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

• 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: Centers for Disease Control and Prevention
• Collaborators: San Francisco Department of Public Health; AIDS Research Consortium of Atlanta
• Information provided by (Responsible Party): Centers for Disease Control and Prevention

Tracking Information

• First Submitted Date: August 17, 2005
• First Posted Date: August 19, 2005
• Results First Submitted Date: August 8, 2013
• Results First Posted Date: March 10, 2014
• Last Update Posted Date: March 10, 2014
• Study Start Date: February 2005
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 22, 2014)

• Clinical Safety--Creatinine Elevations [ Time Frame: 24 months (immediate arm) and 15 months (delayed arm) ]
  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) ]
  Grade 3 or 4 hypophosphatemia (per National Institutes of Health Division of AIDS toxicity scale)

• Original Primary Outcome Measures (submitted: August 17, 2005): Clinical and behavioral safety

Current Secondary Outcome Measures (submitted: January 22, 2014)

• Number of Breakthrough HIV Infections [ Time Frame: 24 months (immediate arm) and 15 months (delayed arm) ]
  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) ]
  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 ]
  Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study.

Original Secondary Outcome Measures (submitted: August 17, 2005)

• Number of HIV infections
• Genetic characteristics of HIV-1 breakthrough viruses
• Participants' adherence with daily TDF

Current Other Pre-specified Outcome Measures (submitted: January 22, 2014)

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

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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Extended Safety Study of Tenofovir Disoproxil Fumarate (TDF) Among HIV-1 Negative Men
• Official Title: Phase II Extended Safety Study of Tenofovir Disoproxil Fumarate (TDF) Among HIV-1 Negative Men
• Brief Summary: The purpose of this study is to examine safety and tolerability of daily tenofovir use in HIV-uninfected men.
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: HIV Infection

Intervention

• Drug: tenofovir disoproxil fumarate
  study product taken daily
  Other Name: Viread
• Drug: placebo
  study product taken daily

Study Arms

• Active Comparator: active immediate
  participants in this arm start study product immediately upon enrollment
  Intervention: Drug: tenofovir disoproxil fumarate
• Placebo Comparator: placebo immediate
  participants in this arm start study product immediately upon enrollment
  Intervention: Drug: placebo
• Active Comparator: active delayed
  persons in this arm start study product 9 months after enrollment
  Intervention: Drug: tenofovir disoproxil fumarate
• Placebo Comparator: placebo delayed
  participants in this arm start study product nine months after enrollment
  Intervention: Drug: placebo

Publications *

• Baxi SM, Vittinghoff E, Bacchetti P, Huang Y, Chillag K, Wiegand R, Anderson PL, Grant R, Greenblatt RM, Buchbinder S, Gandhi M, Liu AY. Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial. PLoS One. 2018 Jan 9;13(1):e0190118. doi: 10.1371/journal.pone.0190118. eCollection 2018.
• Liu AY, Vittinghoff E, Sellmeyer DE, Irvin R, Mulligan K, Mayer K, Thompson M, Grant R, Pathak S, O'Hara B, Gvetadze R, Chillag K, Grohskopf L, Buchbinder SP. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS One. 2011;6(8):e23688. doi: 10.1371/journal.pone.0023688. Epub 2011 Aug 29.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 17, 2005): 400
• Original Enrollment: Same as current
• Actual Study Completion Date: August 2009
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00131677
• Other Study ID Numbers: CDC-NCHHSTP-4323
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Centers for Disease Control and Prevention
• Study Sponsor: Centers for Disease Control and Prevention

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

• PRS Account: Centers for Disease Control and Prevention
• Verification Date: August 2013