Impact of Weekly Administration of Rifapentine and Isoniazid on Steady State Pharmacokinetics of Tenofovir Alafenamide in Healthy Volunteers (YODA)

Summary

Participation Requirements

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...

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 firstline 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.

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