Phase I Studies of Acebilustat: Biomarker Response and Safety in Patients with Cystic Fibrosis.
There is a significant unmet need for safe and effective anti-inflammatory treatment for cystic fibrosis. The aim of this study was to evaluate the safety of acebilustat, a leukotriene A4 hydrolase inhibitor, and its effect on inflammation biomarkers in patients with cystic fibrosis. Seventeen patients with mild to moderate cystic fibrosis were enrolled and randomized into groups receiving placebo or doses of 50 mg or 100 mg acebilustat administered orally, once daily for 15 days. Sputum neutrophil counts were reduced by 65% over baseline values in patients treated with 100 mg acebilustat. A modestly significant 58% reduction vs. placebo in sputum elastase was observed with acebilustat treatment. Favorable trends were observed for reduction of serum C-reactive protein and sputum neutrophil DNA in acebilustat-treated patients. No changes in pulmonary function were observed. Acebilustat was safe and well tolerated. The results of this study support further clinical development of acebilustat for treatment of cystic fibrosis.
Centre for Infection and Immunity, Dentistry, and Biomedical Sciences, Queens University School of Medicine, Belfast, UK.
J S
JS
Elborn
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
A
A
Horsley
West of Scotland CF Centre, Gartnavel General Hospital, Glasgow, UK.
G
G
MacGregor
Department of Respiratory Medicine, Royal Brompton Hospital, London, UK.
D
D
Bilton
Celtaxsys, Inc, Atlanta, Georgia, USA.
R
R
Grosswald
Celtaxsys, Inc, Atlanta, Georgia, USA.
S
S
Ahuja
Celtaxsys, Inc, Atlanta, Georgia, USA.
E B
EB
Springman
D000328:Adult; D053961:Azabicyclo Compounds / Q000009:adverse effects* / Q000627:therapeutic use*; D001565:Benzoates / Q000009:adverse effects* / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism*; D015169:Colony Count, Microbial; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000503:physiopathology; D008297:Male; D010196:Pancreatic Elastase / Q000378:metabolism; D012129:Respiratory Function Tests; D013183:Sputum / Q000378:metabolism / Q000382:microbiology; D055815:Young Adult
D053961:Azabicyclo Compounds; D001565:Benzoates; D015415:Biomarkers; C000625351:acebilustat; D004247:DNA; D010196:Pancreatic Elastase