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J Cyst Fibros. 2014 Mar;13(2):148-55. doi: 10.1016/j.jcf.2013.12.009. Epub 2014 Jan 17.

A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis.

Author information

1
Rainbow Babies & Children's Hospital, Cleveland, OH, USA; Case Western Reserve University, Cleveland, OH, USA. Electronic address: michael.konstan@UHhospitals.org.
2
Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany.
3
Seattle Children's Hospital, Seattle, WA, USA.
4
Research Institute of the McGill University Health Centre, Montreal Children's Hospital, Montreal, QC, Canada.
5
Case Western Reserve University, Cleveland, OH, USA.
6
Boehringer Ingelheim, USA.
7
Boehringer Ingelheim, Germany.
8
Boehringer Ingelheim, Canada.

Abstract

BACKGROUND:

Airway inflammation, mediated in part by LTB4, contributes to lung destruction in patients with cystic fibrosis (CF). LTB(4)-receptor inhibition may reduce airway inflammation. We report the results of a randomized, double-blind, placebo-controlled study of the efficacy and safety of the leukotriene B(4) (LTB(4))-receptor antagonist BIIL 284 BS in CF patients.

METHODS:

CF patients aged ≥6 years with mild to moderate lung disease were randomized to oral BIIL 284 BS or placebo once daily for 24 weeks. Co-primary endpoints were change in FEV(1) and incidence of pulmonary exacerbation.

RESULTS:

After 420 (155 children, 265 adults) of the planned 600 patients were randomized, the trial was terminated after a planned interim analysis revealed a significant increase in pulmonary related serious adverse events (SAEs) in adults receiving BIIL 284 BS. Final analysis revealed SAEs in 36.1% of adults receiving BIIL 284 BS vs. 21.2% receiving placebo (p = 0.007), and in 29.6% of children receiving BIIL 284 BS vs. 22.9% receiving placebo (p = 0.348). In adults, the incidence of protocol-defined pulmonary exacerbation was greater in those receiving BIIL 284 BS than in those receiving placebo (33.1% vs. 18.2% respectively; p = 0.005). In children, the incidence of protocol-defined pulmonary exacerbation was 19.8% in the BIIL 284 BS arm, and 25.7% in the placebo arm (p = 0.38).

CONCLUSIONS:

While the cause of increased SAEs and exacerbations due to BIIL 284 BS is unknown, the outcome of this trial provides a cautionary tale for the administration of potent anti-inflammatory compounds to individuals with chronic infections, as the potential to significantly suppress the inflammatory response may increase the risk of infection-related adverse events.

KEYWORDS:

Anti-inflammatory therapy; Clinical trial; Cystic fibrosis; Leukotriene B(4) receptor antagonist; Lung disease

Comment in

PMID:
24440167
PMCID:
PMC4755340
DOI:
10.1016/j.jcf.2013.12.009
[Indexed for MEDLINE]
Free PMC Article

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