Phase 2 Randomized Safety and Efficacy Trial of Nebulized Denufosol Tetrasodium in Cystic Fibrosis

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 ⩾ 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.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 w...