Long-term safety of aclidinium bromide/formoterol fumarate fixed-dose combination: Results of a randomized 1-year trial in patients with COPD.

TRIAL DESIGN: This was a one-year, Phase III randomized, double-blind, parallel-group, active-control study investigating the long-term safety and tolerability of twice-daily aclidinium 400 µg/formoterol 12 µg versus formoterol 12 µg. METHODS: Eligible patients were male or female, current or ex-smokers (history of ≥10 pack-years) aged ≥40 years with a diagnosis of moderate to severe chronic obstructive pulmonary disease (COPD): post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <70%, and post-bronchodilator FEV1≥30% and <80% predicted. Patients were randomized 2:1 to twice-daily aclidinium 400 µg/formoterol 12 µg or formoterol 12 µg, administered via a multidose dry powder inhaler (Genuair™/Pressair(®))(1). The objective was to evaluate the one-year safety of aclidinium 400 µg/formoterol 12 µg versus formoterol 12 µg. RESULTS: All 590 patients were included in the safety population; 392 patients received aclidinium 400 µg/formoterol 12 µg and 198 patients received formoterol 12 µg. Of these, 581 patients were included in the intent-to-treat (ITT) population (385 patients received aclidinium 400 µg/formoterol 12 µg; 196 patients received formoterol 12 µg). In the safety population, the percentage of patients with ≥1 treatment-emergent adverse event was similar between aclidinium 400 µg/formoterol 12 µg (71.4%) and formoterol 12 µg (65.7%). Mean baseline post-bronchodilator FEV1 was 51.3% of predicted (ITT population). Aclidinium 400 µg/formoterol 12 µg significantly improved morning pre-dose (trough) FEV1 and trough FVC versus formoterol 12 µg at each assessment, with improvements at Week 1 (least squares mean difference [LSMD]: 87.4 mL and 157.8 mL, respectively) maintained at study end (LSMD: 81.5 mL and 185.4 mL, respectively). CONCLUSIONS: Aclidinium 400 µg/formoterol 12 µg was well tolerated, with a safety profile similar to formoterol 12 µg and consistent with that seen in two Phase III studies. Additionally, aclidinium 400 µg/formoterol 12 µg improved lung function versus formoterol 12 µg, with a sustained effect over one year.