search
Back to results

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

Primary Purpose

HIV Infection

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
tenofovir disoproxil fumarate
placebo
Sponsored by
Centers for Disease Control and Prevention
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infection

Eligibility Criteria

18 Years - 60 Years (Adult)MaleAccepts Healthy Volunteers

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.

Sites / Locations

  • San Francisco Department of Public Health
  • AIDS Research Consortium of Atlanta
  • Fenway Community Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

active immediate

placebo immediate

active delayed

placebo delayed

Arm Description

participants in this arm start study product immediately upon enrollment

participants in this arm start study product immediately upon enrollment

persons in this arm start study product 9 months after enrollment

participants in this arm start study product nine months after enrollment

Outcomes

Primary Outcome Measures

Clinical Safety--Creatinine Elevations
Grade 3 or 4 Creatinine elevations (per National Institutes of Health Division of AIDS toxicity scale)
Clinical Safety--Hypophosphatemia
Grade 3 or 4 hypophosphatemia (per National Institutes of Health Division of AIDS toxicity scale)

Secondary Outcome Measures

Number of Breakthrough HIV Infections
Number of participants with HIV seroconversions occuring while on study drug
Adherence to Study Drug
Estimated exposure to study drug (active and placebo) as assessed by Medication Event Monitoring System (MEMS) caps.
Behavioral Safety--Unprotected Anal Sex (UAS)
Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study.

Full Information

First Posted
August 17, 2005
Last Updated
January 22, 2014
Sponsor
Centers for Disease Control and Prevention
Collaborators
San Francisco Department of Public Health, AIDS Research Consortium of Atlanta
search

1. Study Identification

Unique Protocol Identification Number
NCT00131677
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
August 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centers for Disease Control and Prevention
Collaborators
San Francisco Department of Public Health, AIDS Research Consortium of Atlanta

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
400 (Actual)

8. Arms, Groups, and Interventions

Arm Title
active immediate
Arm Type
Active Comparator
Arm Description
participants in this arm start study product immediately upon enrollment
Arm Title
placebo immediate
Arm Type
Placebo Comparator
Arm Description
participants in this arm start study product immediately upon enrollment
Arm Title
active delayed
Arm Type
Active Comparator
Arm Description
persons in this arm start study product 9 months after enrollment
Arm Title
placebo delayed
Arm Type
Placebo Comparator
Arm Description
participants in this arm start study product nine months after enrollment
Intervention Type
Drug
Intervention Name(s)
tenofovir disoproxil fumarate
Other Intervention Name(s)
Viread
Intervention Description
study product taken daily
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
study product taken daily
Primary Outcome Measure Information:
Title
Clinical Safety--Creatinine Elevations
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)
Title
Clinical Safety--Hypophosphatemia
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)
Secondary Outcome Measure Information:
Title
Number of Breakthrough HIV Infections
Description
Number of participants with HIV seroconversions occuring while on study drug
Time Frame
24 months (immediate arm) and 15 months (delayed arm)
Title
Adherence to Study Drug
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)
Title
Behavioral Safety--Unprotected Anal Sex (UAS)
Description
Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study.
Time Frame
Nine months
Other Pre-specified Outcome Measures:
Title
>5% Bone Mineral Density Decline at Femoral Neck
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)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kata L Chillag, PhD
Organizational Affiliation
Centers for Disease Control and Prevention
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lisa A Grohskopf, MD, MPH
Organizational Affiliation
Centers for Disease Control and Prevention
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Susan Buchbinder, MD
Organizational Affiliation
San Francisco Dept. of Public Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Melanie Thompson, MD
Organizational Affiliation
AIDS Research Consortium of Atlanta
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kenneth H. Mayer, MD
Organizational Affiliation
Fenway Community Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
San Francisco Department of Public Health
City
San Francisco
State/Province
California
ZIP/Postal Code
94102
Country
United States
Facility Name
AIDS Research Consortium of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Fenway Community Health
City
Boston,
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29315307
Citation
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.
Results Reference
derived
PubMed Identifier
21897852
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs