A randomized phase I study of the safety and pharmacokinetics of BI 1291583 in healthy Japanese male subjects

Aims Bronchiectasis patients face an unmet need for treatment options that reduce inflammation. Cathepsin C inhibition is expected to achieve this by reducing the activation of neutrophil‐derived serine proteases. Here, we present safety and pharmacokinetic (PK) data from a Phase I trial evaluating the novel cathepsin C inhibitor BI 1291583 in healthy Japanese male subjects. Methods This randomized, double‐blind, placebo‐controlled, parallel‐group study investigated BI 1291583 in healthy Japanese male subjects (jRCT2071210111) and consisted of a single‐rising‐dose (SRD) part and a multiple‐dose (MD) part. The primary endpoint was the percentage of subjects with drug‐related treatment‐emergent adverse events (AEs). Secondary PK endpoints (SRD: AUC 0‐∞ and C max ; MD: AUC τ,1 and C max,1 after first dose and AUC τ,ss and C max,ss after last dose), as well as further safety and PK endpoints, were also assessed. Results Overall, 36 subjects ( n = 24 for SRD part; n = 12 for MD part) entered this Phase I trial. BI 1291583 was safe and well tolerated across the doses tested. All AEs were of mild intensity, with no drug‐related treatment‐emergent AEs, deaths, serious AEs or AEs of special interest reported in either part of the trial. Following both SRD and MD administration, BI 1291583 was readily absorbed, and PK was supraproportional over the doses assessed. Conclusion The results show that BI 1291583 has an appropriate benefit–risk ratio for Japanese patients, with no safety or exposure concerns at the doses studied. Japanese patients with bronchiectasis can be safely integrated into future global clinical trials of BI 1291583, with no dose adjustment required.