title: Long-Term Once-Daily Tiotropium Respimat® Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised, Placebo-Controlled Study.
abstract: BACKGROUND
  This study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β2-agonist (LABA).
  
  
  METHODS
  285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209).
  
  
  OBJECTIVE
  to describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV1) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score.
  
  
  RESULTS
  At Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV1 and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24.
  
  
  CONCLUSIONS
  The long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, significantly improved lung function and symptoms, supporting the long-term efficacy of the 5 μg dose.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01340209.
authors.affiliation: National Hospital Organization, Tokyo National Hospital, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
authors.affiliation: Department of Respiratory Medicine and Allergology, Kinki University, Faculty of Medicine, Osakasayama City, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tohda
authors.affiliation: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Engel
authors.affiliation: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Moroni-Zentgraf
authors.affiliation: Clinical Trial Management Department, Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kunimitsu
authors.affiliation: Medical Data Services Department, Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakamoto
authors.affiliation: Department of Clinical Research Center, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Adachi
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010366:Peak Expiratory Flow Rate; D011795:Surveys and Questionnaires; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D000069447:Tiotropium Bromide