Exploratory Pharmacodynamic Study of Tenofovir-Based Products

NCT02722343 | Completed Phase 1

• 1 other identifier: A15-140
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This single site study is designed to describe and measure the efficacy of oral versus vaginal dosing of TFV-based products, specifically emtricitabine/tenofovir disoproxil fumarate oral tablets (Truvada) vs tenofovir intravaginal rings (IVR).

Conditions

HIV

Outcome Measures

Primary Outcomes (3)

• p24 antigen production in cervico-vaginal tissues infected with HIV

  • Assess p24 antigen production in cervicovaginal tissues infected ex vivo with HIV-1BaL at baseline and after using Truvada tablets or tenofovir intravaginal ring

  Day 14

• Analysis of integrated DNA

  Integrated viral DNA in cervicovaginal tissues infected ex vivo with HIV-1BaL at baseline and after using Truvada tablets or tenofovir intravaginal ring

  Day 14

• Anti-HIV activity in cervicovaginal fluid (CVF)

  Anti-HIV activity in cervicovaginal fluid at baseline and after using Truvada tablets and tenofovir intravaginal ring

  Day 14

Secondary Outcomes (5)

• Cervicovaginal tissue, fluid and plasma concentrations of tenofovir

  Day 14

• Cervicovaginal tissue concentration of tenofovir diphosphate

  Day 14

• Cervicovaginal tissue, fluid and plasma concentrations of emtricitabine

  Day 14

• Cervicovaginal tissue concentration of emtricitabine triphosphate

  Day 14

• Endogenous nucleotide concentrations in cervicovaginal tissue

  Day 14

Other Outcomes (1)

• Adherence markers in used IVRs

  Day 14

Study Arms (2)

Tenofovir intravaginal ring

EXPERIMENTAL

The tenofovir intravaginal ring (TFV IVR) is 55.0 mm in diameter, consisting of a single segment of polyurethane tubing with an outer diameter of 5.5 mm and filled with white TFV-containing paste. The IVR delivers 8-10mg/day of TFV.

Drug: Tenofovir intravaginal ring

Truvada oral tablets

ACTIVE COMPARATOR

The tablets contain 200mg emtricitabine combined with 300mg tenofovir disoproxil fumarate (300mg). The tablets are commercially available as Truvada. The tablets are blue, capsule-shaped, film-coated, debossed with "GILEAD" on one side and with "701" on the other side

Drug: Truvada

Interventions

Tenofovir intravaginal ring DRUG

The participant will wear the intravaginal ring consecutively for 14 days and nights. Following study product use and at study visit 4, blood and genital tract samples will be taken (to include cervico-vaginal fluid and tissue)

Also known as: Tenofovir disoproxil fumarate intravaginal ring, TFV IVR

Tenofovir intravaginal ring

Truvada DRUG

The participant will take the tablet for 14 days. taking one tablet each morning. Following study product use and at study visit 4, blood and genital tract samples will be taken (to include cervico-vaginal fluid and tissue)

Also known as: Emtricitabine/tenofovir disoproxil fumarate tablets

Truvada oral tablets

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General good health (by volunteer history and per investigator judgment) 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) and with an intact gastrointestinal tract, uterus and cervix
• Currently have regular menstrual cycles of 21-35 days by participant record
• Willing to abstain from vaginal intercourse and any other vaginal activity including use of vaginal products (tampons, spermicides, lubricants, and douches) other than study products:
• hours before Visit 2 until six days after Visit 2
• hours before Visit 3 until six days after Visit 4
• Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to easy genital tract sample collection
• Estimated calculated creatinine clearance (eCcr) of at least 60 mL/min
• History of Pap smears and follow-up consistent with standard clinical practice as outlined in the study manual or willing to undergo a Pap smear at Visit 1
• Protected from pregnancy by one of the following:
• sterilization of either partner
• abstinence
• same sex relationship
• condoms
• combined contraceptives (including oral, patch)
• copper IUD

You may not qualify if:

• 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
• Injection of Depo-Provera in the last 10 months or use of other progestin-only based contraceptive (including hormonal IUD)
• Currently breastfeeding or planning to breastfeed during the course of the study
• History of sensitivity/allergy to any component of the study products, topical anesthetic, or to both silver nitrate and Monsel's solution
• In the last three months, diagnosed with or treated for any STI, by self report
• Positive test for Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, HIV, or Hepatitis B surface antigen (HBsAg) Note: Women with a history of genital herpes who have been asymptomatic for at least three months may be considered for eligibility
• Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting/bleeding, discharge, etc.)
• Known bleeding disorder that could lead to prolonged or continuous bleeding with biopsy
• Systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants or other drugs known to prolong bleeding and/or clotting, antifungals, or antivirals (e.g., acyclovir, valacyclovir, Viread®, Atripla®, Emtriva®, or Complera®)
• Current or anticipated chronic use of NSAIDS, or Tylenol for the duration of the study
• Grade 2 or higher laboratory abnormality, per the 2014 update of the Division of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse Events, or clinically significant laboratory abnormality as determined by the clinician
• Abnormal finding on laboratory or physical examination or a social or medical condition in either the volunteer or which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data
• Known current drug or alcohol abuse which could impact study compliance
• Participation in any other investigational trial within the last 30 days or planned participation in any other investigational trial during the study

Sponsors & Collaborators

• CONRAD: lead
• Eastern Virginia Medical School: collaborator
• University of North Carolina: collaborator
• Agility Clinical, Inc.: collaborator

Study Sites (1)

Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

Related Publications (1)

• Ouattara LA, Thurman AR, Jacot TA, Cottrell M, Sykes C, Blake K, Fang X, Ju S, Vann NC, Schwartz J, Doncel GF. Genital Mucosal Drug Concentrations and anti-HIV Activity in Tenofovir-Based PrEP Products: Intravaginal Ring vs. Oral Administration. J Acquir Immune Defic Syndr. 2022 Jan 1;89(1):87-97. doi: 10.1097/QAI.0000000000002820.

  PMID: 34878438 DERIVED

MeSH Terms

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Tenofovir

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Andrea R Thurman, M.D.

  Eastern Virginia Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: March 30, 2016
• Study Start: April 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: September 2, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)