RT Journal Article
SR Electronic
T1 Phase 2 clinical trial of PBI-4050 in patients with idiopathic pulmonary fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1800663
DO 10.1183/13993003.00663-2018
A1 Nasreen Khalil
A1 Helene Manganas
A1 Christopher J. Ryerson
A1 Shane Shapera
A1 Andre M. Cantin
A1 Paul Hernandez
A1 Eric E. Turcotte
A1 Joseph M. Parker
A1 John E. Moran
A1 Gary R. Albert
A1 Renata Sawtell
A1 Aline Hagerimana
A1 Pierre Laurin
A1 Lyne Gagnon
A1 Frank Cesari
A1 Martin Kolb
YR 2018
UL http://erj.ersjournals.com/content/early/2018/11/01/13993003.00663-2018.abstract
AB PBI-4050, is a novel orally active small-molecule compound, with demonstrated anti-fibrotic activity in several models of fibrosis, including lung fibrosis. We present results from our first clinical study of PBI-4050 in patients with idiopathic pulmonary fibrosis (IPF).This 12-week open-label study explored the safety, efficacy, and pharmacokinetics of daily oral doses of 800 mg PBI-4050 alone and in combination with nintedanib or pirfenidone in patients with predominantly mild or moderate IPF. Nine patients received PBI-4050 alone and, 16 patients each received PBI-4050/nintedanib and PBI-4050/pirfenidone.PBI-4050 alone or in combination with nintedanib or pirfenidone were well tolerated. Pharmacokinetic profiles for PBI-4050 were similar in the PBI-4050 alone and PBI-4050/nintedanib groups but reduced in the PBI-4050/pirfenidone group, suggesting a drug-drug interaction. There were no significant changes in forced vital capacity (FVC), percent-predicted or mL, from baseline to Week 12 for PBI-4050 alone and PBI-4050/nintedanib. In contract, a statistically significant reduction (p<0.024) in percent-predicted FVC was seen for PBI-4050/pirfenidone after 12 weeks.There were no safety concerns with PBI-4050 alone and in combination with nintedanib or pirfenidone in IPF patients. The stability of FVC between baseline and Week 12 looked encouraging for PBI-4050 alone and in combination with nintedanib.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. 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 ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Khalil has nothing to disclose.Conflict of interest: Dr. Manganas reports other from Prometic, during the conduct of the study.Conflict of interest: Dr. Ryerson reports other from ProMetic, during the conduct of the study; grants and personal fees from Boehringer Ingelheim, grants and personal fees from Hoffmann-La Roche, outside the submitted work.Conflict of interest: Dr. Cantin reports grants from Prometic, personal fees from Prometic, during the conduct of the study.Conflict of interest: Dr. Hernandez reports grants from Prometic, during the conduct of the study; personal fees from Actelion, personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, grants from CSL Behring, grants from Grifols, personal fees from GSK, grants and personal fees from Bayer, personal fees from Novartis, grants from Cyclomedica, personal fees from Teva, personal fees from Trudell, outside the submitted work.Conflict of interest: Dr. Parker reports other from Prometic Lifesciences , during the conduct of the study.Conflict of interest: Dr. Moran reports personal fees and other from Prometic Life Sciences Inc., outside the submitted work.Conflict of interest: Mr. Albert is an employee of Prometic Life Sciences Inc.Conflict of interest: Dr. Hagerimana reports other from Prometic Life Sciences Inc., during the conduct of the study.Conflict of interest: Dr. Laurin reports personal fees and other from Prometic Life Sciences Inc, outside the submitted work; In addition, Dr. Laurin has a patent EP 2427417 issued, a patent EP 2427416 issued, and a patent EP 2970088 pending.Conflict of interest: Dr. Gagnon reports personal fees and other from Prometic Life Sciences Inc, outside the submitted work; In addition, Dr. Gagnon has a patent EP 2427417 issued, a patent EP 2427416 issued, and a patent EP 2970088 pending.Conflict of interest: Dr. Cesari reports personal fees and other from Prometic Life Sciences Inc., outside the submitted work.Conflict of interest: Dr. Kolb reports grants from Prometic , during the conduct of the study; grants and personal fees from Roche, grants and personal fees from Boehringer Ingelheim, grants and personal fees from GSK, personal fees from Gilead, grants from Actelion, grants from Respivert, personal fees from Genoa, grants from Alkermes, grants from Pharmaxis, outside the submitted work.Conflict of interest: Luz Sawtell reports other from Prometic Lifesciences , during the conduct of the study.Conflict of interest: Dr. Turcotte has nothing to disclose.Conflict of interest: Dr. Shane reports personal fees from Astrazeneca, grants, personal fees and other from Boehringer-Ingelheim Canada, grants, personal fees and other from Hoffman La-Roche Canada, other from Medimmune, other from Prometic Canada, other from Sanofi-Aventis, outside the submitted work.