RT Journal Article SR Electronic T1 Phase I studies of BI 1015550, a preferential PDE4B inhibitor, in healthy males and patients with idiopathic pulmonary fibrosis JF ERJ Open Research JO erjor FD European Respiratory Society SP 00240-2022 DO 10.1183/23120541.00240-2022 A1 Toby M. Maher A1 Christina Schlecker A1 Doreen Luedtke A1 Sebastian Bossert A1 Donald F. Zoz A1 Armin Schultz YR 2022 UL http://openres.ersjournals.com/content/early/2022/06/16/23120541.00240-2022.abstract AB Introduction BI 1015550 is a phosphodiesterase 4 (PDE4) inhibitor that has antifibrotic properties. Phase I and Ic studies were conducted to investigate the safety, tolerability and pharmacokinetics of BI 1015550 in healthy males and patients with idiopathic pulmonary fibrosis (IPF).Methods In the Phase I study, 42 subjects were partially randomised to receive placebo or BI 1015550 in single rising doses of 36 mg and 48 mg, or multiple rising doses of 6 mg and 12 mg twice daily over 14 days. In the Phase Ic study, 15 patients with IPF were randomised to receive 18 mg BI 1015550 or placebo twice daily for up to 12 weeks. For both studies, the primary endpoint was the number of subjects with drug-related adverse events (AEs).Results In the Phase I study, drug-related AEs were reported for 50.0% of healthy males treated with a single dose of BI 1015550, compared with 16.7% receiving placebo. For those receiving multiple doses, drug-related AEs were reported for 37.5% of those treated with BI 1015550 and 12.5% receiving placebo. The most frequently reported AEs by organ class were nervous system disorders, which were largely driven by headache. In the Phase Ic study, drug-related AEs were reported in 90.0% of patients treated with BI 1015550, compared with 60.0% of those receiving placebo. The most frequent AEs by organ class were gastrointestinal AEs.Conclusions BI 1015550 had an acceptable safety profile in healthy males and patients with IPF, supporting further development in larger trials.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.