Safety and Pharmacokinetics (PK) of a Polyurethane Tenofovir Disoproxil Fumarate (TDF) Vaginal Ring (TDF IVR-001)

This study is currently recruiting participants.
Verified December 2013 by Albert Einstein College of Medicine of Yeshiva University
Sponsor:
Information provided by (Responsible Party):
Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier:
NCT02006264
First received: November 19, 2013
Last updated: December 5, 2013
Last verified: December 2013
  Purpose

This prospective, randomized, single-blinded, placebo controlled trial will examine the safety and pharmacokinetics (PK) of a polyurethane tenofovir disoproxil fumarate (TDF) vaginal ring when used continuously for 14 consecutive days.

The primary objective is to assess the safety of TDF vaginal rings when used continuously for 14 days by healthy, HIV-uninfected, sexually abstinent women, as compared with a placebo vaginal ring.


Condition Intervention Phase
HIV
Drug: TDF Intravaginal Ring
Drug: Placebo Intravaginal Ring
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Official Title: Phase 1 Safety and Pharmacokinetic Study of Polyurethane Tenofovir Disoproxil Fumarate Vaginal Ring

Resource links provided by NLM:


Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • Genitourinary events Grade 1 or higher judged to be related to study product. [ Time Frame: 14 days of vaginal ring use ] [ Designated as safety issue: Yes ]
    Adverse Events as defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events

  • Adverse events Grade 2 or higher [ Time Frame: 14 days of vaginal ring use ] [ Designated as safety issue: Yes ]
    Adverse Events as defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events


Secondary Outcome Measures:
  • TDF and TFV concentrations in plasma and genital secretions (cervix and vagina) [ Time Frame: Days 1, 3, 7 and 14 after ring insertion and 2 and 7 days after ring removal. ]
    TDF and TFV concentrations in plasma and genital secretions pharmacokinetics (C-Max, T-Max and AUC)

  • TFV and tenofovir diphosphate (TFV-DP) concentrations in PBMCs [ Time Frame: Days 1, 3, 7 and 14 after ring insertion and 2 and 7 days after ring removal. ]
    TFV and tenofovir diphosphate (TFV-DP) concentrations in PBMCs pharmacokinetics (C-Max, T-Max and AUC)

  • TFV and TFV-DP concentrations in cervical tissue [ Time Frame: 14 days after vaginal ring insertion ]
    TFV and TFV-DP concentrations in cervical tissue pharmacokinetics (C-Max, T-Max and AUC)


Estimated Enrollment: 30
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: TDF Intravaginal Ring Drug: TDF Intravaginal Ring
Placebo Comparator: Placebo Intravaginal Ring Drug: Placebo Intravaginal Ring

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • General good health (by volunteer history and per investigator discretion) 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)
  • Willing to give voluntary consent, sign an informed consent form and comply with study procedures as required by the protocol
  • HIV-uninfected based on testing performed by study staff during screening procedures
  • Using low dose combined (estrogen and progesterone-containing) oral contraceptive pills (does not include extended-cycle, 24 and 28-day active pill regimens). Per participant report must be using this contraceptive method with no change in the prior 3 months and intending to use same method for the duration of study participation.
  • Currently have a regular 28-day menstrual cycle on combined oral contraceptive pills.
  • Normal Pap test at screening or appropriately documented history of Pap test and completed follow-up of any abnormal pap tests consistent with American Congress of Obstetricians and Gynecologists (ACOG) practice guidelines #99 and #109.
  • Agrees not to participate in other research studies involving drugs, medical devices, or vaginal products for the duration of study participation.
  • Able and willing to refrain from inserting any non-study vaginal products or objects into the vagina for the 48 hours prior to Visit 2 throughout the duration of the study.
  • Able and willing to abstain from oral, vaginal and anal sex for 48 hours prior to Visit 2 throughout the duration of the study.

Exclusion Criteria:

Women must meet none of the following criteria prior to genital sampling at Visit 2:

  • Known adverse reaction to polyurethane or to any components of the study product or allergy to both silver nitrate and Monsel's solution.
  • Hepatitis B infection (defined as positive hepatitis B surface antigen).
  • Chronic, recurrent, and/or acute vulvar or vaginal symptoms (pain, irritation, spotting, etc.).
  • Known bleeding disorder that could lead to prolonged or continuous bleeding with biopsy.
  • Pregnant or intending to become pregnant during the period of study participation.
  • Currently breastfeeding or having breastfed an infant in the last two months, or planning to breastfeed during the course of the study.
  • Menopause.
  • History of unexplained or unresolved intermenstrual bleeding in the 3 months prior to screening.
  • History of gynecological procedures (including genital piercing) on the external genitalia, vagina or cervix in the last 14 days.
  • Hysterectomy.
  • Use and/or anticipated use during the study period of an intravaginal or intrauterine device.
  • Systemic use in the last 2 weeks or anticipated use during the study period of any of the following: corticosteroids, antibiotics, antifungals, antivirals, anticoagulants or antiretrovirals.
  • Grade 1 or higher laboratory abnormality, per the August 2009 update of the Division of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse Events (AEs).
  • In the last six months, diagnosed with or treated for any sexually transmitted infection (STI).
  • Reproductive tract infection (RTI) or pelvic inflammatory disease (PID) requiring treatment per current CDC guidelines at Screening or Enrollment.
  • Positive test for Trichomonas vaginalis, Neisseria gonorrhea or Chlamydia trachomatis at screening.
  • Reactive test for syphilis at screening.
  • At Screening or Enrollment, has a clinically apparent Grade 1 or higher pelvic exam finding (observed by study clinician or designee) per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Addendum 1, Female Genital Grading Table for Use in Microbicide Studies.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02006264

Contacts
Contact: Lilia Espinoza 718-430-3061 lilia.espinoza@einstein.yu.edu

Locations
United States, New York
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Lilia Espinoza    718-430-3061    lilia.espinoza@einstein.yu.edu   
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
  More Information

Publications:
Responsible Party: Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier: NCT02006264     History of Changes
Other Study ID Numbers: 2013-329
Study First Received: November 19, 2013
Last Updated: December 5, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Department of Health and Human Services

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

ClinicalTrials.gov processed this record on April 15, 2014