title: Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly impaired lung function.
abstract: BACKGROUND
  Intervention for cystic fibrosis lung disease early in its course has the potential to delay or prevent progressive changes that lead to irreversible airflow obstruction. Denufosol is a novel ion channel regulator designed to correct the ion transport defect and increase the overall mucociliary clearance in cystic fibrosis lung disease by increasing chloride secretion, inhibiting sodium absorption, and increasing ciliary beat frequency in the airway epithelium independently of cystic fibrosis transmembrane conductance regulator genotype.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of denufosol in patients with cystic fibrosis who had normal to mildly impaired lung function characteristic of early cystic fibrosis.
  
  
  METHODS
  A total of 352 patients greater than or equal to 5 years old with cystic fibrosis who had FEV(1) greater than or equal to 75% of predicted normal were randomized to receive inhaled denufosol, 60 mg, or placebo three times daily in a Phase 3, randomized, double-blind, placebo-controlled, 24-week trial.
  
  
  RESULTS
  Main outcome measures included change in FEV(1) from baseline to Week 24 endpoint and adverse events. Mean change from baseline to Week 24 endpoint in FEV(1) (primary efficacy endpoint) was 0.048 L for denufosol (n = 178) and 0.003 L for placebo (n = 174; P = 0.047). No significant differences between groups were observed for secondary endpoints including exacerbation rate and other measures of lung function. Denufosol was well tolerated with adverse event and growth profiles similar to placebo.
  
  
  CONCLUSIONS
  Denufosol improved lung function relative to placebo in cystic fibrosis patients with normal to mildly impaired lung function. Clinical trial registered with www.clinicaltrials.gov (NCT00357279).
authors.affiliation: University of Colorado Denver, 13123 East 16th Avenue, B395, Aurora, CO 80045. accurso.frank@tchden.org.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Accurso
authors.forename: Richard B
authors.initials: RB
authors.lastname: Moss
authors.forename: Robert W
authors.initials: RW
authors.lastname: Wilmott
authors.forename: Ran D
authors.initials: RD
authors.lastname: Anbar
authors.forename: Amy E
authors.initials: AE
authors.lastname: Schaberg
authors.forename: Todd A
authors.initials: TA
authors.lastname: Durham
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D003845:Deoxycytosine Nucleotides / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014529:Uridine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D003845:Deoxycytosine Nucleotides; C465279:denufosol tetrasodium; D014529:Uridine