title: Long-term safety and efficacy of combined tiotropium and olodaterol in Japanese patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  The efficacy and safety of once-daily tiotropium+olodaterol (T+O) (2.5/5µg or 5/5µg) for treating chronic obstructive pulmonary disease (COPD) have been demonstrated in the large, multinational, randomized, Phase III studies TONADO®1 and 2, which included 413 Japanese patients (~80 in each group). This study was conducted to supplement the TONADO®study data to assess long-term safety in ≥100 Japanese patients treated for 1 year in compliance with International Conference on Harmonisation guidelines. Efficacy was evaluated descriptively as a secondary end point.
  
  
  METHODS
  Patients were randomized to 52 weeks of double-blind treatment with once-daily T+O (2.5/5 or 5/5µg) or O (5µg) monotherapy via the Respimat®inhaler. We report the safety and efficacy data descriptively.
  
  
  RESULTS
  The incidence of adverse events (AEs) was comparable in the T+O 2.5/5µg (75.0%), T+O 5/5µg (85.4%), and O 5µg (80.5%) groups, with drug-related AEs being reported in 5.0%, 7.3%, and 4.9% of patients, respectively. Serious AEs were reported in 14 patients (11.5%). The change from baseline in forced expiratory volume in 1s (FEV1) area under the curve from 0 to 3h and trough FEV1were numerically higher in the T+O treatment groups than in the O monotherapy group throughout the study period. Overall safety of T+O was comparable to that in the TONADO®studies.
  
  
  CONCLUSIONS
  No safety concerns for long-term T+O treatment were identified in Japanese patients with COPD. A numerical improvement in lung function was observed with T+O treatment compared to O monotherapy.
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: ichinose@rm.med.tohoku.ac.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
authors.affiliation: Kishiwada City Hospital, 1001 Gakuhara-cho, Kishiwada, Osaka 596-8501, Japan. Electronic address: kch-43@kishiwada-hospital.com.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Kato
authors.affiliation: Nippon Boehringer Ingelheim Co. Ltd, 2-1-1 Osaki, Shinagawa-ku, Tokyo 141-6017, Japan. Electronic address: ayako.takizawa@boehringer-ingelheim.com.
authors.forename: Ayako
authors.initials: A
authors.lastname: Takizawa
authors.affiliation: Nippon Boehringer Ingelheim Co. Ltd, 2-1-1 Osaki, Shinagawa-ku, Tokyo 141-6017, Japan. Electronic address: wataru.sakamoto@boehringer-ingelheim.com.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakamoto
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany. Electronic address: lars.groenke@boehringer-ingelheim.com.
authors.forename: Lars
authors.initials: L
authors.lastname: Grönke
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany; Department of Sports Medicine, University of Tübingen, Hoppe-Seyler-Strasse 6, 72076 Tübingen, Germany. Electronic address: kay.tetzlaff@boehringer-ingelheim.com.
authors.forename: Kay
authors.initials: K
authors.lastname: Tetzlaff
authors.affiliation: Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: yfukuchi@tea.ocn.ne.jp.
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Fukuchi
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D044466:Asian People; D048588:Benzoxazines / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D048588:Benzoxazines; D001993:Bronchodilator Agents; C549647:olodaterol; D000069447:Tiotropium Bromide
keywords: Chronic obstructive pulmonary disease; Japanese patients; Olodaterol; Tiotropium