Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Exploratory Pharmacodynamic Study of Tenofovir-Based Products

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02722343
Recruitment Status : Completed
First Posted : March 30, 2016
Last Update Posted : September 2, 2016
Sponsor:
Collaborators:
Eastern Virginia Medical School
University of North Carolina
Agility Clinical, Inc.
Information provided by (Responsible Party):
CONRAD

Tracking Information
First Submitted Date  ICMJE March 9, 2016
First Posted Date  ICMJE March 30, 2016
Last Update Posted Date September 2, 2016
Study Start Date  ICMJE April 2016
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2016)
  • p24 antigen production in cervico-vaginal tissues infected with HIV [ Time Frame: Day 14 ]
    • Assess p24 antigen production in cervicovaginal tissues infected ex vivo with HIV-1BaL at baseline and after using Truvada tablets or tenofovir intravaginal ring
  • Analysis of integrated DNA [ Time Frame: Day 14 ]
    Integrated viral DNA in cervicovaginal tissues infected ex vivo with HIV-1BaL at baseline and after using Truvada tablets or tenofovir intravaginal ring
  • Anti-HIV activity in cervicovaginal fluid (CVF) [ Time Frame: Day 14 ]
    Anti-HIV activity in cervicovaginal fluid at baseline and after using Truvada tablets and tenofovir intravaginal ring
Original Primary Outcome Measures  ICMJE
 (submitted: March 23, 2016)
  • p24 antigen production in cervico-vaginal tissues infected with HIV [ Time Frame: Day 0 to day 21 ]
    • Assess p24 antigen production in cervicovaginal tissues infected ex vivo with HIV-1BaL at baseline and after using Truvada tablets or tenofovir intravaginal ring
  • Analysis of integrated DNA [ Time Frame: Day 21 ]
    Analyze integrated viral DNA in cervicovaginal tissues infected ex vivo with HIV-1BaL at baseline and after using Truvada tablets or tenofovir intravaginal ring
  • Measure change in anti-HIV activity in cervicovaginal fluid (CVF) [ Time Frame: Day 1 and 26 ]
    Measure anti-HIV activity in cervicovaginal fluid at baseline and after using Truvada tablets and tenofovir intravaginal ring
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2016)
  • Cervicovaginal tissue, fluid and plasma concentrations of tenofovir [ Time Frame: Day 14 ]
    Concentrations after use of Truvada tablets and tenofovir intravaginal ring
  • Cervicovaginal tissue concentration of tenofovir diphosphate [ Time Frame: Day 14 ]
    Concentrations after use of Truvada tablets and tenofovir intravaginal ring.
  • Cervicovaginal tissue, fluid and plasma concentrations of emtricitabine [ Time Frame: Day 14 ]
    Concentrations after use of Truvada tablets and tenofovir intravaginal ring.
  • Cervicovaginal tissue concentration of emtricitabine triphosphate [ Time Frame: Day 14 ]
    Concentrations after use of Truvada tablets and tenofovir intravaginal ring.
  • Endogenous nucleotide concentrations in cervicovaginal tissue [ Time Frame: Day 14 ]
    Endogenous nucleotides; dATP and dCTP concentrations in cervicovaginal tissue after use of Truvada tablets and tenofovir intravaginal ring
Original Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2016)
  • Determine cervicovaginal tissue, fluid and plasma concentrations of tenofovir [ Time Frame: Day 26 ]
    Determine concentrations after use of Truvada tablets and tenofovir intravaginal ring
  • Determine cervicovaginal tissue concentration of tenofovir diphosphate [ Time Frame: Day 26 ]
    Determine concentrations after use of Truvada tablets and tenofovir intravaginal ring.
  • Determine cervicovaginal tissue, fluid and plasma concentrations of emtricitabine [ Time Frame: Day 26 ]
    Determine concentrations after use of Truvada tablets and tenofovir intravaginal ring.
  • Determine cervicovaginal tissue concentration of emtricitabine triphosphate [ Time Frame: Day 26 ]
    Determine concentrations after use of Truvada tablets and tenofovir intravaginal ring.
  • Determine endogenous nucleotide concentrations in cervicovaginal tissue [ Time Frame: Day 26 ]
    Determine endogenous nucleotides; dATP and dCTP concentrations in cervicovaginal tissue after use of Truvada tablets and tenofovir intravaginal ring
Current Other Pre-specified Outcome Measures
 (submitted: May 16, 2016)
Adherence markers in used IVRs [ Time Frame: Day 14 ]
Adherence biomarkers from used IVRs returned to clinic after two weeks of use
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exploratory Pharmacodynamic Study of Tenofovir-Based Products
Official Title  ICMJE Phase I Exploratory Pharmacodynamic Study of Tenofovir-Based Products
Brief Summary This single site study is designed to describe and measure the efficacy of oral versus vaginal dosing of TFV-based products, specifically emtricitabine/tenofovir disoproxil fumarate oral tablets (Truvada) vs tenofovir intravaginal rings (IVR).
Detailed Description

This study will compare an investigational intravaginal ring containing tenofovir (TFV) with an FDA approved medication in tablet form called Truvada®. It will assess and compare the ability of the tablet and intravaginal ring to prevent HIV transmission (human immunodeficiency virus, the virus that causes AIDS).

The study will enroll healthy, non-pregnant, HIV negative, premenopausal women (aged 18-50, with regular menstrual cycles) who are not at risk of pregnancy.

The enrollment goal is for 20 participants to complete the study.

Participants will be assigned to use one of the study products: oral tablet or intravaginal ring. Participants will take the oral tablet each day for 14 days or wear the intravaginal ring all day and night for 14 days/nights. Blood, genital fluid samples and genital tissue samples (biopsies) will be taken at two visits. These sample collections will take place before and after use of the assigned study product. The samples will be tested to:

  1. Determine the levels of drug in the blood and genital tissue samples
  2. See if the samples taken from the vagina and cervix after use of study product, provides protection from HIV in the laboratory
  3. Ensure that the laboratory test used to measure HIV infection in the samples performs well when used repeatedly.

In addition this study will also evaluate the returned TFV rings to see whether they were used as instructed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Condition  ICMJE HIV
Intervention  ICMJE
  • Drug: Tenofovir intravaginal ring
    The participant will wear the intravaginal ring consecutively for 14 days and nights. Following study product use and at study visit 4, blood and genital tract samples will be taken (to include cervico-vaginal fluid and tissue)
    Other Names:
    • Tenofovir disoproxil fumarate intravaginal ring
    • TFV IVR
  • Drug: Truvada
    The participant will take the tablet for 14 days. taking one tablet each morning. Following study product use and at study visit 4, blood and genital tract samples will be taken (to include cervico-vaginal fluid and tissue)
    Other Name: Emtricitabine/tenofovir disoproxil fumarate tablets
Study Arms  ICMJE
  • Experimental: Tenofovir intravaginal ring
    The tenofovir intravaginal ring (TFV IVR) is 55.0 mm in diameter, consisting of a single segment of polyurethane tubing with an outer diameter of 5.5 mm and filled with white TFV-containing paste. The IVR delivers 8-10mg/day of TFV.
    Intervention: Drug: Tenofovir intravaginal ring
  • Active Comparator: Truvada oral tablets
    The tablets contain 200mg emtricitabine combined with 300mg tenofovir disoproxil fumarate (300mg). The tablets are commercially available as Truvada. The tablets are blue, capsule-shaped, film-coated, debossed with "GILEAD" on one side and with "701" on the other side
    Intervention: Drug: Truvada
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 1, 2016)
25
Original Estimated Enrollment  ICMJE
 (submitted: March 23, 2016)
20
Actual Study Completion Date  ICMJE August 2016
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • General good health (by volunteer history and per investigator judgment) without any clinically significant systemic disease (including, but not limited to significant liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, osteoporosis or bone disease, and diabetes) and with an intact gastrointestinal tract, uterus and cervix
  • Currently have regular menstrual cycles of 21-35 days by participant record
  • Willing to abstain from vaginal intercourse and any other vaginal activity including use of vaginal products (tampons, spermicides, lubricants, and douches) other than study products:

    • 48 hours before Visit 2 until six days after Visit 2
    • 48 hours before Visit 3 until six days after Visit 4
  • Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to easy genital tract sample collection
  • Estimated calculated creatinine clearance (eCcr) of at least 60 mL/min
  • History of Pap smears and follow-up consistent with standard clinical practice as outlined in the study manual or willing to undergo a Pap smear at Visit 1
  • Protected from pregnancy by one of the following:

    • sterilization of either partner
    • abstinence
    • same sex relationship
    • condoms
    • combined contraceptives (including oral, patch)
    • copper IUD
  • Willing and able to comply with protocol requirements including swallowing tablets
  • Willing to give voluntary consent and sign an informed consent form

Exclusion Criteria:

  • History of hysterectomy
  • Currently pregnant or within two calendar months from the last pregnancy outcome. Note: if recently pregnant must have had at least two spontaneous menses since pregnancy outcome
  • Injection of Depo-Provera in the last 10 months or use of other progestin-only based contraceptive (including hormonal IUD)
  • Currently breastfeeding or planning to breastfeed during the course of the study
  • History of sensitivity/allergy to any component of the study products, topical anesthetic, or to both silver nitrate and Monsel's solution
  • In the last three months, diagnosed with or treated for any STI, by self report
  • Positive test for Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, HIV, or Hepatitis B surface antigen (HBsAg) Note: Women with a history of genital herpes who have been asymptomatic for at least three months may be considered for eligibility
  • Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting/bleeding, discharge, etc.)
  • Known bleeding disorder that could lead to prolonged or continuous bleeding with biopsy
  • Systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants or other drugs known to prolong bleeding and/or clotting, antifungals, or antivirals (e.g., acyclovir, valacyclovir, Viread®, Atripla®, Emtriva®, or Complera®)
  • Current or anticipated chronic use of NSAIDS, or Tylenol for the duration of the study
  • Grade 2 or higher laboratory abnormality, per the 2014 update of the Division of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse Events, or clinically significant laboratory abnormality as determined by the clinician
  • Abnormal finding on laboratory or physical examination or a social or medical condition in either the volunteer or which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data
  • Known current drug or alcohol abuse which could impact study compliance
  • Participation in any other investigational trial within the last 30 days or planned participation in any other investigational trial during the study
  • History of gynecological procedures (including genital piercing) on the external genitalia, vagina or cervix within the last 14 days
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02722343
Other Study ID Numbers  ICMJE A15-140
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party CONRAD
Study Sponsor  ICMJE CONRAD
Collaborators  ICMJE
  • Eastern Virginia Medical School
  • University of North Carolina
  • Agility Clinical, Inc.
Investigators  ICMJE
Principal Investigator: Andrea R Thurman, M.D. Eastern Virginia Medical School
PRS Account CONRAD
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP