Denufosol stimulates chloride secretion independent of the chloride channel which is dysfunctional in cystic fibrosis (CF) and therefore has the potential to benefit CF patients regardless of genotype.

To assess the efficacy of denufosol in CF patients with mild lung function impairment age 5years and older.

This multicenter, randomized, parallel group double-blind placebo-controlled trial was conducted at 102 CF care centers in Australia, Canada and the United States (NCT00625612) The active group (n=233) received 60mg denufosol via inhalation three times daily The primary efficacy endpoint was change in FEV₁ in liters from Day 0 to week 48.

685 patients were screened for the study and 466 patients (233 in each group) were randomized to study treatment. The adjusted mean change in FEV₁was 40mL for denufosol and 32mL for placebo with a resulting treatment effect of 8mL (95% CI −0.040, 0.056). The average rate of change in FEV₁ percent of predicted over 0 to 48weeks was −3.04% for placebo vs. −2.30 for denufosol (a difference of 24% relative to placebo) among all patients. The incidence of pulmonary exacerbation was 26% vs. 21% for the placebo and denufosol groups with no differences in the time to first event. The study treatments were well tolerated and there was no evidence of systemic effects in any safety parameter assessed.

In patients with CF treatment with denufosol for 48weeks did not improve pulmonary function or reduce the incidence of pulmonary exacerbations.