Promising safety and pharmacokinetic data on BT051 for UC

BT051, a drug in clinical development for the treatment of ulcerative colitis (UC), was safe and well tolerated in the healthy subject population of a phase 1, randomised, double-blind trial. Moreover, the drug demonstrated very limited systemic exposure. The results support the further development of BT051 as a potential gut-targeted therapy for patients with UC.

BT051 is an oral, non-systemic, multidrug resistance-associated protein 2 (MRP2)/formyl peptide receptor 1 (FRP1) antagonist. The drug targets gut neutrophil activity. To assess the safety, tolerability, and pharmacokinetics of BT051, healthy subjects were enrolled in five BT051 ascending single-dose cohorts (n=40) or placebo (n=10) [1]. The lowest administered dose was 100 mg, the highest dose was 3,500 mg. Participants were followed until 30 days post-dose.

Adverse events (AEs) occurred equally often in the BT051 cohorts and placebo group, with 22.5% and 20% of the subjects, respectively, experiencing at least 1 AE. No serious AEs or study discontinuations due to AEs were reported. In addition, no dose-limiting toxicities were observed for the BT051 cohorts. Moreover, systemic exposure was not quantifiable in most subjects. Only 2 subjects showed 1 quantifiable blood sample each. The mean percentage of BT051 excreted through faeces ranged between 10.2% and 23.7%. This suggests that BT051 is primarily excreted in the faeces. The mean percentage of BT051 excreted in urine was 0.01-0.03%. Importantly, concentrations of BT051 in the large intestine showed limited gut absorption after oral dosing. Immunosuppression through circulating T-cells was not observed for any dose.

1. Stevens C, et al. Safety, tolerability and pharmacokinetics of BT051, an oral inhibitor of neutrophil migration and activation in clinical development for Inflammatory Bowel Disease. P259, ECCO 2021 Virtual Congress, 2-3 & 8-10 July.

 

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Posted on 2 July 20218 April 2024