title: Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies.
abstract: Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy. Patients received once-daily olodaterol 5 or 10 μg, twice-daily formoterol 12 μg, or placebo. Co-primary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0-3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George's Respiratory Questionnaire. Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients received treatment. Olodaterol significantly improved FEV1 area under the curve from 0-3 hours versus placebo in both studies (with olodaterol 5 μg, 0.151 L and 0.129 L; with olodaterol 10 μg, 0.165 L and 0.154 L; for all comparisons P<0.0001) and FEV1 trough responses versus placebo (0.053-0.085 L; P<0.01), as did formoterol. Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo. Post hoc analysis using pattern mixture modeling (accounting for discontinuations) demonstrated statistical significance for olodaterol versus placebo. St George's Respiratory Questionnaire total score was significantly improved with olodaterol, but not formoterol, versus placebo. No safety signals were identified from adverse-event or other safety data. Once-daily olodaterol 5 μg and 10 μg is efficacious in patients with moderate to very severe chronic obstructive pulmonary disease on usual-care maintenance therapy, with a satisfactory safety profile.
authors.affiliation: Medical Clinic III for Pneumology, Allergology, Sleep and Respiratory Medicine, University Hospital Bochum-Bergmannsheil, Bochum, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Koch
authors.affiliation: NUPAIVA (Asthma Research Center), Universidade Federal de Santa Catarina, Santa Catarina, Brazil.
authors.forename: Emilio
authors.initials: E
authors.lastname: Pizzichini
authors.affiliation: Boehringer Ingelheim, Burlington, Ontario, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Hamilton
authors.affiliation: Boehringer Ingelheim, Burlington, Ontario, Canada.
authors.forename: Lorna
authors.initials: L
authors.lastname: Hart
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Korducki
authors.affiliation: Centro Médico Dra. De Salvo, Fundación Respirar, Buenos Aires, Argentina.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: De Salvo
authors.affiliation: Cardio-Thoracic and Vascular Department, University of Pisa, Pisa, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Paggiaro
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D019540:Area Under Curve; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004867:Equipment Design; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D020127:Recovery of Function; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D048588:Benzoxazines; D001993:Bronchodilator Agents; D004983:Ethanolamines; C549647:olodaterol; D000068759:Formoterol Fumarate
keywords: bronchodilator; chronic obstructive pulmonary disease; dyspnea; long-acting beta2-agonist