Long term effects of denufosol tetrasodium in patients with cystic fibrosis

RationaleDenufosol 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.ObjectivesTo assess the efficacy of denufosol in CF patients with mild lung function impairment age 5 years and older.MethodsThis 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 60 mg denufosol via inhalation three times daily The primary efficacy endpoint was change in FEV1 in liters from Day 0 to week 48.Measurements and main results685 patients were screened for the study and 466 patients (233 in each group) were randomized to study treatment. The adjusted mean change in FEV1was 40 mL for denufosol and 32 mL for placebo with a resulting treatment effect of 8 mL (95% CI − 0.040, 0.056). The average rate of change in FEV1 percent of predicted over 0 to 48 weeks 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.ConclusionsIn patients with CF treatment with denufosol for 48 weeks did not improve pulmonary function or reduce the incidence of pulmonary exacerbations.