on behalf of the INTENSITY study investigators ABSTRACT: Two, once daily (q.d.) inhaled bronchodilators are available for the treatment of chronic obstructive pulmonary disease (COPD): the b 2 -agonist indacaterol and the anticholinergic tiotropium. This blinded study compared the efficacy of these two agents and assessed their safety and tolerability.Patients with moderate-to-severe COPD were randomised to treatment with indacaterol 150 mg q.d. (n5797) or tiotropium 18 mg q.d. (n5801) for 12 weeks.After 12 weeks, the two treatments had similar overall effects on ''trough'' (24 h post-dose) forced expiratory volume in 1 s. Indacaterol-treated patients had greater improvements in transition dyspnoea index (TDI) total score (least squares means 2.01 versus 1.43; p,0.001) and St George's Respiratory Questionnaire (SGRQ) total score (least squares means 37.1 versus 39.2; p,0.001; raw mean change from baseline -5.1 versus -3.0), and were significantly more likely to achieve clinically relevant improvements in these end-points (indacaterol versus tiotropium odds ratios of 1.49 for TDI and 1.43 for SGRQ, both p,0.001). Adverse events were recorded for 39.7% and 37.2% of patients in the indacaterol and tiotropium treatment groups, respectively. The most frequent adverse events were COPD worsening, cough and nasopharyngitis.Both bronchodilators demonstrated spirometric efficacy. The two treatments were well tolerated with similar adverse event profiles. Compared with tiotropium, indacaterol provided significantly greater improvements in clinical outcomes.
Nebulized solutions of long-acting bronchodilators provide an alternative to DPI and MDI delivery, particularly for COPD patients unable to use hand-held devices easily or correctly. The long-acting beta2-agonist, formoterol fumarate, is differentiated by its onset of significant bronchodilation within 5 min of administration. In a randomized, double-blind, double-dummy trial, COPD subjects (n=351, mean forced expiratory volume FEV1=1.3 L, 44% predicted) received nebulized formoterol fumarate (Perforomist inhalation solution; FFIS 20 microg) or DPI (Foradil Aerolizer; FA 12 microg), or placebo twice daily for 12 weeks. Efficacy was assessed with 12-h pulmonary function tests, and quality of life was assessed before and after treatment with the St. George's Respiratory Questionnaire (SGRQ). At the 12-week endpoint, FFIS significantly increased FEV1 AUC0-12h relative to placebo (p<0.0001). No evidence of tachyphylaxis was observed as indicated by maintained FEV1 AUC and reduced rescue albuterol use throughout treatment. FFIS also significantly increased peak FEV1, trough FEV1, and standardized FVC AUC0-12h compared with placebo. SGRQ assessment at Week 12 demonstrated significant and clinically meaningful improvements in total score (FFIS vs placebo, -4.9, p=0.0067), symptom, and impact scores. No significant differences in efficacy were observed between the two active treatments. Drug related AEs in the FFIS arm with a frequency > or = 1% and exceeding placebo were dry mouth, nausea, and insomnia. Nebulized FFIS provided significant improvement in respiratory status and quality of life in subjects with COPD relative to placebo and was well tolerated. The efficacy and safety profile of FFIS was comparable to FA DPI.
BackgroundIpratropium bromide/albuterol Respimat inhaler (CVT-R) was developed as an environmentally friendly alternative to ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI), which uses a chlorofluorocarbon propellant.ObjectiveThe objective of this study was to evaluate patient satisfaction, device usage, and long-term safety of CVT-R compared to CVT-MDI, and to the simultaneous administration of ipratropium bromide hydrofluoroalkane (HFA; I) and albuterol HFA (A) metered-dose inhalers as dual monotherapies (I + A).DesignThis is a 48-week, open-label, randomized, active-controlled, parallel-group study (n = 470) comparing CVT-R to CVT-MDI and to I + A.ParticipantsPatients were at least 40 years of age, diagnosed with chronic obstructive pulmonary disease (COPD), and current or exsmokers.InterventionsPatients were randomized to receive: (1) CVT-R, one inhalation four times daily (QID); or (2) CVT-MDI, two inhalations QID; or (3) I + A two inhalations of each inhaler QID.Main measuresPatient Satisfaction and Preference Questionnaire (PASAPQ) performance score (primary endpoint) and adverse events.Key resultsPASAPQ performance score was significantly higher (CVT-R versus CVT-MDI, 9.6; and CVT-R versus I + A, 6.2; both P < 0.001) when using CVT-R compared to CVT-MDI or I + A at all visits starting from week 3, while CVT-MDI and I + A treatment groups were similar. Time to first COPD exacerbation was slightly longer in the CVT-R group compared to the other treatment groups, although it did not reach statistical significance (CVT-R versus CVT-MDI, P = 0.57; CVT-R versus I + A, P = 0.22). Rates of withdrawal and patient refusal to continue treatment were lower in CVT-R compared with CVT-MDI and I + A groups (CVT-R versus CVT-MDI, P = 0.09; CVT-R versus I + A, P = 0.005). The percentage of patients reporting adverse events and serious adverse events was similar across all three treatment groups.ConclusionCVT-R is an effective, environmentally friendly inhaler that provides patients with a high level of user satisfaction and may positively impact clinical outcomes while having no adverse impacts on patients using the device.
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.
Rationale:COPD Guidelines indicate benefit in combining bronchodilators of different classes. Currently only short-acting combinations are available. Pearl Therapeutics GFF-MDI is an inhaled bronchodilator comprised of glycopyrrolate (GP), a long-acting muscarinic antagonist (LAMA) and formoterol fumarate (FF), an established, long-acting beta-2 agonist (LABA), delivered via a HFA MDI. Pearl's proprietary porous particle technology allows the formulation of FF, GP and the combination thereof in MDI format, with highly stable, robust and aerodynamically efficient drug delivery. Single-dose, Phase 2 data have been reported on the individual agents, as well as Phase 1 pharmacokinetic and safety data for the combination. Based on these findings, Pearl evaluated GFF-MDI in a chronic-dosing study. Methods: To ensure maximum power for key assessments, a randomized, double-blind, customized, unbalanced, incomplete block, crossover study was conducted in patients with moderate to very severe COPD. Two doses of GFF-MDI (72/9.6 and 36/9.6 µg) were compared to GP-MDI 36 µg, FF-MDI 9.6 µg, FF-MDI 7.2 µg, tiotropium DPI 18 µg, formoterol DPI 12 µg and placebo MDI. All actives and placebo were administered twice daily for 1-week, except tiotropium, which was administered once daily for 1-week. The primary efficacy endpoint was change in FEV AUC on Day 7 relative to pre-dose baseline at the start of treatment. Secondary endpoints included Peak FEV , 1 0-12 1 morning trough FEV and safety assessments.1 Results: 118 Patients were randomized into the study. GFF-MDI 72/9.6 µg was superior to GP-MDI 36 µg (109 mL), FF-MDI 9.6 µg (116 mL), FF-MDI 7.2 µg (124 mL), tiotropium DPI (103 mL), formoterol DPI (101 mL) and placebo MDI (298 mL) for the primary endpoint (P <0.0001 for all comparisons). GFF-MDI 36/9.6 µg was non-inferior to GFF-MDI72/9.6 µg (difference = -8 mL; 95% CI: -54;+39 ml; P <0.0001) and superior to all other comparators (P ≤0.0002). Both doses of GFF-MDI were superior to comparators for the secondary endpoints. In addition, GFF-MDI was shown to be safe and well tolerated. The most frequently reported AE was dry mouth, incidence comparable to tiotropium. Conclusion: GFF-MDI is the first fixed dose LAMA/LABA combination bronchodilator to demonstrate superiority to both its components and to tiotropium DPI, and formoterol DPI. There were no clinically relevant or statistically significant differences between the two doses of GFF-MDI. The significant improvement in lung function and overall safety profile observed with GFF-MDI in this trial supports the further advancement of this combination product for the treatment of patients with COPD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.