Once-daily tiotropium Respimat^® 5 μg is an efficacious 24-h bronchodilator in adults with symptomatic asthma

Summary

Introduction

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 FEV_1(0–24h)), trough FEV₁ measured prior to evening dosing, morning and evening peak expiratory flow (PEF_am and PEF_pm) 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 FEV_1(0–24h), trough FEV₁ and pre-dose PEF_am/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.