Clinical trial NCT00122512: Study of Tenofovir Disoproxil Fumarate (TDF) for Prevention of HIV
Official title: Phase 2a Study of Tenofovir Disoproxil Fumarate (TDF) for Prevention of HIV - An Extended Safety Evaluation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV Infections
Keywords: AE adverse event
AIDS acquired immunodeficiency syndrome
ALT (SGPT) alanine aminotransferase
ART antiretroviral therapy
AST (SGOT) aspartate aminotransferase
DCF data collection forms
DMC Data Monitoring Committee
FDA (U.S.) Food and Drug Administration
GCP Good Clinical Practice guidelines
HB sAg Hepatitis B surface antigen
ICH International Conference of Harmonisation
IND Investigational New Drug Application
IRB Institutional Review Board
IU international units
mg milligram(s)
mm3 cubic millimeter(s)
PCR polymerase chain reaction
SAE serious adverse event
TDF tenofovir disoproxil fumarate, GS-4331-05, PMPA prodrug
µg microgram
ULN upper limit of the normal range
WB Western Blot
Human Immunodeficiency Virus
HIV Seronegativity
Lead sponsor: FHI 360
Sponsor class: OTHER
First posted: 2005-07-22
Enrollment: 500
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This Phase 2a study involving Tenofovir Disoproxil Fumarate (TDF) will provide extended safety data for high-risk men. Secondarily, the study will assess the feasibility of conducting the trial and evaluate the preliminary effectiveness of TDF 300 mg as an HIV prevention method when taken once a day.

Detailed description: TDF has been selected for investigation as prophylaxis against HIV in high-risk men because of its unique pharmacologic profile. In addition to the convenience of being a once daily single tablet, TDF's safety profile is comparable to placebo among HIV infected persons, it has striking anti-HIV potency, and it has low potential for selection of resistant viruses. TDF is cleared from the body by the kidneys and is not metabolized by the liver. Therefore, TDF has limited potential to have pharmacokinetic interactions with other hepatically metabolized drugs. Each of these properties is necessary given the realities of the intended target populations. Moreover, initial prevention studies in simian models have provided encouraging results. Finally, the drug's sponsor is supportive of investigating the potential use of TDF as a preventive, as well as therapeutic agent, will provide TDF for the study, and is willing to make a good faith effort to make TDF available for public health use should it prove to be effective for HIV prevention.

Eligibility criteria: * Be willing and able to give informed consent
* Be 18 years or older
* Be willing to use study product as directed
* Be willing to adhere to follow-up schedule
* Be willing to participate in the study for up to 12 months
* Be in general good health (no active, serious infections that require parenteral antibiotics, no active clinically significant medical conditions, including heart disease, diabetes, asthma, alcoholism, and cancer)
* Meet at least one of these three high risk criteria: \*Sex with sex worker/bar girl in last 3 months;

  * Sex with 2 or more women in last 3 months;
  * Sexually transmitted disease (STD) in last 3 months
* Have absence of HIV antibodies by rapid test (at screening and enrollment visit)
* Have absence of hepatitis B (HB) surface antigen (sAg)
* Have adequate renal function (serum creatinine \<1.5 mg/dL)
* Have adequate liver function (hepatic transaminases (ALT \<54 U/L and AST\<46 U/L)
* Have adequate serum phosphorus (\>2.2 mg/dL)
* Not be intending to relocate out of the area for the duration of the study participation and does not have a job or other obligations that may require long absences from the area
* Not be receiving an experimental HIV vaccine

Primary outcomes:
measure: To evaluate the extended safety of TDM 300mg daily among HIV-uninfected men
Secondary outcomes:
measure: To evaluate the feasibility (i.e. accrual, retention, adherence, change in behavior) of conducting a large scale trial of TDF for HIV prevention in men recruited from a resource-limited setting
measure: To assess the preliminary effectiveness of TDF in preventing HIV infection among men at high risk for HIV
Other outcomes:
Locations:
city: Lilongwe
country: Malawi
facility: UNC Project, Kamuzu Central Hospital
Study officials:
affiliation: UNC Center for Infectious Diseases
name: Irving Hoffman, PA, MPH
role: PRINCIPAL_INVESTIGATOR
References: