# Single-ascending and multiple-ascending dose study of the pharmacokinetics, safety, and tolerability of BV100 (rifabutin for infusion) in healthy volunteers

## TL;DR

This study tested the safety and effectiveness of a new intravenous drug for treating severe infections caused by a drug-resistant bacteria in healthy volunteers.

## Contribution

The study provides new pharmacokinetic data and safety profile for BV100, an intravenous formulation of rifabutin for treating carbapenem-resistant Acinetobacter baumannii.

## Key findings

- BV100 showed a dose-proportional pharmacokinetic profile with a half-life of 7.9–56.1 hours.
- Adverse events were more frequent at higher doses and with longer infusion times.
- BV100 is now being evaluated in a Phase 2 trial for treating carbapenem-resistant A. baumannii infections.

## Abstract

BV100 (rifabutin for infusion) is being developed as an intravenous formulation for treating serious or life-threatening infections due to carbapenem-resistant Acinetobacter baumannii in patients with limited treatment options. Phase 1 studies were conducted to characterize the pharmacokinetics (PK), safety, and tolerability of BV100 in healthy volunteers after single and multiple doses. Single-ascending and multiple-ascending dose studies were conducted in healthy subjects to establish the PK profile of BV100. Blood samples were assayed to determine plasma concentrations of rifabutin and the major metabolite 25-O-desacetyl-rifabutin and to determine PK parameters. Subjects were assessed for safety and tolerability. The PK profile of BV100 was generally dose-proportional in the single-ascending dose studies with a t1/2 of 7.9–56.1 h, and Tmax of 1.0–1.75 h and increasing exposure with dose. A q12h versus q24h dosing interval resulted in approximately a 1.5-fold to 2-fold greater exposure of rifabutin. The 25-O-desacetyl-rifabutin metabolite represented <5% of rifabutin activity. Adverse events were more common at higher doses with q24h versus q12h dosing, and with a 60 min infusion time. The most common adverse events were infusion site events, with systemic treatment-emergent adverse events as expected for the known safety profile of rifabutin. No other treatment-related safety issues were identified. BV100 demonstrated a dose-proportional PK profile and was generally safe and well tolerated. Based on these results, BV100 doses of 200–300 mg q12h are undergoing evaluation in a Phase 2 study for treating carbapenem-resistant A. baumannii infections.

This study is registered with ClinicalTrials.gov as NCT04636983 and NCT05087069.