title: 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 β2-adrenoceptor agonist formoterol with that of the β2-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 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Ibarakihigashi National Hospital, 825 Terunuma Tokaimura Naka-gun, Ibaraki, 319-1113, Japan. takefumisaito@yahoo.co.jp.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Bioiatric Center, Research Center for Clinical Pharmacology, Kitasato University, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hasunuma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D000068759:Formoterol Fumarate / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D019819:Budesonide; D000068759:Formoterol Fumarate