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

NCT02006264 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2013-329U19AI076980
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV

Outcome Measures

Primary Outcomes (2)

• Grade 1 Genitourinary Events or Higher as Defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events

  Grade 1 or higher Genitourinary events as defined by the DAIDS (Division of AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events during the trial period judged to be related to study product

  14 days of vaginal ring use

• Grade 2 or Higher Adverse Events as Defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events

  Grade 2 or higher systemic and local Adverse Events as defined by the Division of Aids (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events during the trial period

  14 days of vaginal ring use

Secondary Outcomes (5)

• TDF and TFV Maximum Concentrations (C-max) in CVF Genital Secretions (ECX and VAG) and TFV Maximum Concentration in Plasma

  1, 3, 7 and 14 days after ring insertion and 2 and 7 days after ring removal

• TDF and TFV Time to Maximum Concentrations (T-max) in CVF Genital Secretions (ECX and VAG), and TFV Time to Maximum Concentration in Plasma

  1, 3, 7 and 14 days after ring insertion and 2 and 7 days after ring removal

• TDF AUC0-14 in CVF Genital Secretions (ECX and VAG), TFV AUC0-14 in CVF Genital Secretions (ECX and VAG), and TFV AUC0-14 in Plasma

  1, 3, 7 and 14 days after ring insertion and 2 and 7 days after ring removal

• TFV C-ave in Cervical Tissue

  before and after 14 days of vaginal ring use

• TFV-DP C-ave in Cervical Tissue

  before and after 14 days of vaginal ring use

Study Arms (2)

TDF Intravaginal Ring

ACTIVE COMPARATOR

Tenofovir Disoproxil Fumarate intravaginal ring (TDF-IVR) is a white (with clear segment), flexible torus-shaped device with an inner core compartment comprised of TDF (86 wt% of formulation) and Sodium Chloride (NaCl) (14 wt% of formulation). The 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.

Drug: TDF Intravaginal Ring

Placebo Intravaginal Ring

PLACEBO COMPARATOR

The placebo intravaginal ring (IVR) is a clear, flexible torus-shaped device with an inner core which contains sodium chloride (NaCl). The 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.

Drug: Placebo Intravaginal Ring

Interventions

TDF Intravaginal Ring DRUG

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.

Also known as: TDF IVR

TDF Intravaginal Ring

Placebo Intravaginal Ring DRUG

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.

Also known as: Placebo

Placebo Intravaginal Ring

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Related Publications (2)

• Smith JM, Rastogi R, Teller RS, Srinivasan P, Mesquita PM, Nagaraja U, McNicholl JM, Hendry RM, Dinh CT, Martin A, Herold BC, Kiser PF. Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges. Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16145-50. doi: 10.1073/pnas.1311355110. Epub 2013 Sep 16.

  PMID: 24043812 BACKGROUND

• Mesquita PM, Rastogi R, Segarra TJ, Teller RS, Torres NM, Huber AM, Kiser PF, Herold BC. Intravaginal ring delivery of tenofovir disoproxil fumarate for prevention of HIV and herpes simplex virus infection. J Antimicrob Chemother. 2012 Jul;67(7):1730-8. doi: 10.1093/jac/dks097. Epub 2012 Mar 30.

  PMID: 22467632 BACKGROUND

Results Point of Contact

• Title: Marla Keller, MD, Principal Investigator
• Organization: Albert Einstein College of Medicine

marla.keller@einstein.yu.edu

718-430-3240

Study Officials

• Marla J Keller, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dept of Medicine

Study Record Dates

• First Submitted: November 19, 2013
• First Posted: December 10, 2013
• Study Start: November 19, 2013
• Primary Completion: November 6, 2014
• Study Completion: November 6, 2014
• Last Updated: August 28, 2018
• Results First Posted: August 28, 2018

Record last verified: 2018-07

Locations

US (1)