Pharmacokinetic Study of the Vaginal Microbicide Agent 1% Tenofovir Gel

This study has been completed.
Sponsor:
Collaborators:
International Partnership for Microbicides, Inc.
Gilead Sciences
Information provided by:
CONRAD
ClinicalTrials.gov Identifier:
NCT00561496
First received: November 19, 2007
Last updated: May 27, 2008
Last verified: May 2008
  Purpose

This is a multi-center, pharmacokinetic study involving a single-dose phase, a wash out phase and a two-week once or twice-daily dosing phase for each of 49 volunteers.

In the single-dose phase, each volunteer will apply the single dose in the clinic. Participants will be randomized to have cervicovaginal samples and biopsies collected at one of seven time-points [0.5, 1, 2, 4, 6, 8, and 24 hour(s)] after the single-dose. Blood samples will be drawn at 0.5, 1, 2, 4, 6, 8, and 24 hour(s) after the single-dose.

In the two-week phase, the study supplies will be distributed and the participants will be randomized to apply each dose either once or twice-daily for two weeks. At the one week follow-up visit a blood sample will be drawn prior to the morning dose to obtain a trough value and cervicovaginal samples will be collected four hours after the morning dose. At the two week follow-up visit blood samples will be drawn prior to the morning dose to obtain a trough value and then at 0.5, 1, 2, 4, 6, 8, and 24 hour(s) from the final morning dose. Participants will be randomized to have cervicovaginal samples and biopsies collected at either 4, 8 or 24 hours after the final morning dose.

Up to 10 participants who have completed the first two phases of the study, will be asked to participate in a third phase to have cervicovaginal samples, biopsies and blood samples collected 12 hours after a single-dose.


Condition Intervention Phase
HIV Infections
Drug: Tenofovir gel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Single Dose and 14-Day Once or Twice-Daily Pharmacokinetic Study of the Vaginal Microbicide Agent 1% Tenofovir Gel

Resource links provided by NLM:


Further study details as provided by CONRAD:

Primary Outcome Measures:
  • Concentration of tenofovir in local genital tract compartments (intraluminal, mononuclear cells and vaginal tissue levels). Concentration (Cmax) and time of maximum concentration (Tmax) of tenofovir in the systemic compartment. [ Time Frame: Single dose; two weeks (after once or twice-daily vaginal administration) ]

Enrollment: 49
Study Start Date: March 2007
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Twice daily
Tenofovir gel intravaginal twice daily for 14 days
Drug: Tenofovir gel
Intravaginal (4grams)single dose followed by fourteen days
Other Name: 9-[(R)-2-(phosphonomethoxy)propyl] adenine or PMPA
Once daily
Tenofovir gel intravaginal once daily for 14 days
Drug: Tenofovir gel
Intravaginal (4grams)single dose followed by fourteen days
Other Name: 9-[(R)-2-(phosphonomethoxy)propyl] adenine or PMPA

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Must be between 18-45 years old, inclusive
  • Must be in general good health by volunteer history without any clinically significant systemic disease (including liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, osteoporosis or bone disease)
  • Must have regular menstrual cycles (minimum of 26 and maximum of 38 days)
  • Must be at least 2 months since last pregnancy outcome and have had at least two spontaneous menses
  • Must abstain from sexual activity and use of intravaginal products for 72 hours prior to the start of the single-dose phase and multi-dose phase, for at least one week following vaginal biopsies and for the duration of the study phases
  • Willingness to give voluntary consent, sign an informed consent form and comply with study procedures as required by the protocol

Exclusion Criteria:

  • Currently pregnant or at risk for pregnancy (may be using Paragard® IUD, effective barrier method, female sterilization or abstinence, or be sexually active with a vasectomized partner)
  • Currently breastfeeding or planning to breastfeed during the course of the study
  • Use of any hormonal contraceptives within 30 days of enrollment
  • Use of Depo-Provera within 120 days of enrollment History of abnormal Pap smear (by volunteer history) that has not been evaluated and treated, if indicated, according to standard guidelines
  • Current vaginal or urinary tract infection
  • Positive test for Neisseria gonorrhea or Chlamydia trachomatis at the time of screening
  • Positive wet mount for Trichomonas vaginalis at the time of screening or enrollment
  • Deep epithelial genital findings such as abrasions, ulcerations, and lacerations, or vesicles suspicious for a sexually transmitted infection
  • Current or past use of any anti-retroviral therapies including but not limited to systemic tenofovir (Viread®)
  • Current or recent drug or alcohol abuse
  • Current or anticipated use of drugs on a daily basis that may reduce renal function (e.g. acyclovir or ibuprofen) or liver function (e.g. tylenol)
  • HIV positive at the time of screening
  • Hepatitis B surface antigen (HBsAg) positive at the time of screening
  • Grade 1 or higher serum chemistry or complete blood count abnormality in accordance with DAIDS toxicity table values
  • Abnormal finding on laboratory or physical examination or a medical condition which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data
  • Participation in any other research study in the 30 days prior to screening and/or plans to participate in any other research study during entire study duration
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00561496

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Advances in Health, Inc
Houston, Texas, United States, 77030
Dominican Republic
Profamilia
Santo Domingo, Dominican Republic
Sponsors and Collaborators
CONRAD
International Partnership for Microbicides, Inc.
Gilead Sciences
Investigators
Study Director: Jill Schwartz, MD CONRAD
  More Information

No publications provided by CONRAD

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jill Schwartz, MD/Project Leader, CONRAD
ClinicalTrials.gov Identifier: NCT00561496     History of Changes
Other Study ID Numbers: A04-095
Study First Received: November 19, 2007
Last Updated: May 27, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by CONRAD:
HIV prevention
Microbicides
Pharmacokinetics
vaginal biopsies

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Tenofovir disoproxil
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 21, 2014