title: Once-daily tiotropium Respimat(®) 5 μg is an efficacious 24-h bronchodilator in adults with symptomatic asthma.
abstract: BACKGROUND
  Once-daily tiotropium Respimat(®) 5 μg is an efficacious add-on therapy to inhaled corticosteroids (ICS) with or without long-acting β2-agonists in patients with symptomatic asthma. The objective of this study was to investigate whether the dosing regimen of tiotropium (once- versus twice-daily), delivered via the Respimat(®) SoftMist™ inhaler, affected 24-h bronchodilator efficacy and safety versus placebo Respimat(®) in patients with asthma who were symptomatic despite medium-dose ICS therapy.
  
  
  METHODS
  A randomised, double-blind, placebo-controlled, crossover study with 4-week treatment periods of tiotropium 5 μg (once-daily, evening) and 2.5 μg (twice-daily, morning and evening). The primary efficacy end point was forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 24 h (AUC)(0-24h) at the end of each treatment period. Secondary end points included peak forced expiratory volume in 1 s measured within 24 h of the last evening inhalation (peak FEV1(0-24h)), trough FEV1 measured prior to evening dosing, morning and evening peak expiratory flow (PEFam and PEFpm) and pharmacokinetic assessments.
  
  
  RESULTS
  94 patients were randomised (mean age 44.3 years; mean asthma duration 21.3 years) and 89 (94.7%) completed the study. Significant and comparable bronchodilation was achieved over a 24-h period with both tiotropium dosing regimens. FEV1 AUC(0-24h) response (mean ± standard error) was significantly greater with both tiotropium dosing regimens (once-daily 5 μg: 158 ± 24 mL; twice-daily 2.5 μg; 149 ± 24 mL; both p < 0.01) when compared with placebo. Improvements in peak FEV1(0-24h), trough FEV1 and pre-dose PEFam/pm with both dosing regimens versus placebo were statistically significant (all p < 0.01), with no statistically significant differences between the tiotropium treatment regimens. Total systemic exposure and tolerability were comparable between treatment regimens.
  
  
  CONCLUSIONS
  Lung function improvements with tiotropium Respimat(®) add-on to medium-dose ICS were sustained and similar for once-daily 5 μg and twice-daily 2.5 μg, supporting tiotropium Respimat(®) 5 μg as a once-daily bronchodilator that provides efficacy over the whole 24-h dosing interval in patients with symptomatic asthma. ClinicalTrials.gov identifier: NCT01152450.
authors: CRS Clinical Research Services Mannheim GmbH, Grenadierstraße 1, 68167 Mannheim, Germany. Electronic address: w.timmer@inamed-cro.com.
authors: Wolfgang
authors: W
authors: Timmer
authors: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55218 Ingelheim am Rhein, Germany. Electronic address: petra.moroni-zentgraf@boehringer-ingelheim.com.
authors: Petra
authors: P
authors: Moroni-Zentgraf
authors: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55218 Ingelheim am Rhein, Germany. Electronic address: piet.cornelissen@boehringer-ingelheim.com.
authors: Piet
authors: P
authors: Cornelissen
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88400 Biberach an der Riss, Germany. Electronic address: anna.unseld@boehringer-ingelheim.com.
authors: Anna
authors: A
authors: Unseld
authors: NUPAIVA (Asthma Research Centre), Universidade Federal de Santa Catarina, Campus Universitário Reitor João David Ferreira Lima - Trindade, 88040-900 Florianópolis, SC, Brazil. Electronic address: pizzichi@matrix.com.br.
authors: Emilio
authors: E
authors: Pizzichini
authors: Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Langenbeckstraße 1, 55131 Mainz, Germany. Electronic address: roland.buhl@unimedizin-mainz.de.
authors: Roland
authors: R
authors: Buhl
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001317:Austria; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D018153:Czech Republic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004957:Estonia; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D005858:Germany; D006801:Humans; D007844:Latvia; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D000069447:Tiotropium Bromide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D000069447:Tiotropium Bromide
keywords: Anticholinergic drug; Asthma; Bronchodilator efficacy; Dosing regimen; Long-acting bronchodilator; Tiotropium