daily
All-Cause Mortality
Tenofovir Disoproxil Fumarate Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Tenofovir Disoproxil Fumarate Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/186 (5.38%)      8/187 (4.28%)    
Cardiac disorders     
Atrial fibrillation  1/186 (0.54%)  1 0/187 (0.00%)  0
Coronary artery disease  0/186 (0.00%)  0 1/187 (0.53%)  1
Gastrointestinal disorders     
Gastrointestinal ulcer haemorrhage  1/186 (0.54%)  1 0/187 (0.00%)  0
General disorders     
Pyrexia  0/186 (0.00%)  0 1/187 (0.53%)  1
Infections and infestations     
Appendicitis  1/186 (0.54%)  1 1/187 (0.53%)  1
Appendicitis perforated  1/186 (0.54%)  1 0/187 (0.00%)  0
Injury, poisoning and procedural complications     
Seroma  1/186 (0.54%)  1 0/187 (0.00%)  0
Spinal fracture  1/186 (0.54%)  1 0/187 (0.00%)  0
Injury  0/186 (0.00%)  0 1/187 (0.53%)  1
Poisoning  1/186 (0.54%)  1 0/187 (0.00%)  0
Investigations     
Blood phosphorus decreased  0/186 (0.00%)  0 1/187 (0.53%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer  1/186 (0.54%)  1 1/187 (0.53%)  1
Colon cancer  1/186 (0.54%)  1 0/187 (0.00%)  0
Psychiatric disorders     
Depression  1/186 (0.54%)  4 2/187 (1.07%)  2
Suicide attempt  0/186 (0.00%)  0 1/187 (0.53%)  1
Suicidal ideation  0/186 (0.00%)  0 2/187 (1.07%)  2
Mania  1/186 (0.54%)  1 0/187 (0.00%)  0
Renal and urinary disorders     
Urinary retention  0/186 (0.00%)  0 1/187 (0.53%)  1
Respiratory, thoracic and mediastinal disorders     
Pulmonary edema  1/186 (0.54%)  3 0/187 (0.00%)  0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tenofovir Disoproxil Fumarate Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   149/186 (80.11%)      146/187 (78.07%)    
Gastrointestinal disorders     
Diarrhea  33/186 (17.74%)  42 45/187 (24.06%)  57
Flatulence  18/186 (9.68%)  21 18/187 (9.63%)  22
Nausea  20/186 (10.75%)  27 12/187 (6.42%)  13
General disorders     
Fatigue  17/186 (9.14%)  24 15/187 (8.02%)  17
Infections and infestations     
Upper respiratory tract infection  70/186 (37.63%)  123 67/187 (35.83%)  127
Influenza  16/186 (8.60%)  22 13/187 (6.95%)  17
Herpes simplex  3/186 (1.61%)  7 12/187 (6.42%)  15
Nasopharyngitis  6/186 (3.23%)  8 10/187 (5.35%)  10
Injury, poisoning and procedural complications     
Gastroenteritis  19/186 (10.22%)  24 17/187 (9.09%)  25
Musculoskeletal and connective tissue disorders     
Back pain  23/186 (12.37%)  31 12/187 (6.42%)  14
Arthralgia  16/186 (8.60%)  21 11/187 (5.88%)  14
Pain in extremity  11/186 (5.91%)  11 13/187 (6.95%)  16
Nervous system disorders     
Headache  24/186 (12.90%)  27 28/187 (14.97%)  33
Dizziness  14/186 (7.53%)  17 7/187 (3.74%)  9
Psychiatric disorders     
Depression  17/186 (9.14%)  21 24/187 (12.83%)  30
Insomnia  10/186 (5.38%)  10 12/187 (6.42%)  14
Anxiety  7/186 (3.76%)  8 15/187 (8.02%)  16
Respiratory, thoracic and mediastinal disorders     
Cough  16/186 (8.60%)  18 10/187 (5.35%)  11
Pharyngolaryngeal pain  7/186 (3.76%)  7 10/187 (5.35%)  10
Vascular disorders     
Hypertension  12/186 (6.45%)  19 9/187 (4.81%)  10
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.
All presentations and publications of data from CDC funded studies are subject to CDC clearance prior to publication or presentation.
Results Point of Contact
Name/Title: Taraz Samandari
Organization: Centers for Disease Control and Prevention (CDC)
Phone: 404-639-1676
EMail: tts0@cdc.gov
Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT00131677     History of Changes
Other Study ID Numbers: CDC-NCHHSTP-4323
First Submitted: August 17, 2005
First Posted: August 19, 2005
Results First Submitted: August 8, 2013
Results First Posted: March 10, 2014
Last Update Posted: March 10, 2014