Effect of aclidinium bromide/formoterol fumarate fixed-dose combination (FDC) on night-time and early morning symptoms in COPD

Background Aclidinium/formoterol FDC is in clinical development for the treatment of COPD. We studied the effects of twice-daily aclidinium/formoterol FDC on night-time and early morning symptoms in patients with stable, moderate to severe COPD. Methods ACLIFORM and AUGMENT were multinational, double-blind, placebo- and active-controlled, parallel-group studies. Patients were randomised to receive placebo, aclidinium 400 µg, formoterol 12 µg, FDC 400/6 µg or FDC 400/12 µg. Patients used an eDiary to report night-time and early morning symptoms, which also contained other questions related to symptom impacts. Results The ITT population included 3394 patients (mean age 63.5 years; 60.5% male; moderate COPD 58.6%; baseline night-time symptom severity [mean±SD] 1.1±0.7, early morning symptom severity 1.3±0.7). Over 24 weeks, overall night-time symptom severity significantly improved with FDC vs placebo (FDC 400/12 µg: -0.11; 400/6 µg: -0.14), formoterol (FDC 400/12 µg: -0.05; 400/6 µg: -0.08) and aclidinium (FDC 400/12 µg: -0.09; 400/6 µg: -0.12) (all p<0.05). Overall, early morning symptom severity also improved with FDC vs placebo (FDC 400/12 µg: -0.12; 400/6 µg: -0.14), formoterol (FDC 400/12 µg: -0.06; 400/6 µg: -0.08) and aclidinium (FDC 400/12 µg: -0.09; 400/6 µg: -0.11) (all p<0.01). Night-time and early morning cough, wheezing, breathlessness and difficulty bringing up phlegm were significantly improved with FDC vs placebo (all p<0.05, both doses). Conclusions These data suggest that aclidinium/formoterol FDC improves overall night-time and early morning symptom severity in patients with moderate to severe COPD compared with placebo and monotherapy.