Published ahead of print on April 19, 2007, doi:10.1164/rccm.200608-1238OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200608-1238OC
Phase 2 Randomized Safety and Efficacy Trial of Nebulized Denufosol Tetrasodium in Cystic Fibrosis1 The Children's Hospital, Denver, Colorado; 2 University of Colorado, Denver, Colorado; 3 University of North Carolina, Department of Biostatistics, Chapel Hill, North Carolina; 4 Inspire Pharmaceuticals, Inc., Durham, North Carolina; 5 Cystic Fibrosis Therapeutics Development Network, Seattle, Washington; 6 Cincinnati Children's Hospital, Cincinnati, Ohio; and 7 University of Cincinnati, College of Medicine, Cincinnati, Ohio Correspondence and requests for reprints should be addressed to Robin Deterding, M.D., The Children's Hospital, 1056 East 19th Avenue, B395, Denver, CO 80218. E-mail: deterding.robin{at}tchden.org Rationale: Denufosol tetrasodium is a selective P2Y2 agonist that enhances mucosal hydration and mucus clearance by activating Cl– secretion and inhibiting epithelial Na+ transport through a non–cystic fibrosis transmembrane conductance regulator mechanism in the lung. Objectives: To examine the safety and efficacy of 28 days of treatment with denufosol compared with placebo in patients with mild cystic fibrosis.
Methods: The study was a randomized, double-blind, multi-center, 28-day, phase 2 clinical trial of denufosol tetrasodium inhalation solution (20, 40, or 60 mg) versus placebo (normal saline). Patients with screening FEV1 Measurements and Main Results: Eighty-nine patients were randomized and received the study drug, 94% completed the study, and 98% were compliant with dosing. All treatments were generally well tolerated, with no dose–response trends observed with respect to safety parameters. The most common adverse event was cough (52% of placebo patients and 47% of denufosol patients). Five patients discontinued early due to adverse events, two on placebo and three on denufosol. Denufosol patients (pooling active doses) had significantly higher changes from baseline in FEV1 (P = 0.006), FEF25%-75% (P = 0.008), FVC (P = 0.022), and FEV1/FVC (P = 0.047) than placebo patients at the end of the study. Conclusions: Denufosol administered three times daily for 28 days appeared to be safe and well tolerated in this population with mild cystic fibrosis and provided preliminary evidence of potential benefit in lung function.
Key Words: clinical trial • lung function • adverse event
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75% of predicted normal value and not treated with inhaled antibiotics for the past 30 days were randomized to receive one of three doses of denufosol or placebo administered three times daily. 
