Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly impaired lung function
American journal of respiratory and critical care medicine, 2011•atsjournals.org
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 …
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 …
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 www.clinicaltrials.gov (NCT00357279).
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