Kai-Michael Beeh1, Anne-Marie Kirsten2, Daniel Dusser3, Ashish Sharma4, Piet Cornelissen5, Ralf Sigmund6, Petra Moroni-Zentgraf5, Ronald Dahl7. 1. 1 Insaf Institut für Atemwegsforschung GmbH , Wiesbaden, Germany . 2. 2 Pulmonary Research Institute at LungClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research , Grosshansdorf, Germany . 3. 3 Pulmonary Department and Adult Cystic Fibrosis Center, Université Paris Descartes, Cochin Hospital , Paris, France . 4. 4 Translational Medicine and Clinical Pharmacology , Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany . 5. 5 TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim am Rhein, Germany . 6. 6 Global Biometrics and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach an der Riss, Germany . 7. 7 Allergy Centre, Odense University Hospital , Odense, Denmark .
Abstract
BACKGROUND: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat® 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacokinetic sample contamination resulting from improper sampling procedure, sample handling, or device handling during priming and subsequent inhalation procedure. METHODS: A Phase II, randomized, double-blind, two-way crossover study (NCT01696071) comparing two daily dosing regimens of tiotropium for 4 weeks, once-daily 5 μg (evening dosing) or twice-daily 2.5 μg (morning and evening dosing), as add-on to maintenance therapy with ICS (400-800 μg budesonide or equivalent) as controller medication. There was no washout between treatment periods. RESULTS: An increase in the area under the curve of the 24-hour forced expiratory volume in 1 second profile from study baseline was observed following once-daily tiotropium 5 μg (217 mL) and twice-daily 2.5 μg (219 mL), with no difference between the two regimens (-2 mL [95% confidence interval: -38, 34]). In a subset of the study population, total tiotropium exposure, expressed as area under the plasma concentration versus time curve over 24 hours, was comparable between dosing regimens. Unexpected tiotropium plasma levels were observed in two patients, possibly because of contamination. CONCLUSIONS: The observed bronchodilator efficacy over 24 hours was similar with once-daily tiotropium 5 μg and twice-daily 2.5 μg as add-on to ICS therapy, supporting the suitability of once-daily dosing to provide sustained improvements in lung function in adults with symptomatic asthma.
RCT Entities:
BACKGROUND: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat® 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacokinetic sample contamination resulting from improper sampling procedure, sample handling, or device handling during priming and subsequent inhalation procedure. METHODS: A Phase II, randomized, double-blind, two-way crossover study (NCT01696071) comparing two daily dosing regimens of tiotropium for 4 weeks, once-daily 5 μg (evening dosing) or twice-daily 2.5 μg (morning and evening dosing), as add-on to maintenance therapy with ICS (400-800 μg budesonide or equivalent) as controller medication. There was no washout between treatment periods. RESULTS: An increase in the area under the curve of the 24-hour forced expiratory volume in 1 second profile from study baseline was observed following once-daily tiotropium 5 μg (217 mL) and twice-daily 2.5 μg (219 mL), with no difference between the two regimens (-2 mL [95% confidence interval: -38, 34]). In a subset of the study population, total tiotropium exposure, expressed as area under the plasma concentration versus time curve over 24 hours, was comparable between dosing regimens. Unexpected tiotropium plasma levels were observed in two patients, possibly because of contamination. CONCLUSIONS: The observed bronchodilator efficacy over 24 hours was similar with once-daily tiotropium 5 μg and twice-daily 2.5 μg as add-on to ICS therapy, supporting the suitability of once-daily dosing to provide sustained improvements in lung function in adults with symptomatic asthma.
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