Once-daily ciclesonide 80 or 320μg for 12 weeks is safe and effective in patients with persistent asthma

SummaryThe efficacy and safety of ciclesonide was assessed in this randomized, placebo-controlled study in patients with persistent asthma (randomized n=360) maintained on low to moderate doses of inhaled corticosteroids. Patients were randomized to receive ciclesonide 80 or 320μg (ex-actuator doses, equivalent to 100 and 400μg ex-valve, respectively) or placebo once daily in the morning via metered-dose inhaler for 12 weeks. Morning peak expiratory flow was maintained throughout the treatment period in patients treated with ciclesonide and decreased significantly in patients treated with placebo (P=0.0003). Ciclesonide (80 and 320μg) significantly increased forced expiratory volume in 1s from baseline (0.13 and 0.19L increases, respectively; P<0.01); improvements were superior versus placebo (P=0.0044 for 80μg ciclesonide; P<0.0001 for 320μg ciclesonide). The probability of losing efficacy decreased in a dose-dependent manner (55% for placebo, 38% for ciclesonide 80μg, 23% for ciclesonide 320μg). Asthma symptom scores and rescue medication use were unchanged with ciclesonide and significantly worsened with placebo. The incidence of adverse events was comparable in all treatment groups and no cortisol suppression was observed. Therefore, ciclesonide 80 and 320μg administered once daily was a safe and effective maintenance treatment for patients with persistent asthma

Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial

Kai M Beeh,1 Dave Singh,2 Lilla Di Scala,3 Anton Drollmann31insaf Respiratory Research Institute, Wiesbaden, Germany; 2University Of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester, Manchester, UK; 3Novartis Pharma AG, Basel, SwitzerlandIntroduction: Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD). We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.Methods: Patients were randomized to a cross-over design of once-daily NVA237 50 &amp;micro;g or placebo for 3 weeks, with a 14-day washout. Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment. The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.Results: A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted). Ninety-five patients completed the study. On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P &amp;lt; 0.001); the effect was also significant from Day 1, with an increase of 10%. Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study. This was accompanied by inverse decreases in residual volume and functional residual capacity. NVA237 was superior to placebo (P &amp;lt; 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime). The safety profile of NVA237 was similar to that of the placebo.Conclusion: NVA237 50 &amp;micro;g once daily produced immediate and significant improvement in exercise tolerance from Day 1. This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea. Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance. (ClinicalTrials.gov Identifier: NCT01154127).Keywords: COPD, dyspnea, FEV1, exercise tolerance, LAMA, NVA23

Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma

SummaryBackgroundThe aim of this study was to compare the efficacy and safety of once-daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma.MethodsEligible patients requiring budesonide or equivalent 320–640μg (ex-mouthpiece, equivalent to 400–800μg; Turbohaler™) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280μg/day; ex-mouthpiece, equivalent to 1600μg/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of ⩾7% or ⩾0.15L were randomised to ciclesonide 320μg (ex-actuator, equivalent to 400μg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320μg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint.ResultsIn all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P=0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P=0.017). Rescue medication use decreased significantly only for ciclesonide patients (P=0.009). Frequency of adverse events was low in both groups.ConclusionCiclesonide 320μg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320μg once daily in persistent asthma