A Phase I Clinical Trial Assessing the Safety, Pharmacokinetics, Pharmacodynamics, and Disintegration Time of Vaginal Tablets Containing Tenofovir and/or Emtricitabine

CONRAD2 sites in 1 country48 target enrollmentFebruary 2013

ConditionsHIV

InterventionsTenofovir (TFV) Alone Vaginal Tablet Emtricitabine (FTC) Alone Vaginal Tablet TFV and FTC Combined Vaginal Tablet Placebo Vaginal Tablet

DrugsTenofovir (TFV) Alone Vaginal Tablet Emtricitabine (FTC) Alone Vaginal Tablet TFV and FTC Combined Vaginal Tablet Placebo Vaginal Tablet

Overview

Phase: Phase 1
Intervention: Tenofovir (TFV) Alone Vaginal Tablet
Conditions: HIV
Sponsor: CONRAD
Enrollment: 48
Locations: 2
Primary Endpoint: Changes in Genitourinary AEs
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This prospective, double-blinded, randomized, parallel cohort study will examine the genital and systemic safety, pharmacokinetics (PK), pharmacodynamics (PD), disintegration and disappearance times, and acceptability of four vaginal tablets: 1) Tenofovir (TFV) alone; 2) Emtricitabine (FTC) alone; 3) TFV combined with FTC; and 4) placebo. Participants will be randomized to treatment group, to number of tablets to be inserted in the Single Use Phase (1 tablet or 1 tablet followed by a second tablet two hours later to mimic the BAT24 dosing regimen), and to one of four collection time points (2, 4, 6, or 24 hours after tablet insertion) for assessments only after the last dose of the Multiple Use Phase.

In the Single Use Phase of the study, the participant will insert one tablet in the clinic to estimate times to disintegration and disappearance. Those randomized to two tablets will insert a second tablet 2 hours later. In all women, sample collection will occur 5 hours after the initial tablet insertion.

In the Multiple Use Phase of the study, participants will insert a tablet once daily for 14 days. The 1st, 7th, and 14th tablets will be inserted in the clinic; the remaining tablets will be inserted at home. The clinic will call the participant on day 3 of the multiple use phase to ask about any symptoms the participant may be experiencing. Each insertion in the clinic will be followed by sample collection and, at Visits 4 and 6, colposcopy at the participant's assigned time point.

Detailed Description

Objectives: Primary: * To assess genital safety after a single use (consisting of one tablet in half of participants and one tablet followed by a second tablet two hours later in the other half) and during and after two weeks of daily tablet use * To assess systemic safety after two weeks of daily tablet use * To assess the pharmacokinetics (PK) of TFV and FTC after a single use (as defined above) and during and after two weeks of daily tablet use Secondary: * To estimate the time needed for tablet disintegration and the time needed for full tablet disappearance * To assess acceptability of the tablet * To assess indicators of the pharmacodynamics (PD) of TFV and FTC in vitro using biological samples (fluids) from study participants obtained before use, after a single (use as define above), and after two weeks of daily tablet use Exploratory: •To assess exploratory indicators of the PD of TFV and FTC in vitro using biological samples (tissues) from study participants obtained before use, after a single use (as defined above), and after two weeks of daily tablet use

Registry

clinicaltrials.gov

Start Date

February 2013

End Date

December 2013

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

CONRAD

Responsible Party

Sponsor

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)
•Currently having regular menstrual cycles of 25 - 35 days by participant report
•History of Pap smears and follow-up consistent with American Congress of Obstetricians and Gynecologist (ACOG) practice guidelines #99 and #109 or willing to undergo a Pap smear at Visit 1
•Protected from pregnancy, meaning one of the following:
•Sexually abstinent and planning to remain abstinent for the duration of the study;
•In a monogamous heterosexual relationship for at least four months with a partner who is not known to be HIV positive and has no known risks for sexually transmitted infections (STIs) and:
•Couple is using condoms and is willing to use non-spermicidally lubricated condoms throughout the study or
•One partner is sterilized; or
•In a monogamous same sex relationship for at least four months with a partner who is not known to be HIV positive and has no known risks for STIs.
•Willing to abstain from vaginal activity as follows:

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
•Use of any hormonal contraceptive method in the last 30 days (oral, transdermal, transvaginal, implant, or hormonal intrauterine contraceptive device)
•Injection of Depo-Provera in the last 6 months
•Current use of IUD
•Currently breastfeeding or having breastfed an infant in the last two months, or planning to breastfeed during the course of the study
•History of sensitivity/allergy to any component of the study products, topical anesthetic, or allergy to both silver nitrate and Monsel's solution
•In the last six months, diagnosed with or treated for any STI or pelvic inflammatory disease. Note: Women with a history of genital herpes or condylomata who have been asymptomatic for at least six months may be considered for eligibility
•Nugent score greater than or equal to 7 at Visit 1 or symptomatic bacterial vaginosis (BV) as defined by Amsel's criteria at Visit 1 or 2
•Symptomatic vulvovaginal candidiasis or symptomatic urinary tract infection (UTI)

Arms & Interventions

TFV Alone Vaginal Tablet

Intervention: Tenofovir (TFV) Alone Vaginal Tablet

Emtricitabine (FTC) Alone Vaginal Tablet

Intervention: Emtricitabine (FTC) Alone Vaginal Tablet

TFV Combined with FTC Vaginal Tablet

Intervention: TFV and FTC Combined Vaginal Tablet

Placebo Vaginal Tablet

Intervention: Placebo Vaginal Tablet