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

• Status: Completed
• Trial end date: 2014-11-06
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Albert Einstein College of Medicine; Albert Einstein College of Medicine of Yeshiva University
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Tenofovir

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.