Safety and tolerability of high-dose budesonide/formoterol via turbuhaler® in Japanese patients with asthma: A randomized, double-blind, crossover, active comparator-controlled, phase III study

Abstract

Background: The use of budesonide/formoterol as both maintenance and reliever therapy in asthma is recommended in many countries; however, there are limited data available for the Asian patient population. Objective: This study aimed to evaluate the short-term safety and tolerability of a fixed high-dose combination of the inhaled corticosteroid budesonide and the long-acting β 2-adrenoceptor agonist formoterol with that of the β 2- agonist terbutaline for acute symptom relief in Japanese adults with persistent asthma who were already receiving a combination of budesonide/formoterol maintenance therapy. Methods: This was a randomized, double-blind, crossover, active comparatorcontrolled, phase III study. Patients aged 1665 years with persistent asthma received either budesonide/formoterol 160 mg/4.5 μg ten inhalations daily for 3 days via Turbuhaler® or terbutaline 0.4 μg ten inhalations daily for 3 days via Turbuhaler®, in addition to budesonide/formoterol 160 μg/4.5 μg one inhalation twice daily as maintenance treatment. After a 7- to 14-day washout period, patients crossed over to receive the other medication for a further 3 days. Adverse events (AEs), clinical laboratory variables, 12-lead electrocardiogram (ECG) and vital signs were assessed throughout. Results: Twenty-five patients (mean age 44.3 years, 40% female) were randomized and received at least one dose of study medication. Overall, 14 AEs were reported in 12 out of 25 patients (48%) during high-dose budesonide/ formoterol therapy and 24 AEs were reported in 14 out of 23 patients (61%) during terbutaline therapy. The majority of AEs were mild in intensity and no serious AEs were reported. The most common AEs were tremor (12%) during budesonide/formoterol therapy and tremor (17%), palpitations (13%), tachycardia (13%) and decreased serum potassium (13%) during terbutaline therapy. There were no clinically significant differences from baseline or between groups in laboratory values, vital signs or ECG recordings. Conclusion: Budesonide/formoterol 160 μg/4.5 mg ten inhalations daily for 3 days in addition to ongoing budesonide/formoterol 160 μg/4.5 mg one inhalation twice daily maintenance therapy was well tolerated in Japanese adults with persistent asthma. © 2012 Adis Data Information BV. All right reserved.