A randomised double-blind, placebo-controlled, long-term extension study of the efficacy, safety and tolerability of fixed-dose combinations of aclidinium/formoterol or monotherapy in the treatment of chronic obstructive pulmonary disease.
Aclidinium bromide/formoterol fumarate (AB/FF) 400/12 μg efficacy and safety was demonstrated in two 6-month Phase III studies (AUGMENT and ACLIFORM) and a 12-month study in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This Phase III, double-blind, placebo-controlled, 6-month AUGMENT extension investigated the long-term safety and tolerability of AB/FF 400/12 μg (NCT01572792).



Patients were randomised in AUGMENT (1:1:1:1:1) to twice-daily AB/FF 400/12 μg, AB/FF 400/6 μg, AB 400 μg, FF 12 μg or placebo. Patients completing AUGMENT were invited to continue the same treatment in the extension. Adverse events (AEs), major adverse cardiovascular events (MACE), laboratory tests, electrocardiograms and vital signs were recorded. Efficacy was assessed.



Of 1322 patients completing AUGMENT, 921 enrolled and 780 completed the extension. AE incidence was low and comparable across treatment groups; most common were nasopharyngitis (range 4.8%-9.3%), urinary tract infection (range 4.1%-8.8%) and upper respiratory tract infection (range 2.7%-5.5%). Serious AEs (SAEs) and MACE were low (ranges 6.8%-7.7% and 0.5%-1.5%, respectively). Significant improvements in bronchodilation and dyspnoea were maintained over 52 weeks versus placebo. Trends towards improvements in other symptoms and health status were observed versus placebo and monotherapies. AB/FF combinations increased the time to first exacerbation by approximately 30% versus placebo (p < 0.05).



AB/FF 400/12 μg was well tolerated over 52 weeks with low incidences of AEs, SAEs and MACE that were comparable across treatment groups. Improvements in bronchodilation, symptoms and health status were maintained across 52 weeks.
University of Toronto, Toronto, ON, Canada. Electronic address: tonydurzo@sympatico.ca.
Anthony
A
D'Urzo
University of Nebraska Medical Center, Omaha, NE, USA; AstraZeneca, Cambridge, UK. Electronic address: stephen.rennard@astrazeneca.com.
Stephen
S
Rennard
Clinical Research Institute, Medford, OR, USA. Electronic address: ekerwin@allergyasthmaso.com.
Edward
E
Kerwin
University of North Carolina, Chapel Hill, NC, USA. Electronic address: james_donohue@med.unc.edu.
James F
JF
Donohue
AstraZeneca R&D Centre, Barcelona, Spain. Electronic address: alejhandra.lei@astrazeneca.com.
Alejhandra
A
Lei
AstraZeneca R&D Centre, Barcelona, Spain. Electronic address: eduard.molins@astrazeneca.com.
Eduard
E
Molins
Formerly of Almirall S.A., Barcelona, Spain.
Anne
A
Leselbaum
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000368:Aged; D001993:Bronchodilator Agents / Q000494:pharmacology; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004417:Dyspnea / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D014326:Tropanes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D014326:Tropanes; C542859:aclidinium bromide; D000068759:Formoterol Fumarate
Aclidinium; COPD; Clinical trial; Combination therapy; Formoterol