Figures
- Figure 1–
Differences between active treatments (▴: salmeterol; ▪: indacaterol) over placebo for trough forced expiratory volume in 1 s (FEV1). Data are presented as least squares means and whiskers represent 95% CI. Patient numbers analysed at day 2, week 12 (primary end-point) and week 26, respectively, were 317, 320 and 300 (indacaterol), 320, 317 and 291 (salmeterol), and 321, 316 and 274 (placebo). ---: pre-specified 120 mL clinically important difference versus placebo. #: p<0.001 versus placebo; ¶: p<0.001 for indacaterol versus salmeterol.
- Figure 2–
Changes from baseline in St George’s Respiratory Questionnaire (SGRQ) total score. Data are presented as unadjusted mean±se. Patient numbers analysed at weeks 4, 8, 12 and 26 were, respectively, 311, 304, 309 and 299 (indacaterol; ▪), 302, 300, 301 and 292 (salmeterol; ▴), and 298, 294, 294 and 274 (placebo; •). ---: clinically important change. Note that a downward shift of the curve indicates improvement on this graph.
- Figure 3–
Changes from baseline in transition dyspnoea index (TDI) total score. Data are presented as unadjusted mean±se. Patient numbers analysed at weeks 4, 8, 12 and 26 were, respectively, 309, 300, 303 and 297 (indacaterol; ▪), 298, 292, 296 and 289 (salmeterol; ▴), and 295, 282, 286 and 272 (placebo; •). ---: clinically important change.
Tables
- Table 1– Disposition of patients during the study
Indacaterol Salmeterol Placebo Randomised 333 (100.0) 334 (100.0) 335 (100.0) Treated 330 (99.1) 333 (99.7) 335 (100.0) Completed 289 (86.8) 284 (85.0) 265 (79.1) Discontinued 44 (13.2) 50 (15.0) 70 (20.9) Primary reason for premature discontinuation Adverse event(s) 18 (5.4) 16 (4.8) 13 (3.9) Protocol deviation 9 (2.7) 11 (3.3) 13 (3.9) Subject withdrew consent 8 (2.4) 12 (3.6) 22 (6.6) Abnormal lab value(s) 2 (0.6) 1 (0.3) 2 (0.6) Abnormal test procedure result(s) 2 (0.6) 1 (0.3) 1 (0.3) Lost to follow-up 2 (0.6) 5 (1.5) 2 (0.6) Unsatisfactory therapeutic effect 1 (0.3) 2 (0.6) 15 (4.5) Administrative problems 1 (0.3) 1 (0.3) 0 Death 1 (0.3) 0 3 (0.9) Patient's inability to use the device 0 1 (0.3) 0 Intention-to-treat population 330 (99.1) 333 (99.7) 335 (100.0) Safety population 330 (99.1) 333 (99.7) 335 (100.0) Data are presented as n (%).
- Table 2– Demographics and baseline characteristics
Indacaterol Salmeterol Placebo Subjects n 330 333 335 Age yrs 63±8.7 63±9.2 64±8.6 Males/females % 72/28 75/25 77/23 Duration of COPD yrs 6.5±5.7 6.4±5.7 6.6±5.8 Ex-smokers/smokers % 54/46 54/46 55/45 Smoking history pack-yrs 40±17.0 40±16.7 41±18.9 ICS use % 45 46 40 FEV1# L 1.5±0.49 1.5±0.49 1.5±0.47 FEV1# % pred 54±14.0 53±13.6 53±14.2 FEV1/FVC# 0.5±0.10 0.5±0.10 0.5±0.11 Reversibility to salbutamol % 12±15.3 11±13.9 13±16.4 SGRQ total score 43±18.6 44±18.4 44±18.1 BDI score 6.8±2.1 6.6±2.2 6.6±2.0 Salbutamol use puffs·day−1 3.2±3.6 3.1±3.4 3.2±3.2 Data are presented as mean±sd, unless otherwise stated. COPD: chronic obstructive pulmonary disease; ICS: inhaled corticosteroid; FEV1: forced expiratory volume in 1 s; % pred: % predicted; FVC: forced vital capacity; SGRQ: St George's Respiratory Questionnaire; BDI: baseline dyspnoea index. #: post-salbutamol.
- Table 3– Health status responder analysis
Week Placebo % Indacaterol Salmeterol % OR (95% CI) p-value % OR (95% CI) p-value 4 38.9 46.9 1.48 (1.04–2.11) <0.05 46.0 1.46 (1.02–2.09) <0.05 8 41.5 53.9 1.78 (1.26–2.51) <0.001 48.7 1.45 (1.03–2.05) <0.05 12 39.1 57.9 2.41 (1.69–3.42) <0.001 46.8 1.52 (1.06–2.16) <0.05 26 38.0 52.8 1.96 (1.37–2.81) <0.001 48.6 1.72 (1.19–2.48) <0.01 Percentage of patients achieving minimal clinically important differences (MCID) in St George’s Respiratory Questionnaire score (≥4-point increase), and odds ratios and p-values versus placebo for likelihood of achieving the MCID.
- Table 4– Symptom-related outcomes and peak expiratory flow (PEF) over 26 weeks
Placebo Indacaterol Salmeterol Change from baseline in as-needed salbutamol use puffs·day−1 -0.3±0.16 -1.3±0.16# -1.2±0.16# Days with no as-needed salbutamol use % 42.2±2.59 59.7±2.58#,¶ 54.7±2.58# Change from baseline in morning PEF L·min−1 -0.8±2.74 25.3±2.72#,+ 15.2±2.73# Change from baseline in evening PEF L·min−1 -2.3±2.82 23.4±2.80#,+ 12.7±2.80# Nights with no awakenings % 65.3±1.64 71.6±1.61# 70.8±1.62§ Days with no daytime symptoms % 6.2±1.13 10.5±1.11§ 8.9±1.11ƒ Days able to perform usual activities % 34.8±1.77 42.5±1.75#,¶ 38.2±1.75 Data are presented as least squares mean±se. Patient numbers evaluated for the different outcomes were 301–304 for placebo, 306–310 for indacaterol and 303–310 for salmeterol. #: p<0.001 versus placebo; ¶: p<0.05 versus salmeterol; +: p<0.001 versus salmeterol; §: p<0.01 versus placebo; ƒ: p<0.05 versus placebo.
- Table 5– Adverse events
Indacaterol Salmeterol Placebo Subjects n 330 333 335 Patients with any adverse event(s) 169 (51.2) 152 (45.6) 156 (46.6) COPD worsening 60 (18.2) 51 (15.3) 65 (19.4) Nasopharyngitis 24 (7.3) 29 (8.7) 21 (6.3) Upper respiratory tract infection Bacterial 14 (4.2) 3 (0.9) 5 (1.5) Viral 10 (3.0) 3 (0.9) 7 (2.1) Lower respiratory tract infection 9 (2.7) 13 (3.9) 8 (2.4) Back pain 7 (2.1) 12 (3.6) 6 (1.8) Data are presented as n (%) unless otherwise stated. Most common events listed for ≥3% of patients in either indacaterol or salmeterol groups. COPD: chronic obstructive pulmonary disease.
