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

PLoS One. 2015 Apr 20;10(4):e0124109. doi: 10.1371/journal.pone.0124109. eCollection 2015.

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).

Primary 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.

Trial registration: ClinicalTrials.gov NCT01340209.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adult
  • Aged
  • Asthma / drug therapy*
  • Bronchodilator Agents
  • Cholinergic Antagonists / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Forced Expiratory Volume
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Nebulizers and Vaporizers
  • Peak Expiratory Flow Rate
  • Surveys and Questionnaires
  • Time Factors
  • Tiotropium Bromide / administration & dosage*
  • Treatment Outcome
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Cholinergic Antagonists
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT01340209

Grant support

This work was supported by Boehringer Ingelheim who provided support in the form of salaries for authors ME, PMZ, SK and WS but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.