36 research outputs found
Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma
No full textBackground: The 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. Methods: Eligible patients requiring budesonide or equivalent 320-640 mu g (ex-mouthpiece, equivalent to 400-800 mu g; Turbohaler (TM)) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280 mu g/day; ex-mouthpiece, equivalent to 1600 mu g/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of >= 7% or >= 0.15 L were randomised to ciclesonide 320 mu g (ex-actuator, equivalent to 400 mu g ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 mu g once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint. Results: In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12 L, respectively, in the ciclesonide group, and by 0.23 and 0.21 L 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. Conclusion: Ciclesonide 320 mu g once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 mu g once daily in persistent asthma
Bronchodilatory effects of NVA237, a once daily long-acting muscarinic antagonist, in COPD patients
No full textSummaryNVA237 is a novel, once daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This study aimed to assess the 24-h bronchodilatory effect following 14 days of treatment with inhaled NVA237 in patients with mild, moderate or severe COPD.This was a randomized, double-blind, placebo-controlled, two-period, crossover, multicenter study. A total of 33 patients (≥40 years; smoking history of ≥10 pack-years) were randomized to receive NVA237 50 μg once daily followed by placebo or placebo followed by NVA237 50 μg for 14 days. Treatment periods were separated by a 7–14 day washout period. The primary variable was the mean forced expiratory volume in 1 s (FEV1) derived from the area under the curve (AUC) between 0 and 24 h post-dose on Day 14.The 24-h FEV1 profiles showed a consistent bronchodilator effect for NVA237 versus placebo on Day 14. Least square (LS) mean difference in FEV1 AUC0–24 h values between NVA237 and placebo was 163 mL (P < 0.001). There were significant increases in mean FEV1 AUC0–12 h (LS mean difference 165 mL, P = 0.001) and FEV1 AUC12–24 h (161 mL, P < 0.001) versus placebo. NVA237 significantly improved peak FEV1 (by 208 mL, P < 0.001) and trough FEV1 (by 154 mL, P = 0.003) versus placebo on Day 14. NVA237 was well tolerated; all adverse events were mild or moderate in intensity and not related to study drug.NVA237 50 μg once daily was well tolerated and showed significant and sustained 24-h bronchodilation in patients with COPD
Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial
No full textKai 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 &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 &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 &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 &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
Once-daily ciclesonide 80 or 320μg for 12 weeks is safe and effective in patients with persistent asthma
No full textSummaryThe 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
Effect of indacaterol on dynamic lung hyperinflation and breathlessness in patients with COPD
No full textAbstract
Indacaterol is a novel, inhaled once-daily ultra long-acting β2-agonist for the treatment of COPD. This randomised, double-blind, placebo-controlled, two-period crossover study evaluated the effect of two-week treatment with indacaterol 300 μg on peak- and isotime exercise inspiratory capacity (IC) in patients with COPD. Patients (40–80 years) with post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) 120% of predicted normal were randomised to receive indacaterol 300 μg or placebo once-daily via a single-dose dry powder inhaler. Following 14 days of treatment, IC at peak- and isotime during constant-load (80% of maximum workload) cycle ergometry was analysed using linear mixed-effects models. Safety and tolerability were also monitored.
Twenty-seven patients (67% male; mean age, 61.3 years) were randomised; 24 completed the study. On Day 14, indacaterol showed statistically significant improvements over placebo in peak (317 [95% CI: 118–517]; p=0.0033) and isotime IC (268 mL [95% CI: 104–432]; p=0.0026). Statistically significant improvements were observed with indacaterol versus placebo on Day 14 for the following secondary endpoints: resting IC, FEV1, dyspnoea (BDI/TDI and Borg CR10 scale) and exercise endurance time. Indacaterol was well tolerated, with no serious adverse events or deaths.
In conclusion, indacaterol 300 μg administered once-daily showed a clinically relevant increase in IC after 14 days of treatment, reflecting a reduction in dynamic hyperinflation
A Randomized, Double-blind, Placebo-controlled, Multi-center, Two-period Crossover Study To Investigate The Bronchodilatory Effect Of NVA237 50µg Inhaled Once Daily In Patients With COPD
No full textEfficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses
No full textBackground Omalizumab is an established anti-IgE therapy for the treatment of allergic diseases that prevents IgE from binding to its receptor. QGE031 is an investigational anti-IgE antibody that binds IgE with higher affinity than omalizumab. Objective This study compared the effects of QGE031 with those of omalizumab on clinical efficacy, IgE levels, and FcεRI expression in a clinical model of allergic asthma. Methods Thirty-seven patients with mild allergic asthma were randomized to subcutaneous omalizumab, placebo, or QGE031 at 24, 72, or 240 mg every 2 weeks for 10 weeks in a double-blind, parallel-group multicenter study. Inhaled allergen challenges and skin tests were conducted before dosing and at weeks 6, 12, and 18, and blood was collected until 24 weeks after the first dose. Results QGE031 elicited a concentration- and time-dependent change in the provocative concentration of allergen causing a 15% decrease in FEV1 (allergen PC15) that was maximal and approximately 3-fold greater than that of omalizumab (P = .10) and 16-fold greater than that of placebo (P = .0001) at week 12 in the 240-mg cohort. Skin responses reached 85% suppression at week 12 in the 240-mg cohort and were maximal at week 18. The top doses of QGE031 consistently suppressed skin test responses among subjects but had a variable effect on allergen PC15 (2-fold to 500-fold change). QGE031 was well tolerated. Conclusion QGE031 has greater efficacy than omalizumab on inhaled and skin allergen responses in patients with mild allergic asthma. These data support the clinical development of QGE031 as a treatment of asthma
