Background
Methods
Patients
Study design and treatment
Efficacy assessments
Pharmacokinetics
Safety and tolerability assessments
Statistical methods
Results
Patient disposition
Characteristic | Patients (N = 70) | Median | Quartiles | |
---|---|---|---|---|
Q1 | Q3 | |||
Age (years), mean (SD) | 61.2 (7.7) | 62.0 | 56.0 | 66.0 |
BMI (kg/m2), mean (SD) | 27.35 (4.20) | 27.21 | 24.25 | 30.12 |
Gender (male), n (%) | 44 (62.86) | |||
Race (Caucasian), n (%) | 69 (98.57) | |||
Current smoker, n (%) | 41 (58.57) | |||
Smoking history (pack-years), mean (SD) | 48.96 (27.98) | 41.25 | 31.00 | 61.20 |
Severity of airflow limitation, n (%) | ||||
Moderate (GOLD Stage II) | 49 (70.0) | |||
Severe (GOLD Stage III) | 21 (30.0) | |||
Post-bronchodilator FEV1 (L) | ||||
Mean (SD) | 1.72 (0.57) | 1.71 | 1.20 | 2.04 |
% predicted, mean (SD) | 58.03 (12.57) | 57.95 | 49.20 | 68.90 |
Post-bronchodilator FVC (L) | ||||
Mean (SD) | 3.57 (0.99) | 3.52 | 2.76 | 4.23 |
% predicted, mean (SD) | 97.64 (16.62) | 98.70 | 86.50 | 107.80 |
FEV1/FVC ratio (%), mean (SD) | 48.53 (10.28) | 48.10 | 40.50 | 56.30 |
Bronchial reversibility (%), mean (SD)a | 15.74 (13.25) | 13.25 | 6.90 | 20.20 |
Prior COPD medicationb, n (%) | ||||
SABA | 66 (94.29) | |||
LAMA | 17 (24.29) | |||
LABA/ICS | 17 (24.29) | |||
LABA | 16 (22.86) | |||
ICS | 8 (11.43) | |||
SABA + SAMA | 4 (5.71) | |||
Xanthines | 4 (5.71) | |||
SAMA | 2 (2.86) | |||
Influenza vaccine | 1 (1.43) | |||
Oxygen | 1 (1.43) |
Efficacy
Primary efficacy variable
Secondary efficacy variables
FEV1 variable (L) | Comparison | Abediterol 0.625 μg (N = 67) | Abediterol 2.5 μg (N = 66) | Abediterol 5 μg (N = 66) | Abediterol 10 μg (N = 67) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
LS mean | 95 % CI | p-value | LS mean | 95 % CI | p-value | LS mean | 95 % CI | p-value | LS mean | 95 % CI | p-value | ||
Normalised AUC0-12 at Day 1 | vs placebo | 0.164 | 0.134, 0.195 | <0.0001 | 0.246 | 0.216, 0.277 | <0.0001 | 0.255 | 0.224, 0.285 | <0.0001 | 0.283 | 0.252, 0.313 | <0.0001 |
vs indacaterol | 0.027 | −0.004, 0.057 | 0.0826 | 0.109 | 0.079, 0.139 | <0.0001 | 0.117 | 0.087, 0.148 | <0.0001 | 0.145 | 0.115, 0.176 | <0.0001 | |
Normalised AUC12-24 at Day 1 | vs placebo | 0.131 | 0.095, 0.167 | <0.0001 | 0.227 | 0.192, 0.263 | <0.0001 | 0.264 | 0.228, 0.299 | <0.0001 | 0.290 | 0.254, 0.326 | <0.0001 |
vs indacaterol | −0.002 | −0.038, 0.035 | 0.9296 | 0.095 | 0.058, 0.131 | <0.0001 | 0.131 | 0.095, 0.167 | <0.0001 | 0.157 | 0.121, 0.193 | <0.0001 | |
Normalised AUC0-24 at Day 1 | vs placebo | 0.148 | 0.118, 0.179 | <0.0001 | 0.237 | 0.206, 0.268 | <0.0001 | 0.260 | 0.229, 0.291 | <0.0001 | 0.286 | 0.255, 0.317 | <0.0001 |
vs indacaterol | 0.014 | −0.017, 0.045 | 0.3799 | 0.102 | 0.071, 0.134 | <0.0001 | 0.125 | 0.094, 0.157 | <0.0001 | 0.152 | 0.120, 0.183 | <0.0001 | |
Peak FEV1 at Day 1 | vs placebo | 0.185 | 0.147, 0.223 | <0.0001 | 0.255 | 0.217, 0.292 | <0.0001 | 0.257 | 0.219, 0.295 | <0.0001 | 0.285 | 0.247, 0.323 | <0.0001 |
vs indacaterol | 0.019 | −0.019, 0.057 | 0.3350 | 0.089 | 0.050, 0.127 | <0.0001 | 0.091 | 0.053, 0.129 | <0.0001 | 0.119 | 0.081, 0.157 | <0.0001 |
FVC variable (L) | Comparison | LS mean differences in changes from baseline | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Abediterol 0.625 μg (N = 67) | Abediterol 2.5 μg (N = 66) | Abediterol 5 μg (N = 66) | Abediterol 10 μg (N = 67) | ||||||||||
LS mean | 95 % CI | p- value | LS mean | 95 % CI | p-value | LS mean | 95 % CI | p-value | LS mean | 95 % CI | p-value | ||
Normalised AUC0-12 at Day 1 | vs placebo | 0.227 | 0.169, 0.284 | <0.0001 | 0.280 | 0.222, 0.337 | <0.0001 | 0.301 | 0.243, 0.358 | <0.0001 | 0.347 | 0.289, 0.405 | <0.0001 |
vs indacaterol | 0.010 | −0.047, 0.068 | 0.7258 | 0.063 | 0.05, 0.121 | 0.0323 | 0.084 | 0.027, 0.142 | 0.0044 | 0.130 | 0.072, 0.188 | <0.0001 | |
Normalised AUC12-24 at Day 1 | vs placebo | 0.182 | 0.114, 0.249 | <0.0001 | 0.308 | 0.201, 0.376 | <0.0001 | 0.352 | 0.285, 0.420 | <0.0001 | 0.386 | 0.319, 0.454 | <0.0001 |
vs indacaterol | −0.026 | −0.094, 0.042 | 0.4471 | 0.100 | 0.031, 0.166 | 0.0045 | 0.144 | 0.076, 0.212 | <0.0001 | 0.178 | 0.110, 0.247 | <0.0001 | |
Normalised AUC0-24 at Day 1 | vs placebo | 0.208 | 0.153, 0.263 | <0.0001 | 0.294 | 0.239, 0.349 | <0.0001 | 0.332 | 0.276, 0.387 | <0.0001 | 0.369 | 0.313, 0.424 | <0.0001 |
vs indacaterol | −0.007 | −0.063, 0.048 | 0.7996 | 0.079 | 0.023, 0.135 | 0.0058 | 0.117 | 0.061, 0.172 | <0.0001 | 0.154 | 0.098, 0.209 | <0.0001 | |
Peak FVC at Day 1 | vs placebo | 0.152 | 0.035, 0.270 | 0.0110 | 0.191 | 0.074, 0.309 | 0.0015 | 0.201 | 0.083, 0.318 | 0.0009 | 0.244 | 0.127, 0.361 | <0.0001 |
vs indacaterol | 0.013 | −0.104, 0.131 | 0.8219 | 0.052 | −0.065, 0.170 | 0.3829 | 0.062 | −0.056, 0.179 | 0.3024 | 0.105 | −0.012, 0.222 | 0.0795 |
Pharmacokinetics
Parameter (unit) | Abediterol 0.625 μg | Abediterol 2.5 μg | Abediterol 5 μg | Abediterol 10 μg | ||||
---|---|---|---|---|---|---|---|---|
(n = 19) | (n = 19) | (n = 19) | (n = 20) | |||||
mean | (SD) | mean | (SD) | mean | (SD) | mean | (SD) | |
Cmax (pg/mL) | 0.374 | 0.195 | 1.230 | 0.637 | 2.24 | 0.927 | 5.10 | 2.67 |
tmaxa (h) | 0.50 | 0.25–8 | 0.50 | 0.22–1.5 | 0.45 | 0.25–1.5 | 0.50 | 0.25–0.75 |
t½ (h) | 27.5b | 9.02 | 17.4c | 6.76 | 16.0d | 5.04 | 15.1e | 3.35 |
AUC0-t (pg.h/mL) | 2.29 | 1.17 | 7.84 | 2.82 | 13.3 | 4.48 | 28.0 | 11.0 |
AUC (pg.h/mL) | 5.95b | 2.66 | 12.5c | 6.01 | 19.7d | 4.48 | 38.1e | 14.1 |
CL/f (L/h) | 119b | 40 | 252c | 135 | 268d | 70.6 | 310e | 161 |
Vz/f (L) | 4345b | 753 | 5736c | 2629 | 6219d | 2675 | 7060e | 5199 |
Safety and tolerability
TEAE, n (%) | Number of patients (%) reporting TEAE | ||||||
---|---|---|---|---|---|---|---|
Placebo (N = 68) | Indacaterol 150 μg (N = 68) | Abediterol | Total (N = 70) | ||||
0.625 μg (N = 67) | 2.5 μg (N = 66) | 5 μg (N = 66) | 10 μg (N = 67) | ||||
Any | 9 (13.2) | 10 (14.7) | 7 (10.4) | 5 (7.6) | 6 (9.1) | 9 (13.4) | 32 (45.7) |
Nasopharyngitis | 2 (2.9) | 5 (7.4) | 4 (6.0) | 1 (1.5) | 1 (1.5) | 2 (3.0) | 15 (21.4) |
Headache | 3 (4.4) | 0 | 1 (1.5) | 0 | 2 (3.0) | 2 (3.0) | 8 (11.4) |
Dyspnoea | 0 | 2 (2.9) | 0 | 0 | 0 | 0 | 2 (2.9) |