TY - JOUR T1 - Phase I studies of BI 1015550, a preferential phosphodiesterase 4B inhibitor, in healthy males and patients with idiopathic pulmonary fibrosis JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00240-2022 VL - 8 IS - 4 SP - 00240-2022 AU - Toby M. Maher AU - Christina Schlecker AU - Doreen Luedtke AU - Sebastian Bossert AU - Donald F. Zoz AU - Armin Schultz Y1 - 2022/10/01 UR - http://openres.ersjournals.com/content/8/4/00240-2022.abstract N2 - 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 male subjects 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 male subjects 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 male subjects and male and female patients with IPF, supporting further development in larger trials.A preferential PDE4B inhibitor, BI 1015550, is a candidate drug for the treatment of fibrotic interstitial lung disease. In Phase I studies, BI 1015550 had an acceptable safety profile in healthy males and patients with idiopathic pulmonary fibrosis. https://bit.ly/3zSOtLs ER -