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1 CF-Outpatient Clinic, Albert-Ludwigs University, Freiburg, Germany. 2 Service de Pneumologie, Dépt de Mucoviscidose, Erasmus University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium. 3 Kinderpneumologie, Academic Hospital, Vrije Universiteit Brussel (VLB), Brussels, Belgium. 4 Laboratoires SMB & Galephar, Brussels, Belgium. 5 Pulmonary Research Group, University of Alberta, Edmonton, Canada
CORRESPONDENCE: M. King, 173 HMRC, University of Alberta, Edmonton, AB, T6G 2S2, Canada. Fax: 1 7804924878. E-mail: malcolm.king@ualberta.ca
Keywords: airway clearance, cystic fibrosis, epithelial ion transport, mucolytic therapy, protease inhibitors, sputum rheology
Received: March 16, 2001
Accepted September 19, 2001
This study was supported by SMB & Galephar, and in part by the Canadian CF Foundation.
The aim of the present studies was to investigate the tolerability and activity of a novel mucolytic drug, Nacystelyn (NAL), for the treatment of cystic fibrosis (CF) lung disease.
In study 1, involving 10 CF patients, the main objective was to determine the tolerability and potential efficacy of a range of single doses of NAL in comparison to a placebo, in order to establish an optimal dose for further testing. On five consecutive scheduled treatment days, patients inhaled either from two (4 mg) to eight puffs (16 mg) of a single dose of NAL from the range, administered in an open-label fashion, or 12 puffs of active NAL (24 mg) versus 12 puffs of placebo, administered in a randomized double-blind fashion. Pulmonary function data were unaffected and clinically-adverse effects were limited to wheezing in some patients that inhaled 12 puffs of either placebo or active drug. Subsequent rheological analysis of their sputum showed a dose-dependent decrease in sputum viscoelasticity, accompanied by a decrease in sputum solids content and an increase in chloride and sodium concentrations.
In study 2, involving 12 CF patients, the clinical safety and mucolytic activity of a single dose of NAL was monitored over 24 h. On different scheduled treatment days, 7 days apart, patients inhaled a single dose of 12 puffs of active NAL (24 mg) or 12 puffs of placebo drug in a randomized, double-blind sequence, with sputum samples taken at intervals before and after inhalation. Mucus rigidity decreased following NAL inhalation, with the maximum effect observed at 4 h; the 1-, 2- and 4-h NAL rheology results were significantly different from placebo. No adverse effects were observed.
The drug was well tolerated in both studies. Sputum results were predictive of improved clearability by ciliary and cough transport mechanisms.
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