Primary, secondary and additional efficacy endpoints (modified intent-to-treat population; efficacy estimand unless stated otherwise)
| BFF MDI 320/10 μg | BFF MDI 160/10μg | FF MDI 10 µg | |
| Patients, n | 619 | 617 | 607 |
| Primary endpoint | |||
| Change from baseline in morning pre-dose trough FEV1 (mL) at week 12# | |||
| n | 542 | 540 | 501 |
| LSM±se | 72±9.4 | 69±9.3 | 37±9.6 |
| LSM difference versus FF MDI (95% CI) | 34 (9–60) | 32 (7–57) | |
| p-value | 0.0081 | 0.0134 | |
| Secondary endpoints | |||
| Change from baseline in morning pre-dose trough FEV1 (mL) at week 12 (attributable estimand)# | |||
| n | 612 | 612 | 601 |
| LSM±se | 59±9.7 | 53±9.5 | 9±10.1 |
| LSM difference versus FF MDI (95% CI) | 50 (24–76) | 44 (18–70) | |
| p-value | 0.0002 | 0.0009 | |
| Time to first moderate/severe COPD exacerbation¶ | |||
| Patients with exacerbation n (%) | 220 (35.5) | 223 (36.1) | 241 (39.7) |
| HR versus FF MDI (95% CI) | 0.827 (0.688–0.995) | 0.803 (0.668–0.966) | |
| p-value | 0.0441 | 0.0198 | |
| SGRQ responder rate at week 12+ | |||
| Responders n (%) | 315 (51.98) | 331 (54.00) | 262 (43.96) |
| Difference versus FF MDI % (95% CI) | 7.55 (1.67–13.43) | 11.05 (5.18–16.91) | |
| p-value | 0.0121 | 0.0002 | |
| Change from baseline in mean daily rescue medication use (puffs·day-1) over 12 weeks# | |||
| n | 612 | 610 | 599 |
| LSM±se | −0.9±0.09 | −0.9±0.09 | −0.6±0.09 |
| LSM difference versus FF MDI (95% CI) | −0.32 (−0.56 to −0.08) | −0.29 (−0.53 to −0.05) | |
| p-value | 0.0097 | 0.0185 | |
| Additional endpoints | |||
| Rate of moderate/severe exacerbations per year§ | |||
| Adjusted rate of exacerbations+/−SE | 0.93±0.073 | 0.98±0.076 | 1.39±0.106 |
| Rate ratio versus FF MDI (95% CI) | 0.67 (0.54–0.82) | 0.71 (0.58–0.87) | |
| p-value | 0.0001ƒ | 0.0010ƒ | |
| Time to first moderate/severe COPD exacerbation in patients with a history of ≥2 COPD exacerbations in the last 12 months§ | |||
| Patients with exacerbation, n (%) | 93 (39.4) | 97 (40.2) | 106 (45.7) |
| HR versus FF MDI (95% CI) | 0.783 (0.590–1.039) | 0.799 (0.603–1.059) | |
| p-value | 0.0904 | 0.1178 | |
BFF: budesonide/formoterol fumarate dihydrate; MDI: metered dose inhaler; FF: formoterol fumarate dihydrate; FEV1: forced expiratory volume in 1 s; LSM: least squares mean; HR: hazard ratio; SGRQ: St George's Respiratory Questionnaire; COPD: chronic obstructive pulmonary disease. #: analysed by repeated measures linear mixed model; ¶: analysed by Cox regression; +: analysed by logistic regression model; §: analysed by negative binomial regression. Rate of exacerbations per year=total number of exacerbations / total years of exposure across all patients for the treatment. ƒ: p-values for this endpoint are considered nominal since these analyses were not under Type I error control.