Published ahead of print on April 19, 2007, doi:10.1164/rccm.200608-1238OC Am. J. Respir. Crit. Care Med., Volume 176, Number 4, August 2007, 362-369 A more recent version of this article appeared on August 15, 2007
Submitted on August 30, 2006 Phase 2 Randomized Safety and Efficacy Trial of Nebulized Denufosol Tetrasodium in Cystic FibrosisRobin R Deterding1*,1 The Children's Hospital, Denver, CO, USA; University of Colorado, Denver, CO, USA, 2 Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA; Inspire Pharmaceuticals, Inc., Durham, NC, USA, 3 Inspire Pharmaceuticals, Inc., Durham, NC, USA, 4 Cystic Fibrosis Therapeutics Development Network, Seattle, WA, USA, 5 Cincinnati Children's Hospital, Cincinnati, OH, USA; College of Medicine, University of Cincinnati, Cincinnati, OH, USA * To whom correspondence should be addressed. 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-CFTR mechanism in the lung.
Objectives: To examine the safety and efficacy of 28 days of treatment with denufosol compared to placebo in mild cystic fibrosis patients.
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 Key words: clinical trial, lung function, adverse event
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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.
Results: Eighty-nine patients were randomized and received 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 FEV1 (p-value=0.006), FEF25%-75% (p-value=0.008), FVC (p-value=0.022), and FEV1/FVC (p-value=0.047) than placebo patients at the end of the study.
Conclusion: Denufosol administered three times daily for 28 days appeared to be safe and well-tolerated in this mild population and provided preliminary evidence of potential benefit in lung function.
