PMID- 36299369
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221028
IS  - 2312-0541 (Print)
IS  - 2312-0541 (Electronic)
IS  - 2312-0541 (Linking)
VI  - 8
IP  - 4
DP  - 2022 Oct
TI  - Phase I studies of BI 1015550, a preferential phosphodiesterase 4B inhibitor, in 
      healthy males and patients with idiopathic pulmonary fibrosis.
LID - 00240-2022 [pii]
LID - 10.1183/23120541.00240-2022 [doi]
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 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.
CI  - Copyright (c)The authors 2022.
FAU - Maher, Toby M
AU  - Maher TM
AD  - Inflammation, Repair, and Development Section, National Heart and Lung Institute, 
      Imperial College London, London, UK.
AD  - Keck Medicine of USC, Los Angeles, CA, USA.
FAU - Schlecker, Christina
AU  - Schlecker C
AD  - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.
FAU - Luedtke, Doreen
AU  - Luedtke D
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
FAU - Bossert, Sebastian
AU  - Bossert S
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
FAU - Zoz, Donald F
AU  - Zoz DF
AD  - Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA.
FAU - Schultz, Armin
AU  - Schultz A
AD  - CRS Clinical Research Services Mannheim GmbH, Mannheim, Germany.
LA  - eng
PT  - Journal Article
DEP - 20221024
PL  - England
TA  - ERJ Open Res
JT  - ERJ open research
JID - 101671641
PMC - PMC9589333
COIS- Conflict of interest: T.M. Maher has received consultancy fees from Boehringer 
      Ingelheim, Roche/Genentech, AstraZeneca, Bayer, Blade Therapeutics, Bristol-Myers 
      Squibb, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Pliant, Respivant, Theravance 
      and Veracyte; and honoraria from Boehringer Ingelheim and Roche/Genentech. C. 
      Schlecker, D. Leudtke, S. Bossert and D.F. Zoz are employees of Boehringer 
      Ingelheim. A. Schultz is an employee of CRS Clinical Research Services Mannheim 
      GmbH.
EDAT- 2022/10/28 06:00
MHDA- 2022/10/28 06:01
PMCR- 2022/10/24
CRDT- 2022/10/27 02:22
PHST- 2022/05/16 00:00 [received]
PHST- 2022/06/10 00:00 [accepted]
PHST- 2022/10/27 02:22 [entrez]
PHST- 2022/10/28 06:00 [pubmed]
PHST- 2022/10/28 06:01 [medline]
PHST- 2022/10/24 00:00 [pmc-release]
AID - 00240-2022 [pii]
AID - 10.1183/23120541.00240-2022 [doi]
PST - epublish
SO  - ERJ Open Res. 2022 Oct 24;8(4):00240-2022. doi: 10.1183/23120541.00240-2022. 
      eCollection 2022 Oct.