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

• Published in: Clinical drug investigation Vol. 32; no. 1; p. 51
• Main Authors: Saito, Takefumi, Hasunuma, Tomoko
• Format: Journal Article
• Language: English
• Published: New Zealand 01.01.2012
• Subjects: Adolescent; Adult; Aged; Asthma - drug therapy; Bronchodilator Agents - administration & dosage; Budesonide - administration & dosage; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Formoterol Fumarate - administration & dosage; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Young Adult
• ISSN: 1179-1918

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. 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 -adrenoceptor agonist formoterol with that of the β -agonist terbutaline for acute symptom relief in Japanese adults with persistent asthma who were already receiving a combination of budesonide/formoterol maintenance therapy. 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 mg/4.5 mg ten inhalations daily for 3 days via Turbuhaler® or terbutaline 0.4 mg ten inhalations daily for 3 days via Turbuhaler®, in addition to budesonide/formoterol 160 μg/4.5 mg 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. 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. Budesonide/formoterol 160 μg/4.5 mg ten inhalations daily for 3 days in addition to ongoing budesonide/formoterol 160 μg/4.5 μg one inhalation twice daily maintenance therapy was well tolerated in Japanese adults with persistent asthma.