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

NCT00131677 | Completed Phase 2 Results DMC

• 1 other identifier: CDC-NCHHSTP-4323
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (2)

• 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)

• 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)

Secondary Outcomes (3)

• Number of Breakthrough HIV Infections

  24 months (immediate arm) and 15 months (delayed arm)

• Adherence to Study Drug

  24 months (immediate arm) and 15 months (delayed arm)

• Behavioral Safety--Unprotected Anal Sex (UAS)

  Nine months

Other Outcomes (1)

• >5% Bone Mineral Density Decline at Femoral Neck

  24 months (immediate arm), 15 months (delayed arm)

Study Arms (4)

active immediate

ACTIVE COMPARATOR

participants in this arm start study product immediately upon enrollment

Drug: tenofovir disoproxil fumarate

placebo immediate

PLACEBO COMPARATOR

participants in this arm start study product immediately upon enrollment

Drug: placebo

active delayed

ACTIVE COMPARATOR

persons in this arm start study product 9 months after enrollment

Drug: tenofovir disoproxil fumarate

placebo delayed

PLACEBO COMPARATOR

participants in this arm start study product nine months after enrollment

Drug: placebo

Interventions

tenofovir disoproxil fumarate DRUG

study product taken daily

Also known as: Viread

active delayed; active immediate

placebo DRUG

study product taken daily

placebo delayed; placebo immediate

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy biologic male (male at birth)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• San Francisco Department of Public Health: collaborator
• AIDS Research Consortium of Atlanta: collaborator

Study Sites (3)

San Francisco Department of Public Health

San Francisco, California, 94102, United States

Location

AIDS Research Consortium of Atlanta

Atlanta, Georgia, 30308, United States

Location

Fenway Community Health

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• 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.

  PMID: 29315307 DERIVED

• 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.

  PMID: 21897852 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Taraz Samandari
• Organization: Centers for Disease Control and Prevention (CDC)

tts0@cdc.gov

404-639-1676

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2005
• First Posted: August 19, 2005
• Study Start: February 1, 2005
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: March 10, 2014
• Results First Posted: March 10, 2014

Record last verified: 2013-08

Locations

US (3)