Safety and Pharmacokinetics (PK) of a Polyurethane Tenofovir Disoproxil Fumarate (TDF) Vaginal Ring
Condition: HIV
Intervention: TDF Intravaginal Ring; Placebo Intravaginal Ring
Intervention description: The TDF IVR intravaginal ring is formulated using flexible outer tubing, comprised of hydrophilic, aliphatic polyether urethane, and an inner core compartment comprised of 86% w/w TDF and 14% w/w sodium chloride (NaCl). The TDF intravaginal ring will be worn continuously for 14 days. It will be inserted into the vagina following cessation of participant's menses at Visit 3 and removed at Visit 7.; The placebo ring is formulated using flexible outer tubing, comprised of hydrophilic, aliphatic polyether urethane, and an inner core comprised of sodium chloride (NaCl). The Placebo intravaginal ring will be worn continuously for 14 days. It will be inserted into the vagina following cessation of participant's menses at Visit 3 and removed at Visit 7.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 30.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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.
    

Eligibility 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 (Center for Disease Control and Prevention) 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.