NCT04385719

Drug-drug Interactions Between Remdesivir and Commonly Used Antiretroviral Therapy

An Open-label, Randomized, Single Intravenous Dosing Study to Investigate the Effect of Fixed-dose Combinations of Tenofovir/Lamivudine or Atazanavir/Ritonavir on the Pharmacokinetics of Remdesivir in Ugandan Healthy Volunteers

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Makerere University · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

Ebola and HIV are found predominately in the same regions of the world and countries in sub-Saharan Africa are most affected by both diseases. For Ebola, no approved therapies exist. However, new investigational drugs are being evaluated to understand if they are effective against the Ebola virus. Remdesivir is an anti-Ebola investigational drug for the treatment of Ebola. Little is known about how the blood levels of remdesivir relate to how effective it is in patients with HIV taking antiretroviral therapy. This study will explore how commonly utilized ART (tenofovir/lamivudine and atazanavir/ritonavir) affect the drug levels of remdesivir.

Detailed description

The study is designed as an open-label, randomized, fixed sequence, single intravenous dosing study to assess the effects of antiretrovirals on remdesivir pharmacokinetics. The selection of healthy volunteers, as opposed to patients with HIV, avoids the greatest possible extent confounding factors, such as enzyme or transporter activity alteration in inflammatory states, concomitant medications potentially impacting drug disposition and other factors which are commonly present in a population of patients and cannot be easily eliminated. Objectives: Primary objective 1. To assess the safety and tolerability of single intravenous doses of remdesivir in adult healthy volunteers 2. To evaluate the intracellular pharmacokinetics of single dose intravenous remdesivir with or without co-administration of oral fixed-dose combination tenofovir/lamivudine with patients serving as their own controls Secondary objectives 1. To evaluate the difference in plasma and intracellular pharmacokinetics of intravenous remdesivir among healthy volunteers receiving tenofovir/lamivudine versus healthy volunteers receiving tenofovir/lamivudine plus atazanavir/ritonavir tablets. 2. To generate a population pharmacokinetic model to describe inter-individual variability in intracellular pharmacokinetics of remdesivir Exploratory objectives 1\. To describe polymorphic variants of relevant kinases that activate TFV and explore possible consequences on remdesivir PK.

Conditions

• Ebola
• HIV/AIDS

Interventions

Type	Name	Description
DRUG	Remdesivir	Remdesivir (GS-5734) is a nucleoside analogue with in vitro activity against filoviruses EBOV, SUDV, BDBV and MARV, in addition to arenaviruses and coronaviruses

Timeline

• Start date: 2021-05-05
• Primary completion: 2021-07-02
• Completion: 2021-07-16
• First posted: 2020-05-13
• Last updated: 2021-08-25

Locations

1 site across 1 country: Uganda