PMID- 28274527 OWN - NLM STAT- MEDLINE DCOM- 20170919 LR - 20221207 IS - 2212-5353 (Electronic) IS - 2212-5345 (Linking) VI - 55 IP - 2 DP - 2017 Mar TI - Long-term safety and efficacy of combined tiotropium and olodaterol in Japanese patients with chronic obstructive pulmonary disease. PG - 121-129 LID - S2212-5345(16)30116-2 [pii] LID - 10.1016/j.resinv.2016.09.004 [doi] AB - BACKGROUND: The efficacy and safety of once-daily tiotropium+olodaterol (T+O) (2.5/5microg or 5/5microg) for treating chronic obstructive pulmonary disease (COPD) have been demonstrated in the large, multinational, randomized, Phase III studies TONADO((R)) 1 and 2, which included 413 Japanese patients (~80 in each group). This study was conducted to supplement the TONADO((R)) 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 5/5microg) or O (5microg) monotherapy via the Respimat((R)) inhaler. We report the safety and efficacy data descriptively. RESULTS: The incidence of adverse events (AEs) was comparable in the T+O 2.5/5microg (75.0%), T+O 5/5microg (85.4%), and O 5microg (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 (FEV(1)) area under the curve from 0 to 3h and trough FEV(1) were 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((R)) 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. CI - Copyright (c) 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved. FAU - Ichinose, Masakazu AU - Ichinose M AD - 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. FAU - Kato, Motokazu AU - Kato M AD - Kishiwada City Hospital, 1001 Gakuhara-cho, Kishiwada, Osaka 596-8501, Japan. Electronic address: kch-43@kishiwada-hospital.com. FAU - Takizawa, Ayako AU - Takizawa A AD - Nippon Boehringer Ingelheim Co. Ltd, 2-1-1 Osaki, Shinagawa-ku, Tokyo 141-6017, Japan. Electronic address: ayako.takizawa@boehringer-ingelheim.com. FAU - Sakamoto, Wataru AU - Sakamoto W AD - Nippon Boehringer Ingelheim Co. Ltd, 2-1-1 Osaki, Shinagawa-ku, Tokyo 141-6017, Japan. Electronic address: wataru.sakamoto@boehringer-ingelheim.com. FAU - Gronke, Lars AU - Gronke L AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany. Electronic address: lars.groenke@boehringer-ingelheim.com. FAU - Tetzlaff, Kay AU - Tetzlaff K AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany; Department of Sports Medicine, University of Tubingen, Hoppe-Seyler-Strasse 6, 72076 Tubingen, Germany. Electronic address: kay.tetzlaff@boehringer-ingelheim.com. FAU - Fukuchi, Yoshinosuke AU - Fukuchi Y AD - Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: yfukuchi@tea.ocn.ne.jp. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20161222 PL - Netherlands TA - Respir Investig JT - Respiratory investigation JID - 101581124 RN - 0 (Benzoxazines) RN - 0 (Bronchodilator Agents) RN - VD2YSN1AFD (olodaterol) RN - XX112XZP0J (Tiotropium Bromide) SB - IM MH - Administration, Inhalation MH - Adult MH - Aged MH - Asian People MH - Benzoxazines/*administration & dosage MH - Bronchodilator Agents/*administration & dosage MH - Double-Blind Method MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - Humans MH - Male MH - Middle Aged MH - Pulmonary Disease, Chronic Obstructive/*drug therapy MH - Time Factors MH - Tiotropium Bromide/*administration & dosage MH - Treatment Outcome OTO - NOTNLM OT - Chronic obstructive pulmonary disease OT - Japanese patients OT - Olodaterol OT - Tiotropium EDAT- 2017/03/10 06:00 MHDA- 2017/09/20 06:00 CRDT- 2017/03/10 06:00 PHST- 2016/07/18 00:00 [received] PHST- 2016/09/23 00:00 [revised] PHST- 2016/09/27 00:00 [accepted] PHST- 2017/03/10 06:00 [entrez] PHST- 2017/03/10 06:00 [pubmed] PHST- 2017/09/20 06:00 [medline] AID - S2212-5345(16)30116-2 [pii] AID - 10.1016/j.resinv.2016.09.004 [doi] PST - ppublish SO - Respir Investig. 2017 Mar;55(2):121-129. doi: 10.1016/j.resinv.2016.09.004. Epub 2016 Dec 22.