Abstract
Background: Neutrophil elastase (NE) is increased in COPD sputum and bronchoalveolar lavage fluid and correlates with clinical symptoms. NE inhibition (NEi) may reduce tissue damage and inflammation.
Methods: We conducted two Phase I trials: NCT03588390 (single-blind, partially randomised, placebo-controlled, parallel-group) and NCT03802331 (open-label, randomised, single-dose, two-way crossover); in subjects aged 18–45 receiving BI 1323495 orally, as single rising doses of 10‒600mg (NCT03588390) or two single 100mg doses (NCT03802331). Primary endpoints were number of subjects with investigator-defined drug-related adverse events (DRAEs) (NCT03588390), AUC0–tz and Cmax (NCT03802331).
Results: 63 subjects entered NCT03588390; 12 entered NCT03802331. DRAEs were reported in 12 (NCT03588390) and 1 (NCT03802331) subjects; all were mild or moderate and resolved by trial end. Headache was the most common DRAE in subjects receiving BI 1323495 (6 subjects in NCT03588390 and 1 in NCT03802331). NCT03588390 established a pharmacokinetic/pharmacodynamic relationship. A drug concentration of ~70nmol/L achieved 95% NEi in zymosan-stimulated blood. A linear relationship between dose and exposure was demonstrated by a power model in doses ≤300mg (Figure); exposure was higher when administered with food.
Conclusions: BI 1323495 was well tolerated in doses up to 600mg, with dose linearity up to 300mg. Exposure was higher in fed than fasted state.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3296.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020
