TY - JOUR
T1 - Phase 2 clinical trial of PBI-4050 in patients with idiopathic pulmonary fibrosis
AU - Khalil, Nasreen
AU - Manganas, Helene
AU - Ryerson, Christopher J.
AU - Shapera, Shane
AU - Cantin, Andre M.
AU - Hernandez, Paul
AU - Turcotte, Eric E.
AU - Parker, Joseph M.
AU - Moran, John E.
AU - Albert, Gary R.
AU - Sawtell, Renata
AU - Hagerimana, Aline
AU - Laurin, Pierre
AU - Gagnon, Lyne
AU - Cesari, Frank
AU - Kolb, Martin
N1 - Funding Information:
Support statement: This study was funded by Prometic Life Sciences Inc. Funding information for this article has been deposited with the Crossref Funder Registry.
Publisher Copyright:
Copyright ©ERS 2019.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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, 16 patients received PBI-4050 with nintedanib and 16 patients received PBI-4050 with pirfenidone. PBI-4050 alone or in combination with nintedanib or pirfenidone was 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), either in % predicted or mL, from baseline to week 12 for PBI-4050 alone or PBI-4050+nintedanib. In contrast, a statistically significant reduction (p<0.024) in FVC % pred was seen for PBI-4050+pirfenidone after 12 weeks. There were no safety concerns with PBI-4050 alone or 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.
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, 16 patients received PBI-4050 with nintedanib and 16 patients received PBI-4050 with pirfenidone. PBI-4050 alone or in combination with nintedanib or pirfenidone was 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), either in % predicted or mL, from baseline to week 12 for PBI-4050 alone or PBI-4050+nintedanib. In contrast, a statistically significant reduction (p<0.024) in FVC % pred was seen for PBI-4050+pirfenidone after 12 weeks. There were no safety concerns with PBI-4050 alone or 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.
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U2 - 10.1183/13993003.00663-2018
DO - 10.1183/13993003.00663-2018
M3 - Article
C2 - 30578394
AN - SCOPUS:85063291191
SN - 0903-1936
VL - 53
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 3
M1 - 1800663
ER -