NCT04551573

A Study of the Pharmacokinetic and Pharmacodynamic Interactions Between Bictegravir, Tenofovir Alafenamide and Rifapentine in Healthy Adult Subjects

• Status: Withdrawn
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

This is a single-center, open-label, fixed sequence, pharmacokinetic interaction study between bictegravir and tenofovir alafenamide with rifapentine dosed either daily or weekly. Primary Aims * To assess the effect of once-weekly rifapentine on the steady-state PK of BIC * To assess the effect of once-daily rifapentine on the steady-state PK of BIC Secondary Aims * To assess the effect of daily dosed rifapentine on steady-state PK of TAF (measured as plasma and IC concentrations of TFV-DP) * To assess the effect and timing of interactions of weekly dosed rifapentine on steady-state PK of TAF (measured as plasma and IC concentrations of TFV-DP) * To assess the safety of BIC/TAF/FTC when coadministered with once-weekly or once-daily rifapentine

Detailed description

Subjects will receive once-daily Biktarvy for 4 weeks to ensure all moieties of interest reach steady-state prior to the baseline PK assessment. Thereafter, subjects will be enrolled in one of two groups for PK analysis as follows: Group one will continue Biktarvy and have rifapentine dosed daily for 4 weeks (10 mg/kg; 600mg dose). Group two will continue Biktarvy and have rifapentine dosed weekly for 4 weeks (15 mg/kg; 900mg dose). After 4 weeks of Biktarvy dosing, subjects will have a baseline intensive PK of plasma bictegravir (BIC), tenofovir alafenamide (TAF), tenofovir (TFV) levels at all time points, and peripheral blood mononuclear cells (PBMCs) will be collected at 24 hours post-dose for IC TFV-DP. This will occur prior to receiving their first dose of directly observed oral rifapentine co-administered with Biktarvy, thus serving as their own control. Rifapentine will thereafter be administered by directly observed therapy (DOT) or ingestion monitored by smart phone application (e.g., Time Stamp App or other phone app platform). Intensive PK assessments will be repeated after 4 weeks of RPT dosing for both Group 1 and 2. Intensive PK sampling will be performed at time 0 (pre-dose), 15 and 30 min; 1, 2, 3, 4, 8, 12 and 24 hours post-dose with BIC/TAF/FTC alone and when coadministered with rifapentine. Plasma will be isolated at all time points, and PBMCs will be isolated at 24 hours post-dose. PK levels will be measured by colleagues at the Colorado Antiviral Pharmacology (CAVP) Laboratory at the University of Colorado Anschutz Medical Campus. Plasma concentrations of BIC, TAF, TFV, and IC TFV-DP in PBMCs will be measured by liquid chromatography-tandem mass spectrometry.

Conditions

• Tuberculosis
• Hiv

Interventions

Type	Name	Description
DRUG	Rifapentine daily	In addition to taking Biktarvy for four weeks, participants will also take Rifapentine dosed daily for four weeks (10mg/kg; 600 mg dose)
DRUG	Rifapentine weekly	In addition to taking Biktarvy for four weeks, participants will also take Rifapentine dosed weekly for another four more weeks (15 mg/kg; 900mg dose)

Timeline

• Start date: 2021-05-01
• Primary completion: 2021-10-01
• Completion: 2021-11-01
• First posted: 2020-09-16
• Last updated: 2021-09-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study