Comparative Safety Study of Two Vaginal Applicators With Tenofovir

PATH25 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Microbicide Applicator

Interventions

TenofovirDRUG

Delivered using prefilled and user-filled applicator

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Clinica Profamilia

Santo Domingo, Dominican Republic

Outcomes

Primary Outcomes

Number of Colposcopic Findings (Baseline and After One Week of Product Use)

Comparison of colposcopic findings between baseline visits and after one week of twice-daily application of Tenofovir 1% gel with either a user-filled or prefilled applicator

Time frame: 7 days

Secondary Outcomes

Filled Volume

At each dose delivery visit, the applicator was weighed, prior to vaginal insertion. For the user-filled applicator, the participant handed the applicator to the investigator after filling with gel from the multidose tube. The applicator was then weighed and returned to the participant for insertion. For the prefilled applicator, the participant inserted the plunger into the barrel, and then handed the applicator to the investigator for weighing.

Time frame: 3 dose delivery measurements during 1 week of product use

Filling Precision (5% Range)

A 5% range was calculated around the average filled volumes to determine how many applicators were filled within this range (+/-5% of average volume)

Time frame: 3 dose delivery measurements during 1 week of product use

Filling Precision (10% Range)

A 10% range was calculated around the average filled volumes to determine how many applicators were filled within this range (+/-10% of average volume)

Time frame: 3 dose delivery measurements during 1 week of product use

Filling Accuracy (% of Target Dose)

The target dose for Tenofovir gel in this study was 4.0ml, which is the volume of Tenofovir being used in current microbicide clinical trials. The filled volume for each applicator was compared with the intended target dose of 4.0ml.

Time frame: 3 dose delivery measurements during 1 week of product use

Data from ClinicalTrials.gov

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Dosing Volume (Expressed Volume)

At each dose delivery visit, the applicator was weighed prior to vaginal insertion and after use. The volume of gel expressed was measured using the following data: weight of filled applicator, weight of emptied applicator, the average weight of an empty applicator, and gel density.

Time frame: 3 dose delivery measurements during 1 week of product use

Dosing Precision, 5% (Expressed Volume)

A 5% range was calculated around the average expressed volume of 3.83ml to determine how many applicators delivered a dose within this range (+/-5% of average volume)

Time frame: 3 dose delivery measurements during 1 week of product use

Dosing Precision, 10% (Expressed Volume)

A 10% range was calculated around the average expressed volume of 3.83ml to determine how many applicators delivered a dose within this range (+/-10% of average volume)

Time frame: 3 dose delivery measurements during 1 week of product use

Dosing Accuracy (% of Target Dose Delivered)

The target dose for Tenofovir gel in this study was 4.0ml, which is the volume of Tenofovir being used in current microbicide clinical trials. The average dose delivered for each applicator was compared with the intended target dose of 4.0ml.

Time frame: 3 dose delivery measurements during 1 week of product use

Number of Participants Reporting Applicator Easy to Fill

Participants were asked to describe the process of filling the user-filled applicator. Response categories included "easy", "moderately difficult", and "difficult". Since "ease of filling" only applies to the user-filled applicator, this question was not applicable for the prefilled applicator.