Safety and Tolerability of High-Dose Budesonide/Formoterol via Turbuhaler(R) in Japanese Patients with Asthma: A Randomized, Double-Blind, Crossover, Active Comparator-Controlled, Phase III Study.

Author(s): Saito T, Hasunuma T

Affiliation(s): Department of Respiratory Medicine, National Hospital Organization Ibarakihigashi National Hospital, Ibaraki, Japan.

Publication date & source: 2012-01-01, Clin Drug Investig., 32(1):51-61.

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 beta(2)-adrenoceptor agonist formoterol with that of the beta(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 comparator-controlled, phase III study. Patients aged 16-65 years with persistent asthma received either budesonide/formoterol 160 mug/4.5 mug ten inhalations daily for 3 days via Turbuhaler(R) or terbutaline 0.4 mg ten inhalations daily for 3 days via Turbuhaler(R), in addition to budesonide/formoterol 160 mug/4.5 mug 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 mug/4.5 mug ten inhalations daily for 3 days in addition to ongoing budesonide/formoterol 160 mug/4.5 mug one inhalation twice daily maintenance therapy was well tolerated in Japanese adults with persistent asthma. Trial Registration: Clinicaltrials.gov identifier: NCT00837967; AstraZeneca study code: D589LC00003.