Denufosol Tetrasodium in Patients with Cystic Fibrosis and Normal to Mildly Impaired Lung Function

Frank J. Accurso, Richard B. Moss, Robert W. Wilmott, Ran D. Anbar, Amy E. Schaberg, Todd A. Durham, Bonnie W. Ramsey, R. Ahrens, R. Anbar, D. Lindner, P. Anderson, A. Atlas, Y. Berthiaume, N. Beaudoin, D. Bisberg, P. Pock, S. Boas, D. Borowitz, J. Smith, A. S. ChidekelB. Chipps, J. F. Chmiel, B. Ksenich, J. P. Clancy, J. Colombo, D. Heimes, C. Daines, J. DeCelie-Germana, S. Galvin, R. Deterding, E. DiMango, H. Dorkin, A. Dozor, I. Gherson, J. Dunitz, M. Egan, J. Young, G. Elliott, J. Gadd, P. Fornos, M. Franco, D. Froh, R. Kelly, D. Geller, D. Cook, R. Gibson, A. Genatossio, G. Gong, G. Graff, K. Hardy, A. Robles, D. Hicks, M. Howenstine, L. Bendy, K. Jones, A. Gardner, J. Kanga, B. Owsley, J. Kreindler, C. Lapin, G. Drapeau, R. Lee, M. Dillard, T. Liou, K. S. McCoy, P. Olson, S. Millard, R. Moss, C. Dunn, Z. Davies, C. Nakamura, T. Brascia, S. Nasr, C. Oermann, L. Traplena, C. Prestidge, A. Prestridge, D. Delute, C. Ren, G. Retsch-Bogart, D. Towle, C. Barlow, S. Reyes, D. Roberts, V. Roberts, M. Rock, L. Makholm, R. Rubenstein, C. Kubrak, C. Murray, D. Schaeffer, E. DeLuca, M. Schechter, J. Peabody, D. Schellhase, P. Walker, C. Grece, M. Wall, A. Guzik, D. Weiner, A. Horn, D. B. Willey-Courand, V. Kociela, M. Woo, J. Wooldridge, L. Duan, P. Zeitlin, J. Zuckerman, R. Kennedy-DuDevoir

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Rationale: 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. Objectives: 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 FEV1 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. Measurements and Main Results: Main outcome measures included change in FEV1 from baseline to Week 24 endpoint and adverse events. Mean change from baseline to Week 24 endpoint in FEV1 (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 (NCT00357279).

Original languageEnglish (US)
Pages (from-to)627-634
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Issue number5
StatePublished - Mar 1 2011


  • Chloride channel activator
  • ENaC inhibition
  • Early intervention
  • Ion channel regulator
  • P2y receptor agonist

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Pulmonary and Respiratory Medicine


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