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



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.



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).



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.
Division of Pulmonary Medicine, University of North Carolina, 130 Mason Farm Rd Suite 4124, Chapel Hill NC27599, USA. Electronic address: james_donohue@med.unc.edu.
James F
JF
Donohue
Clinical Research Center of Alabama, 504 Brookwood Boulevard, Suite 250, Birmingham, AL 35209, USA. Electronic address: WSoong@alabamaallergy.com.
Weily
W
Soong
Forest Laboratories LLC, a wholly owned subsidiary of Allergan plc, Harborside Financial Center, Plaza V, Jersey City, NJ 07311, USA. Electronic address: Renee.Wu@actavis.com.
Xiao
X
Wu
Forest Laboratories LLC, a wholly owned subsidiary of Allergan plc, Harborside Financial Center, Plaza V, Jersey City, NJ 07311, USA. Electronic address: Pomy.Shrestha@actavis.com.
Pomy
P
Shrestha
Global Medicines Development, AstraZeneca PLC, Pont Reixat, 5, 08960 Sant Just Desvern, Barcelona, Spain. Electronic address: alejhandra.lei@astrazeneca.com.
Alejhandra
A
Lei
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000368:Aged; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D004361:Drug Tolerance; D058995:Dry Powder Inhalers; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012907:Smoking / Q000453:epidemiology; D016896:Treatment Outcome; D014326:Tropanes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014797:Vital Capacity / Q000187:drug effects
D058666:Adrenergic beta-2 Receptor Agonists; D018727:Muscarinic Antagonists; D014326:Tropanes; C542859:aclidinium bromide; D000068759:Formoterol Fumarate
Aclidinium; COPD; Formoterol; LABA; LAMA; Muscarinic antagonist