Comparative Safety Study of Two Vaginal Applicators With Tenofovir

This study has been completed.
Sponsor:
Collaborators:
CONRAD
Profamilia, Santo Domingo, DR
Information provided by (Responsible Party):
PATH
ClinicalTrials.gov Identifier:
NCT01283555
First received: January 24, 2011
Last updated: July 10, 2012
Last verified: June 2012
  Purpose

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.

Condition Intervention
Microbicide Applicator
Drug: Tenofovir

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Comparative Safety Study of Pre-Filled Plastic and User-Filled Paper Vaginal Applicators With Candidate Microbicide, Tenofovir

Resource links provided by NLM:


Further study details as provided by PATH:

Primary Outcome Measures:
  • Number of Colposcopic Findings (Baseline and After One Week of Product Use) [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Filled Volume [ Time Frame: 3 dose delivery measurements during 1 week of product use ] [ Designated as safety issue: No ]
    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.

  • Filling Precision (5% Range) [ Time Frame: 3 dose delivery measurements during 1 week of product use ] [ Designated as safety issue: No ]
    A 5% range was calculated around the average filled volumes to determine how many applicators were filled within this range (+/-5% of average volume)

  • Filling Precision (10% Range) [ Time Frame: 3 dose delivery measurements during 1 week of product use ] [ Designated as safety issue: No ]
    A 10% range was calculated around the average filled volumes to determine how many applicators were filled within this range (+/-10% of average volume)

  • Filling Accuracy (% of Target Dose) [ Time Frame: 3 dose delivery measurements during 1 week of product use ] [ Designated as safety issue: No ]
    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.

  • Dosing Volume (Expressed Volume) [ Time Frame: 3 dose delivery measurements during 1 week of product use ] [ Designated as safety issue: No ]
    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.

  • Dosing Precision, 5% (Expressed Volume) [ Time Frame: 3 dose delivery measurements during 1 week of product use ] [ Designated as safety issue: No ]
    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)

  • Dosing Precision, 10% (Expressed Volume) [ Time Frame: 3 dose delivery measurements during 1 week of product use ] [ Designated as safety issue: No ]
    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)

  • Dosing Accuracy (% of Target Dose Delivered) [ Time Frame: 3 dose delivery measurements during 1 week of product use ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Reporting Applicator Easy to Fill [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    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.


  • Number of Respondents Reporting Confidence With Filling the User-filled Applicator [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    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.)


  • Reasons Given by Participants for Knowing When the Applicator Was Filled Correctly [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    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.


  • Number of Participants Reporting Applicator Easy to Insert [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    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".


  • Number of Participants Reporting That the Gel Was Easy to Dispense [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    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".


  • Number of Participants Reporting Applicator Preference (User-filled or Prefilled) Across a Variety of Factors [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    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".


  • Number of Participants Reporting That Applicator Was Comfortable to Use [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    Participants were asked to describe the comfort of use for each applicator type(user-filled and prefilled).

    Response categories included "comfortable", "neutral", and "uncomfortable".


  • Number of Participants Reporting Suggestions Regarding Ease of Use or Comfort [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Reporting That the Instructions for Use Were Helpful [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    For each applicator type, participants were asked if the instructions were helpful to you.

    Response categories were "yes" and "no".


  • Number of Participants Reporting That Both Applicators Were Acceptable [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]
    Participants were asked if both applicators were acceptable to them. Responses were either "yes" or "no".

  • Number of Participants Reporting That the Cost of the Applicator Would Influence Their Choice of Applicator [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    Participants were asked if the cost of the applicator would influence their choice of applicator.

    Response categories were "yes", "no", and "maybe".


  • Number of Participants Reporting That They Would Use the User-filled Applicator in the Future if it Came With a Gel for HIV Prevention [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    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".


  • 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 [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    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".


  • Number of Participants Reporting That They Would Recommend the User-filled Applicator for HIV Prevention [ Time Frame: Final study visit (after completing both study arms) ] [ Designated as safety issue: No ]

    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".



Enrollment: 25
Study Start Date: January 2011
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: User-Filled Applicator Drug: Tenofovir
Delivered using prefilled and user-filled applicator
Other Name: TFV
Prefilled applicator Drug: Tenofovir
Delivered using prefilled and user-filled applicator
Other Name: TFV

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01283555

Locations
Dominican Republic
Clinica Profamilia
Santo Domingo, Dominican Republic, 10401
Sponsors and Collaborators
PATH
CONRAD
Profamilia, Santo Domingo, DR
Investigators
Principal Investigator: Vivian Brache Profamilia
  More Information

No publications provided

Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT01283555     History of Changes
Other Study ID Numbers: PATH HS-522
Study First Received: January 24, 2011
Results First Received: February 16, 2012
Last Updated: July 10, 2012
Health Authority: United States: Food and Drug Administration
Dominican Republic: Consejo Nacional de Bioetica en Salud

Keywords provided by PATH:
Microbicide, Applicator, Safety

Additional relevant MeSH terms:
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014