Journal Article

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

Kunimitsu, Satoko, Engel, Michael, Adachi, Mitsuru, Ohta, Ken, Moroni-Zentgraf, Petra, Sakamoto, Wataru, Ichinose, Masakazu, Tohda, Yuji

2015

Overview

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). 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). 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. 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. 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. ClinicalTrials.gov NCT01340209.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acetylcholine receptors / Administration, Inhalation / Adolescent / Adrenal Cortex Hormones - administration & dosage / Adrenergic beta-2 Receptor Agonists - administration & dosage / Adult / Aged / Anticholinergics / Asthma / Asthma - drug therapy / Bronchitis / Bronchodilator Agents / Bronchodilators / Cholinergic Antagonists - administration & dosage / Chronic obstructive pulmonary disease / Clinical trials / Corticoids / Corticosteroids / Double-Blind Method / Drug Administration Schedule / Drug dosages / Effectiveness / Female / Flow rates / Flow velocity / Forced Expiratory Volume / Gastroenteritis / Hospitals / Humans / Japan / Lungs / Male / Medicine / Middle Aged / Nebulizers and Vaporizers / Patients / Peak Expiratory Flow Rate / Pharyngitis / Randomization / Respiratory diseases / Respiratory function / Rhinopharyngitis / Safety / Surveys and Questionnaires / Systematic review / Time Factors / Tiotropium Bromide - administration & dosage / Treatment Outcome / Young Adult