Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD

SummaryBackgroundCombining maintenance medications with different mechanisms of action may improve outcomes in COPD. In this study we evaluated the efficacy and safety of fluticasone/salmeterol (FSC) (250/50 mcg twice daily) when added to tiotropium (18 mcg once daily) (TIO) in subjects with symptomatic moderate to severe COPD.MethodsThis was a 24-week, randomized, double-blind, parallel group, multi-center study. Subjects 40 years or older with cigarette smoking history ≥10 pack-years and with the diagnosis of COPD and post-bronchodilator FEV1 ≥40 to ≤ 80% of predicted normal and FEV1/FVC of ≤0.70 were enrolled. Following a 4-week treatment with open-label TIO 18 mcg once daily, subjects were randomized in a double-blind fashion to either the addition of FSC 250/50 DISKUS twice daily or matching placebo. The primary efficacy endpoint was AM pre-dose FEV1 and secondary endpoints included other measures of lung function, rescue albuterol use, health status and exacerbations.ResultsThe addition of FSC to TIO significantly improved lung function indices including AM pre-dose FEV1, 2 h post-dose FEV1, AM pre-dose FVC, 2 h post-dose FVC and AM pre-dose IC compared with TIO alone. Furthermore, this combination was superior to TIO alone in reducing rescue albuterol use. However, there were no significant differences between the treatment groups in health status or COPD exacerbations. The incidence of adverse events was similar in both groups.ConclusionsThe addition of FSC to subjects with COPD treated with TIO significantly improves lung function without increasing the risk of adverse events. NCT00784550

Lung deposition of inhaled once-daily long-acting muscarinic antagonists standard jet nebulizer or dry powder inhaler, measured using functional respiratory imaging, in patients with chronic obstructive pulmonary disease

Background: Data for bronchodilator deposition via nebulizers and dry powder inhalers (DPIs) in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD) are limited. We used functional respiratory imaging (FRI) to determine deposition patterns for revefenacin solution via a PARI LC ® Sprint ® nebulizer and tiotropium powder via HandiHaler ® DPI. Methods: Ten patients with COPD, of whom 9 had severe airflow obstruction, were selected from FLUIDDA’s database. The study did not enroll patients. Drug deposition in the extrathoracic and intrathoracic regions, including the central and peripheral airways was simulated by FRI. The percentage of delivered dose and central-to-peripheral (C/P) deposition ratio for nebulizer and DPI were evaluated. Results: Mean ± standard deviation (SD) age was 64.7 ± 7.1 years, height was 168.8 ± 8.5 cm, and percent predicted forced expiratory volume in 1 s was 40.8 ± 12.3%; 50% of patients were men. At optimal inhalation flow, intrathoracic and peripheral deposition was three-fold higher for revefenacin via nebulizer than tiotropium via HandiHaler (mean ± SD 34.6 ± 8.53% versus 10.9 ± 5.67% and 18.2 ± 4.30% versus 5.8 ± 2.73% of delivered dose, respectively). Similar results were observed for suboptimal flow (mean ± SD percentage of revefenacin versus tiotropium: intrathoracic, 32.1 ± 8.3% versus 15.1 ± 5.9%; peripheral; 16.6 ± 4.1% versus 8.4 ± 2.9%). The C/P deposition ratio for nebulizer was similar to DPI (mean ± SD 0.915 ± 0.241 versus 0.812 ± 0.249 at optimal; 0.947 ± 0.253 versus 0.784 ± 0.219 at suboptimal flow), even though the mass median aerodynamic diameter of revefenacin was higher than tiotropium. C/P deposition ratio for revefenacin decreased after bronchodilation (0.915 ± 0.241 pre-bronchodilation versus 0.799 ± 0.192 post-bronchodilation), suggesting progressively better deposition in the peripheral region, assuming bronchodilation occurred during the nebulization process. Conclusions: These results demonstrate more efficient intrathoracic and peripheral deposition for revefenacin via standard jet nebulizer than tiotropium via HandiHaler, with similar C/P deposition ratio in patients with COPD. Nebulizers are an efficient alternative to DPIs for bronchodilator administration in patients with COPD

Summary of number of subjects reporting all AEs on treatment.

<p>Note: Total is the total number of subjects experiencing the event not a total number of events.</p><p>UMEC = umeclidinium; VI = vilanterol.</p

Summary of heart rate parameter adjusted means.

<p>Summary of heart rate parameter adjusted means.</p

Summary of QTc adjusted means.

<p>Summary of QTc adjusted means.</p