Abstract
Background: Remdesivir is a novel broad-spectrum antiviral therapeutic with activity against several viruses that cause emerging infectious diseases. The purpose of this study is to explore how commonly utilized antiretroviral therapy (tenofovir disoproxil fumarate /lamivudine [TDF/3TC] and atazanavir/ritonavir [ATV/r]) influence plasma and intracellular concentrations of remdesivir. Methods: This is an open label, randomized, fixed sequence single intravenous dosing study to assess pharmacokinetic interactions between remdesivir and TDF/3TC (Study A, Crossover design) or TDF/3TC plus ATV/r (Study B). Healthy volunteers satisfying study entry criteria will be enrolled in the study and randomized to either Study A; N=16 (Sequence 1 or Sequence 2) or Study B; N=8. Participants will receive standard adult doses of antiretroviral therapy for seven days and a single 200mg remdesivir infusion administered over 60 minutes. Pharmacokinetic blood sampling will be performed relative to start of remdesivir infusion; predose (before start of remdesivir infusion) and 30 minutes after start of remdesivir infusion. Additional blood samples will be taken at 2, 4, 6, 12 and 24 hours after end of remdesivir infusion. Discussion: This study will characterize the pharmacokinetics of remdesivir from a typical African population in whom clinical use is anticipated. Furthermore, this study will deliver pharmacokinetic datasets for remdesivir drug concentrations and demographic characteristics which could support pharmacometric approaches for simulation of remdesivir treatment regimens in patients concurrently using tenofovir/lamivudine and/or atazanavir/ritonavir. Trial registration: ClinicalTrials.gov, ID:NCT04385719
A Phase 1 Open-Label Fixed-Sequence Two-Period Crossover Study of the Effect of Multiple Doses of Tamoxifen on Palbociclib (PD-0332991) Pharmacokinetics in Healthy Male Volunteers