ClinicalTrials.gov
ClinicalTrials.gov Menu

PK and PD Study of Oral F/TAF for HIV Prevention

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02904369
Recruitment Status : Completed
First Posted : September 19, 2016
Last Update Posted : February 19, 2018
Sponsor:
Collaborators:
United States Agency for International Development (USAID)
Agility Clinical, Inc.
Information provided by (Responsible Party):
CONRAD

Brief Summary:
This multi-center Phase I study is designed to characterize the PK and PD of F/TAF oral tablets to assess systemic and genital tract bioavailability in healthy women. The oral tablets to be used in the study are F/TAF (200/10 mg), F/TAF (200/25 mg) and F/TDF (200/300 mg, Truvada). Samples will be obtained before, during and after dosing in two study phases.

Condition or disease Intervention/treatment Phase
HIV Drug: Emtricitabine Drug: Tenofovir alafenamide Drug: Tenofovir disoproxil Phase 1

Detailed Description:

The purpose of this multi-center Phase I protocol, titled Exploratory Pharmacokinetic and Pharmacodynamic Study of Oral F/TAF for the Prevention of HIV Acquisition is to assess local and systemic pharmacokinetics (PK), pharmacodynamics (PD), and safety characteristics of three oral tablets: F/TAF (200/10 mg), F/TAF (200/25 mg) and F/TDF (200/300 mg).

The study will enroll healthy, non-pregnant, HIV negative, premenopausal women (aged 18-50) who are not at risk of pregnancy and will have two phases: a Single Dose phase (one site only) and a Multiple Dose phase (all three sites).

The enrollment goal is for approximately 72 participants to complete the study. All 72 women are expected to undergo the Multiple Dose phase and the 24 women expected to complete the study at the EVMS site are also expected to undergo the Single Dose phase.

In the Single Dose phase, approximately 24 women will be randomized to one of two products: F/TAF (200/25 mg) or F/TDF (200/300 mg), and will undergo blood, cervicovaginal (CV), and rectal sample collections before and after a single dose for PK and PD assessments. In the Multiple Dose phase, approximately 72 women will be randomized to one of three products: F/TAF (200/10 mg), F/TAF (200/25 mg) or F/TDF (200/300 mg), and will undergo blood, CV, and rectal sample collections for PK and PD assessments before, during and after two weeks of daily dosing.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 73 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Exploratory Pharmacokinetic and Pharmacodynamic Study of Oral F/TAF for the Prevention of HIV Acquisition
Actual Study Start Date : October 6, 2016
Actual Primary Completion Date : November 21, 2017
Actual Study Completion Date : November 21, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: F/TAF 200/10
Emtricitabine (FTC) + Tenofovir Alafenamide (TAF) (200/10 mg)
Drug: Emtricitabine
Drug: Tenofovir alafenamide
Experimental: F/TAF 200/25
Emtricitabine (FTC) + Tenofovir Alafenamide (TAF) (200/25 mg)
Drug: Emtricitabine
Drug: Tenofovir alafenamide
Active Comparator: F/TDF 200/300
Emtricitabine (FTC) + Tenofovir Disoproxil Fumarate (TDF) (200/300 mg)
Drug: Emtricitabine
Drug: Tenofovir disoproxil



Primary Outcome Measures :
  1. Plasma, cervicovaginal and rectal fluid concentrations of tenofovir alafenamide (TAF), tenofovir (TFV), and emtricitabine (FTC) [ Time Frame: Day 17 ]
    Concentrations after use of study tablets after single dose, and during (plasma) and after two weeks of daily dosing

  2. PBMC concentrations of tenofovir-diphosphate (TFV-DP), emtricitabine-triphosphate (FTC-TP), deoxyadenosine triphosphate (dATP) and deoxycytidine triphosphate (dCTP) [ Time Frame: Day 17 ]
    Concentrations after use of study tablets after single dose, and during and after two weeks of daily dosing

  3. Cervicovaginal tissue concentrations of TAF, TFV, FTC, TFV-DP, FTC-TP, dATP and dCTP [ Time Frame: Day 17 ]
    Concentrations after use of study tablets after single dose, and after two weeks of daily dosing

  4. Pharmacokinetic parameter (Cmax) of F/TAF in the systemic compartment [ Time Frame: Day 17 ]
    Concentrations after use of study tablets after single dose, and during and after two weeks of daily dosing

  5. p24 antigen production in cervicovaginal and rectal tissue infected with HIV [ Time Frame: Day 17 ]
    p24 antigen production in CV tissue infected with HIV ex vivo after a single dose, and in CV and rectal tissue infected with HIV ex vivo after two weeks of daily dosing compared to baseline

  6. Anti-HIV activity in cervicovaginal and rectal fluid (TZM-bl inhibition measured as mean percent reduction compared to control) [ Time Frame: Day 17 ]
    Anti-HIV activity in CV and rectal fluid after a single dose, and after two weeks of daily dosing compared to baseline

  7. Pharmacokinetic parameter (Tmax) of F/TAF in the systemic compartment [ Time Frame: Day 17 ]
    Concentrations after use of study tablets after single dose, and during and after two weeks of daily dosing

  8. Pharmacokinetic parameter (AUC) of F/TAF in the systemic compartment [ Time Frame: Day 17 ]
    Concentrations after use of study tablets after single dose, and during and after two weeks of daily dosing


Secondary Outcome Measures :
  1. Number of participants with Grade 2 or higher adverse events [ Time Frame: Baseline, Day 17 ]
    Changes from baseline in adverse events


Other Outcome Measures:
  1. Anti-HSV activity in cervicovaginal and rectal fluid (mean percentage inhibition of plaque forming units (pfu) in Vero cells infected with HSV-2) [ Time Frame: Baseline, Day 17 ]
    Anti-HSV activity in CV and rectal fluid after a single dose, and after two weeks of daily dosing compared to baseline

  2. Number of participants with gastrointestinal adverse events [ Time Frame: Baseline, Day 17 ]
    Changes from baseline in adverse events

  3. Number of participants with systemic safety laboratory abnormalities [ Time Frame: Baseline, Day 17 ]
    Changes from baseline in safety laboratory abnormalities



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18 to 50 years, inclusive
  • 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.
  • History of regular menstrual cycles (for cycling women), by volunteer report
  • Estimated calculated creatinine clearance (eCcr) of at least 80 mL/min
  • Body Mass Index (BMI) of ≥18 and <35kg/m2; and a total body weight >45 kg (99.2 lbs)
  • 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
  • Willing to give voluntary consent and sign an informed consent form
  • Willing and able to comply with protocol requirements, including swallowing tablets
  • May not be using progestin-only hormonal contraception and must be protected from pregnancy by:

    • Condoms
    • Combined hormonal contraceptive (acceptable, but recruitment efforts should be made to limit as much as possible the number of women using them in the study, such that they do not represent the majority of participants.)
    • Copper IUD
    • Sterilization of either partner
    • Heterosexual abstinence
    • Same sex relationship
  • If in a relationship, must be in a mutually monogamous relationship with a partner who is not known to be HIV positive and has no known risk of sexually transmitted infections (STIs)

Exclusion Criteria:

  • Currently pregnant
  • 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
  • Positive test for Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, HIV, or Hepatitis B surface antigen (HBsAg)
  • Symptomatic bacterial vaginosis (BV)
  • Current, active Hepatitis C infection
  • 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 or antiretrovirals (e.g. acyclovir, valacyclovir, Viread®, Atripla®, Emtriva®, or Complera®), or drugs that may interact with TAF (e.g., protease inhibitors, anticonvulsants, antimycobacterials, St. John's Wort). See Table 1 from the Patient Information brochure below:
  • Current or anticipated chronic use of NSAIDs or Tylenol for the duration of the study
  • Positive urine drug screen, or known current drug or alcohol abuse which could impact study compliance. Note: therapeutic use of benzodiazepines is acceptable; investigator may discuss with CONRAD participants that may be eligible for enrollment despite a positive drug screen (e.g., false positives, use of cold medications).
  • Participation in any other investigational trial with use of a drug/device within the last 30 days or planned participation in any other investigational with use of a drug/device trial during 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 the volunteer which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02904369


Locations
United States, Pennsylvania
Magee-Womens Research Institute and Foundation
Pittsburgh, Pennsylvania, United States, 15213
United States, Virginia
Eastern Virginia Medical School Clinical Research Center
Norfolk, Virginia, United States, 23507
Dominican Republic
Profamilia
Santo Domingo, Dominican Republic
Sponsors and Collaborators
CONRAD
United States Agency for International Development (USAID)
Agility Clinical, Inc.

Responsible Party: CONRAD
ClinicalTrials.gov Identifier: NCT02904369     History of Changes
Other Study ID Numbers: A15-137
First Posted: September 19, 2016    Key Record Dates
Last Update Posted: February 19, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Tenofovir
Emtricitabine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents