Impact of Weekly Administration of Rifapentine and Isoniazid on Steady State Pharmacokinetics of Tenofovir Alafenamide in Healthy Volunteers (YODA)
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      Human immunodeficiency virus (HIV) is treated with antiretroviral drugs. Many people with HIV
      also have the lung infection tuberculosis (TB). Most TB treatments are complicated. A simpler
      treatment of two TB drugs can be taken once a week. Researchers want to study how the HIV and
      TB drugs affect each other so people who take both can be treated safely.

      Objective:

      To study if rifapentine and isoniazid affect blood levels of the common antiretroviral TAF.

      Eligibility:

      Healthy adults ages 18-65 without HIV, TB, or hepatitis

      Design:

      Participants will fast before the screening visit. They will have a medical history, physical
      exam, and blood tests. Women may have a pregnancy test.

      During the study, participants must:

      Use effective birth control

      Not take most medicine

      Not drink alcohol

      At the baseline visit, participants will repeat screening tests and get TAF tablets.

      Participants will take TAF once a day for 31 days. They will keep track of doses and side
      effects.

      Over 32 days, participants will have 4 long visits and 4 short.

      At all visits, participants will:

      Fast the night before

      Get food

      Take that day s TAF

      Review their TAF supply

      Have pregnancy and blood tests

      Report side effects

      At 3 visits, participants will also take the 2 TB drugs and vitamin B6.

      At 3 long visits, participants will also have blood collected 8 times over 8 hours by plastic
      tube in an arm vein.

      Around Day 46, participants will fast and have blood and pregnancy tests. Two weeks later,
      they will get a call to see how they are feeling....
    

Detailed description: 
      Rifapentine (RPT) is a long-acting rifamycin that can be used weekly with isoniazid (INH) as
      a first-line regimen in the treatment of latent tuberculosis infection (LTBI). Although this
      regimen offers several potential benefits, the use of weekly RPT plus INH is limited in
      adults infected with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) due
      to lack of drug interaction data with antiretrovirals (ARVs). Tenofovir alafenamide (TAF) is
      a preferred backbone agent by the current Department of Health and Human Services ARV
      guidelines and is a part of multiple recommended first-line regimens for the treatment of
      HIV. However, the use of TAF with rifamycins, including RPT, is not recommended due to
      potential drug interactions. Thus, the purpose of this study is to determine the effects of
      concomitant RPT and INH administration on the steady state pharmacokinetics (PK) of plasma
      TAF, plasma tenofovir (TFV), and intracellular TFV diphosphate (dp).

      This is an open-label, fixed sequence, intrasubject drug-drug interaction study designed to
      evaluate the steady state PK of TAF, TFV, and TFV-dp with coadministration of once-weekly RPT
      + INH administered at doses used to treat LTBI. The study will consist of two phases: (1) TAF
      once daily alone (days 1-14) and (2) TAF once daily + weight-based RPT + INH once weekly
      (days 15-31). Participants will undergo periodic serial ARV PK blood draws over 24 hours on
      days 14-15, 22-23, and 31-32.

      TAF, TFV, and TFV-dp PK will be determined using non-compartmental methods. The following PK
      parameters will be compared between phases: area under the curve over the dosing interval,
      maximum plasma concentration, time to maximum plasma concentration, terminal half-life,
      apparent oral clearance, and minimum plasma concentration. Adverse events will be graded and
      recorded.
    

Intervention name(s): Tenofovir alafenamide; Rifapentine; Isoniazid (INH); Pyridoxine
Intervention type(s): Drug; Drug; Drug; Dietary Supplement
Intervention description(s): Each tablet contains 25 mg of tenofovir alafenamide.; Each tablet contains 150 mg of rifapentine. Participants who weigh 45 to < 50 kg will take 750 mg (5 tablets), and participants who weigh (Bullet) 50 kg will take 900 mg (6 tablets).; Each tablet is formulated as 100 or 300 mg of isoniazid.; Each tablet contains 50 mg of pyridoxine
Other intervention name(s): Vemlidy; Priftin; Vitamin B6
Intervention MeSH terms: Pyridoxine; Vitamin B 6; Tenofovir; Isoniazid; Rifapentine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Antiretroviral Therapy; Human Immunodeficiency Virus; Latent Tuberculosis; Drug-Drug Interactions; Rifamycin