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
  Purpose

The purpose of this study is to examine safety and tolerability of daily tenofovir use in HIV-uninfected men.


Condition Intervention Phase
HIV Infection
Drug: tenofovir disoproxil fumarate
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Phase II Extended Safety Study of Tenofovir Disoproxil Fumarate (TDF) Among HIV-1 Negative Men

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Clinical Safety--Creatinine Elevations [ Time Frame: 24 months (immediate arm) and 15 months (delayed arm) ] [ Designated as safety issue: Yes ]
    Grade 3 or 4 Creatinine elevations (per National Institutes of Health Division of AIDS toxicity scale)

  • Clinical Safety--Hypophosphatemia [ Time Frame: 24 months (immediate arm), 15 months (delayed arm) ] [ Designated as safety issue: Yes ]
    Grade 3 or 4 hypophosphatemia (per National Institutes of Health Division of AIDS toxicity scale)


Secondary Outcome Measures:
  • Number of Breakthrough HIV Infections [ Time Frame: 24 months (immediate arm) and 15 months (delayed arm) ] [ Designated as safety issue: Yes ]
    Number of participants with HIV seroconversions occuring while on study drug

  • Adherence to Study Drug [ Time Frame: 24 months (immediate arm) and 15 months (delayed arm) ] [ Designated as safety issue: No ]
    Estimated exposure to study drug (active and placebo) as assessed by Medication Event Monitoring System (MEMS) caps.

  • Behavioral Safety--Unprotected Anal Sex (UAS) [ Time Frame: Nine months ] [ Designated as safety issue: Yes ]
    Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study.


Other Outcome Measures:
  • >5% Bone Mineral Density Decline at Femoral Neck [ Time Frame: 24 months (immediate arm), 15 months (delayed arm) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 400
Study Start Date: February 2005
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: active immediate
participants in this arm start study product immediately upon enrollment
Drug: tenofovir disoproxil fumarate
study product taken daily
Other Name: Viread
Placebo Comparator: placebo immediate
participants in this arm start study product immediately upon enrollment
Drug: placebo
study product taken daily
Active Comparator: active delayed
persons in this arm start study product 9 months after enrollment
Drug: tenofovir disoproxil fumarate
study product taken daily
Other Name: Viread
Placebo Comparator: placebo delayed
participants in this arm start study product nine months after enrollment
Drug: placebo
study product taken daily

Detailed Description:

This study will assess the clinical and behavioral safety and tolerability of oral daily TDF use as pre-exposure prophylaxis (PrEP) to prevent HIV infection in uninfected men.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy biologic male (male at birth)
  • 18-60 years of age
  • HIV-1 negative by licensed, commercially available, FDA-approved whole blood rapid enzyme immunoassay (EIA) at screening and enrollment
  • Reports any anal sex with a man in the last 12 months
  • Able to understand and pass comprehension assessment questionnaire
  • Able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
  • Able to understand English
  • Adequate renal function: calculated creatinine clearance of at least 70 mL/min
  • Hepatic transaminases (AST and ALT) less than or equal to 2x upper limit of normal (ULN)
  • Total bilirubin less than or equal to 1.5 mg/dL
  • Absolute neutrophil count at least 1,500/mm3;
  • Platelets at least 100,000/mm3;
  • Hemoglobin at least 9.5 g/dL
  • Serum amylase less than or equal to 1.5 x ULN
  • Biochemical profile: within normal limits for serum phosphorus, potassium, sodium, and calcium.
  • Hepatitis B surface antigen negative
  • Normal urine dipstick or urinalysis (UA)

Exclusion Criteria:

  • Active untreated syphilis
  • Current uncontrolled hypertension (blood pressure > 160/100 mmHg)
  • Mutually monogamous for > one year with a known HIV antibody negative partner
  • History of chronic renal disease, known osteoporosis, osteomalacia, or osteopenia
  • Current or expected participation in other longitudinal HIV behavioral or biomedical research study
  • Current HIV antiretroviral use
  • Receiving or planning to receive on-going therapy with any nephrotoxic agents or experimental/investigational agents
  • Previous or expected requirements for the administration of immunosuppressive/ immunomodulatory therapy (e.g. chronic systemic steroids, interferon, interleukins, chemotherapy, radiation).
  • Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication.
  • Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.
  • Imminently life-threatening medical conditions (malignancy, immunosuppressive disease [e.g. lymphoma]), or other serious disease or conditions (e.g. cardiovascular, renal, diabetes) within the last 5 years or that are unstable and/or require chronic medication that would impede compliance with study requirements and complicate the interpretation of adverse events
  • Expected to be non-compliant with study visits or planning to move within 24 months to an area where the study will not be conducted
  • Any other clinical or social condition, prior therapy, occupation, or other responsibility, that, in the opinion of the investigator, would interfere with, or serve as a contraindication to study participation or compliance with the dosing requirements.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131677

Locations
United States, California
San Francisco Department of Public Health
San Francisco, California, United States, 94102
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
United States, Massachusetts
Fenway Community Health
Boston,, Massachusetts, United States, 02115
Sponsors and Collaborators
San Francisco Department of Public Health
AIDS Research Consortium of Atlanta
Investigators
Principal Investigator: Kata L Chillag, PhD Centers for Disease Control and Prevention
Principal Investigator: Lisa A Grohskopf, MD, MPH Centers for Disease Control and Prevention
Principal Investigator: Susan Buchbinder, MD San Francisco Dept. of Public Health
Principal Investigator: Melanie Thompson, MD AIDS Research Consortium of Atlanta
Principal Investigator: Kenneth H. Mayer, MD Fenway Community Health
  More Information

No publications provided by Centers for Disease Control and Prevention

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 22, 2014