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1.
Article in English | MEDLINE | ID: mdl-24596459

ABSTRACT

BACKGROUND: Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy. GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting ß2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD. MATERIALS AND METHODS: In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 µg and GLY 50 µg daily (IND + GLY) or IND 150 µg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices). The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12. Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks. RESULTS: A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study. On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001). IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01). TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05). The incidence of adverse events was similar for the two treatment groups. CONCLUSION: In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes.


Subject(s)
Adrenergic beta-2 Receptor Agonists/administration & dosage , Bronchodilator Agents/administration & dosage , Glycopyrrolate/administration & dosage , Indans/administration & dosage , Lung/drug effects , Muscarinic Antagonists/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinolones/administration & dosage , Administration, Inhalation , Adrenergic beta-2 Receptor Agonists/adverse effects , Aged , Area Under Curve , Bronchodilator Agents/adverse effects , Double-Blind Method , Drug Administration Schedule , Drug Therapy, Combination , Europe , Female , Forced Expiratory Volume , Glycopyrrolate/adverse effects , Humans , Indans/adverse effects , Inspiratory Capacity , Lung/physiopathology , Male , Middle Aged , Muscarinic Antagonists/adverse effects , Nebulizers and Vaporizers , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Quinolones/adverse effects , Severity of Illness Index , Time Factors , Treatment Outcome , Vital Capacity
2.
Pulm Pharmacol Ther ; 26(3): 348-55, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23434446

ABSTRACT

BACKGROUND: Guidelines for chronic obstructive pulmonary disease (COPD) recommend that treatment choices be based partly on symptoms. METHODS: A post-hoc analysis of pooled data from clinical studies compared the efficacy and safety of once-daily inhaled bronchodilators indacaterol (150 and 300 µg) and open-label tiotropium (18 µg) according to baseline dyspnoea severity on the modified Medical Research Council (mMRC) scale in patients with COPD (mMRC scores <2 = 'less dyspnoea'; scores ≥2 = 'more dyspnoea'). Outcomes were assessed after 26 weeks. RESULTS: The analysis included 3177 patients. In patients with less dyspnoea: indacaterol (both doses) improved 24-h post-dose ('trough') forced expiratory volume in 1 s (FEV1), transition dyspnoea index (TDI) and St George's Respiratory Questionnaire (SGRQ) total scores at week 26 and reduced the risk of COPD exacerbations vs placebo; and open-label tiotropium improved trough FEV1 and TDI total score vs placebo at week 26. In patients with more dyspnoea: indacaterol (both doses) improved trough FEV1, TDI and SGRQ total scores at week 26; indacaterol 300 µg was the only treatment to improve the TDI total score by more than the minimum clinically important difference (≥1 point) vs placebo; and open-label tiotropium improved trough FEV1, TDI total score at week 26 and decreased the risk of COPD exacerbations vs placebo. In both subgroups, all treatments were well tolerated. CONCLUSIONS: In patients with less dyspnoea, all treatments had similar effects. Indacaterol 300 µg may be a useful treatment option for patients with COPD who experience more severe breathlessness.


Subject(s)
Bronchodilator Agents/therapeutic use , Indans/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinolones/therapeutic use , Scopolamine Derivatives/therapeutic use , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Delayed-Action Preparations , Dose-Response Relationship, Drug , Dyspnea/etiology , Forced Expiratory Volume , Humans , Indans/administration & dosage , Indans/adverse effects , Patient Acuity , Pulmonary Disease, Chronic Obstructive/complications , Quinolones/administration & dosage , Quinolones/adverse effects , Randomized Controlled Trials as Topic , Scopolamine Derivatives/administration & dosage , Scopolamine Derivatives/adverse effects , Tiotropium Bromide
3.
Respir Med ; 107(2): 223-32, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23219347

ABSTRACT

BACKGROUND: Indacaterol is a once-daily, long-acting ß(2)-agonist bronchodilator that improves dyspnoea and health status in patients with moderate-to-severe COPD. While its bronchodilator effects have been shown to be maintained in different patient subgroups, effects on clinical outcomes in certain subgroups are not yet defined. METHODS: Post-hoc analysis of pooled clinical study data to investigate efficacy and safety of indacaterol compared with placebo and other long-acting bronchodilators (formoterol, salmeterol, open-label tiotropium) in patient subgroups defined by COPD severity (GOLD stage II or III; n = 4082) and ICS use at baseline (no/yes; n = 4088). Efficacy outcomes were trough (24-h post-dose) FEV(1), dyspnoea (transition dyspnoea index; TDI) and health status (St George's Respiratory Questionnaire; SGRQ) after 26 weeks. RESULTS: All active treatments significantly improved trough FEV(1) and dyspnoea compared with placebo, and all apart from open-label tiotropium improved health status compared with placebo. Among active treatments, indacaterol 150 µg had the best overall efficacy profile in the GOLD II and no-ICS subgroups. In the GOLD III and ICS subgroups, indacaterol 300 µg had the best overall efficacy, including a marked effect on dyspnoea (1.4-point improvement in TDI total score vs. placebo; p < 0.001). Within subgroups, the incidence of adverse events was similar between treatments. CONCLUSION: Indacaterol maintained its efficacy regardless of disease severity or use of concurrent ICS. Indacaterol 150 µg had the best overall efficacy profile in the GOLD stage II patients while, in patients with more severe disease, indacaterol 300 µg provided useful improvements in dyspnoea.


Subject(s)
Bronchodilator Agents/administration & dosage , Glucocorticoids/administration & dosage , Indans/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinolones/administration & dosage , Administration, Inhalation , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/therapeutic use , Adult , Aged , Albuterol/administration & dosage , Albuterol/analogs & derivatives , Albuterol/therapeutic use , Bronchodilator Agents/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Dyspnea/drug therapy , Dyspnea/etiology , Ethanolamines/administration & dosage , Ethanolamines/therapeutic use , Female , Forced Expiratory Volume/drug effects , Formoterol Fumarate , Glucocorticoids/therapeutic use , Humans , Indans/therapeutic use , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/physiopathology , Quinolones/therapeutic use , Randomized Controlled Trials as Topic , Salmeterol Xinafoate , Scopolamine Derivatives/administration & dosage , Scopolamine Derivatives/therapeutic use , Severity of Illness Index , Tiotropium Bromide , Treatment Outcome , Vital Capacity/drug effects
4.
Lancet Respir Med ; 1(7): 524-33, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24461613

ABSTRACT

BACKGROUND: We compared the efficacy and safety of indacaterol and tiotropium in patients with severe chronic obstructive pulmonary disease (COPD) and a history of at least one moderate to severe exacerbation in the previous 12 months. METHODS: In this multicentre, randomised, blinded, double-dummy, parallel group study, we enrolled patients aged 40 years or older with severe COPD and at least one exacerbation within the previous year. We used a computer-generated sequence to randomly allocate patients (1:1; stratified by baseline inhaled corticosteroid use, with the balance of treatments maintained at country level) to receive either indacaterol (150 µg) or tiotropium (18 µg) once-daily for 52 weeks. Our primary and key secondary objectives were to investigate whether indacaterol was non-inferior to tiotropium for trough forced expiratory volume in 1 s (FEV1) at week 12 (primary endpoint), and for rate of exacerbations at week 52 (secondary endpoint). Analysis populations for the primary and key secondary endpoints were per-protocol sets. The safety set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00845728. FINDINGS: Between March 16, 2009, and July 5, 2012, we enrolled and randomly allocated 3444 patients: 1723 to indacaterol and 1721 to tiotropium. At week 12, the estimated least squares mean trough FEV1 difference between the groups was -0.011 L (least squares mean with indacaterol [n=1450] 1.134 L [SE 0.008] vs tiotropium [n=1467] 1.145 L [0.008]; one-sided 97.5% CI lower limit -0.026 L; p<0.0001). The lower limit of the 97.5% CI was above the prespecified non-inferiority margin of -0.055 L, suggesting that indacaterol was non-inferior to tiotropium. Indacaterol did not show non-inferiority in terms of annualised exacerbation rates: 0.79 (indacaterol, n=1529) versus 0.61 (tiotropium, n=1543); ratio 1.29 (one-sided 97.5% CI upper limit 1.44). In the safety set, we recorded no between-group difference in the number of patients who had adverse events (indacaterol 1119 [65%] of 1721 patients vs tiotropium 1065 [62%] of 1718 patients) or serious adverse events (indacaterol, 263 [15%] of 1721 patients vs tiotropium, 255 [15%] of 1718 patients). Respiratory disorders, particularly worsening of COPD, were the most common adverse events (COPD: indacaterol, 747 [43%] of 1721 patients and tiotropium, 665 [39%] of 1718 patients) and serious adverse events (COPD: indacaterol, 147 [9%] of 1721 patients and tiotropium, 121 [7%] of 1718 patients). INTERPRETATION: Indacaterol and tiotropium provided clinically relevant improvements in lung function with comparable safety profiles. Tiotropium afforded greater protection from exacerbations, although the absolute number of events was small and the difference between treatments is of uncertain clinical importance. The present data offer evidence consistent with current guidelines. FUNDING: Novartis Pharma AG.


Subject(s)
Bronchodilator Agents/administration & dosage , Indans/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinolones/administration & dosage , Scopolamine Derivatives/administration & dosage , Adult , Aged , Double-Blind Method , Drug Administration Schedule , Female , Forced Expiratory Volume/drug effects , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , Tiotropium Bromide , Treatment Outcome , Vital Capacity/drug effects
5.
Respir Med ; 106(12): 1706-14, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23031496

ABSTRACT

BACKGROUND: Recent findings of rapid lung function decline in younger patients with moderate COPD severity suggest the need for effective early treatment. AIM: To evaluate the effectiveness of indacaterol as maintenance therapy in COPD patients not receiving other maintenance treatments. METHODS: Pooled data from three randomised, placebo-controlled studies provided a population of patients with moderate-to-severe COPD not receiving maintenance treatment at baseline and who received once-daily, double-blind treatment with indacaterol 150 µg, indacaterol 300 µg or placebo. Data from an open-label tiotropium treatment arm in one study were available for comparison. Efficacy evaluations included trough FEV1, dyspnoea (transition dyspnoea index, TDI) and health status (St George's Respiratory Questionnaire, SGRQ) at 6 months and risk of COPD exacerbations. RESULTS: The maintenance-naïve population comprised 232 (indacaterol 150 µg), 220 (indacaterol 300 µg) and 325 (placebo) patients, plus 156 (tiotropium) (30% of overall study population). Patients treated with indacaterol 150 and 300 µg had statistically significant improvements relative to placebo (p < 0.05) in trough FEV1 (170 and 180 mL), TDI total score (1.27 and 1.04 points), rescue use and SGRQ total score (-6.1 and -2.5 units) at 6 months. Patients receiving tiotropium had statistically significant improvements versus placebo (p < 0.05) in trough FEV1 (130 mL) and TDI total score (0.69 points). Exacerbations were rare and not significantly reduced by any treatment. Treatments were well tolerated. CONCLUSIONS: Indacaterol, given to patients with moderate-to-severe COPD not receiving other maintenance treatments, provided effective bronchodilation with significant, clinically relevant improvements in dyspnoea and health status compared with placebo.


Subject(s)
Bronchodilator Agents/therapeutic use , Indans/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinolones/therapeutic use , Double-Blind Method , Female , Forced Expiratory Volume/drug effects , Humans , Maintenance Chemotherapy/methods , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , Randomized Controlled Trials as Topic , Treatment Outcome , Vital Capacity/drug effects
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