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

HIV Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00131677
• Other study ID #: CDC-NCHHSTP-4323
• Status: Completed
• Phase: Phase 2
• First received: August 17, 2005
• Last updated: January 22, 2014
• Start date: February 2005
• Est. completion date: August 2009

Study information

• Verified date: August 2013
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infection

Intervention

Drug:
• tenofovir disoproxil fumarate
study product taken daily
• placebo
study product taken daily

Locations

Country	Name	City	State
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Fenway Community Health	Boston,	Massachusetts
United States	San Francisco Department of Public Health	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	AIDS Research Consortium of Atlanta, San Francisco Department of Public Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	>5% Bone Mineral Density Decline at Femoral Neck	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.	24 months (immediate arm), 15 months (delayed arm)	Yes
Primary	Clinical Safety--Creatinine Elevations	Grade 3 or 4 Creatinine elevations (per National Institutes of Health Division of AIDS toxicity scale)	24 months (immediate arm) and 15 months (delayed arm)	Yes
Primary	Clinical Safety--Hypophosphatemia	Grade 3 or 4 hypophosphatemia (per National Institutes of Health Division of AIDS toxicity scale)	24 months (immediate arm), 15 months (delayed arm)	Yes
Secondary	Number of Breakthrough HIV Infections	Number of participants with HIV seroconversions occuring while on study drug	24 months (immediate arm) and 15 months (delayed arm)	Yes
Secondary	Adherence to Study Drug	Estimated exposure to study drug (active and placebo) as assessed by Medication Event Monitoring System (MEMS) caps.	24 months (immediate arm) and 15 months (delayed arm)	No
Secondary	Behavioral Safety--Unprotected Anal Sex (UAS)	Change in percent of participants reporting unprotected anal intercourse--baseline vs. months 3 through 9 on study.	Nine months	Yes