Comparative Safety Study of Two Vaginal Applicators With Tenofovir

Study Overview
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Brief Summary
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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: Evaluate and compare the dosing accuracy and precision of the user-filled applicator and pre-filled applicator with the candidate microbicide, Tenofovir. Compare the acceptability of the user-filled applicator with the pre-filled applicator.

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

Conditions
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Microbicide Applicator

Intervention / Treatment
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* Drug: Tenofovir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: User-Filled Applicator<br> | Drug: Tenofovir<br>* Delivered using prefilled and user-filled applicator<br>* Other names: TFV;|
| Other: Prefilled applicator<br> | Drug: Tenofovir<br>* Delivered using prefilled and user-filled applicator<br>* Other names: TFV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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) | 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) | 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. | 3 dose delivery measurements during 1 week of product use | 
| 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. | 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) | 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) | 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. | 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. | Final study visit (after completing both study arms) | 
| Number of Respondents Reporting Confidence With Filling the User-filled Applicator | Participants were asked when using the user-filled applicator, how confident did they feel that they at inserted the correct amount of gel into the applicator. Response categories included very confident, confident, and not confident. (Note: this question does not apply to the prefilled applicator.) | Final study visit (after completing both study arms) | 
| Reasons Given by Participants for Knowing When the Applicator Was Filled Correctly | Participants were asked how did they know when the applicator was filled correctly (that is, with the right amount of gel). More than one answer was allowed. Response categories included plunger automatically stopped, the 'FULL' line was reached, and other. Note: this question does not apply to the prefilled applicator. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting Applicator Easy to Insert | Participants were asked to describe the insertion of the applicator into the vagina for each applicator (user-filled and prefilled). Response categories included easy, moderately difficult, and difficult. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting That the Gel Was Easy to Dispense | Participants were asked to describe the dispensing of the gel into the vagina with each applicator (user-filled and prefilled). Response categories included easy, moderately difficult, and difficult. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting Applicator Preference (User-filled or Prefilled) Across a Variety of Factors | Participants were asked about their preference for either the user-filled or prefilled applicator with regard to several use factors as well as in relation to disposal, storage, and overall comfort and preference. Response categories included user-filled, prefilled, and same. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting That Applicator Was Comfortable to Use | Participants were asked to describe the comfort of use for each applicator type(user-filled and prefilled). Response categories included comfortable, neutral, and uncomfortable. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting Suggestions Regarding Ease of Use or Comfort | Participants were asked if they could suggest ways that would make each applicator easier or more comfortable to use. Response categories were yes and no. If yes, participants were asked to describe how they would make the applicator easier and/or more comfortable to use. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting That the Instructions for Use Were Helpful | For each applicator type, participants were asked if the instructions were helpful to you. Response categories were yes and no. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting That Both Applicators Were Acceptable | Participants were asked if both applicators were acceptable to them. Responses were either yes or no. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting That the Cost of the Applicator Would Influence Their Choice of Applicator | Participants were asked if the cost of the applicator would influence their choice of applicator. Response categories were yes, no, and maybe. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting That They Would Use the User-filled Applicator in the Future if it Came With a Gel for HIV Prevention | Participants were asked if they would use the user-filled applicator in the future if it came with a gel that helped prevent HIV infection. Response categories included yes, no, and in some circumstances. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting That They Would Not Want to Use the User-filled Applicator in the Future if it Came With a Gel for HIV Prevention | Participants were asked if there were any reasons that they would not want to use this user-filled applicator in the future if it came with a gel that helped prevent HIV infection. Response categories included yes, no, and in some circumstances. | Final study visit (after completing both study arms) | 
| Number of Participants Reporting That They Would Recommend the User-filled Applicator for HIV Prevention | Participants were asked if they would recommend the user-filled applicator to other women if it came with a gel that helped prevent HIV infection. Response categories included yes, no, and in some circumstances. | Final study visit (after completing both study arms) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbicide, Applicator, Safety