Comparative Safety Study of Two Vaginal Applicators With Tenofovir

Comparative Safety Study of Pre-Filled Plastic and User-Filled Paper Vaginal Applicators With Candidate Microbicide, Tenofovir

The primary objective of this study is to compare the effect of two vaginal applicators, delivering the candidate microbicide Tenofovir, on symptoms and signs of irritation of the external genitalia, cervix and vagina as seen on colposcopy after seven days of twice daily use.

The secondary objectives are to:

1. Evaluate and compare the dosing accuracy and precision of the user-filled applicator and pre-filled applicator with the candidate microbicide, Tenofovir.
2. Compare the acceptability of the user-filled applicator with the pre-filled applicator.

Inclusion Criteria:

• Female
• Age 18 to 50, inclusive
• Pre-menopausal
• In good health as reported by individual
• Have regular menstrual cycles (24 to 35 days)
• Low risk for sexually transmitted infections (only one sexual partner in the last three months)
• Not pregnant or at risk of pregnancy (must either have had a tubal ligation, or currently be using a hormonal method of contraception)
• Negative on a urine pregnancy test
• Willing to abstain from sexual intercourse and masturbation during two 7-day periods when applicators are being used
• Willing to abstain from use of vaginal products during course of study (including douching, use of vaginal applicators for medication, lubrication, sex toys, other)
• Willing to follow procedural requirements of study
• Willing and able to provide informed consent for study participation
• Willing to provide investigator with phone number or address where she can be reached during the study

Exclusion Criteria:

• History of hysterectomy
• Pregnancy or within two months of last pregnancy outcome (delivery, spontaneous or induced abortion, medical or surgical management of ectopic pregnancy)
• Post-menopausal
• Breastfeeding
• Use of an intra-uterine device (IUD), cervical caps or diaphragm for contraceptive purposes
• Diagnosis or treatment for a sexually transmitted disease within the past 30 days;
• More than one sexual partner in the last 3 months
• Has had surgery on the external genitalia, vagina, or cervix within the past 3 months;
• Current or past use of any anti-retroviral therapies including but not limited to systemic Tenofovir (Viread®)
• 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 time of screening
• Hepatitis B surface antigen (HBsAg) positive at time of screening
• Positive test results for Neisseria gonorrhea, Chlamydia trachomatis, or Trichomonas vaginalis at time of screening.
• At baseline colposcopic exam (Visit 2), findings involving disruption of epithelium with disruption of blood vessels or deep disruption of epithelium alone. Any area of epithelium with bleeding will be considered deeply disrupted.
• Any abnormal finding on colposcopic exams which in the opinion of the investigator, precludes participation in the study
• At baseline exams, clinical symptoms or signs of vaginitis or vulvitis confirmed by a wet mount exam of the discharge. Note: If vaginitis or vulvitis is present at either baseline exam (visits 2 or 10), volunteer will be treated and rescheduled for new baseline exam one week after application of last treatment dose. If signs or symptoms are still present at the rescheduled baseline exam for Visit 2, the volunteer will not be enrolled into study. If signs or symptoms are still present at the rescheduled baseline exam for Visit 10, the volunteer will be discontinued from the study.
• Serum chemistry (glucose, creatinine, bilirubin, AST [aspartate aminotransferase] and ALT [alanine transaminase]) not within normal expected levels according to the specifications of the local laboratory.
• Hemoglobin, hematocrit and total white blood cell not within 15 % of lower and upper limit normal levels according to the specifications of the local laboratory.
• Participation in any other research study in the 30 days prior to screening and/or plans to participate in any other research study during the entire study duration.