Clinical Drug Investigation

, Volume 32, Issue 1, pp 51–61 | Cite as

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
Original Research Article


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.

Conclusion: 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.



We thank all patients who participated in the study.

The study was funded by AstraZeneca, Lund, Sweden. AstraZeneca was involved in the design and conduct of the study; collection, analysis and interpretation of the data in the study report; and the preparation and review of the manuscript. The interpretation of the data presented in this article represents the views of the authors, as does the decision to submit the article to Clinical Drug Investigation. Editorial assistance was provided by Ian Wright, Wright Medical Communications Ltd, Hartford, UK, who prepared the outline and initial and subsequent drafts of the article following input and feedback from the authors. This support was funded by AstraZeneca.

TS has received lecture fees from Novartis Pharma KK, Astellas Pharma Inc., MSD KK, Shionogi & Co. Ltd and Dainippon Sumitomo Pharma Co. Ltd. TH has received lecture fees from Kyorin Pharmaceutical Co. Ltd and Daiichi Sankyo Co. Ltd. There are no other potential conflicts of interest.


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© Adis Data Information BV 2012

Authors and Affiliations

  1. 1.Department of Respiratory MedicineNational Hospital Organization Ibarakihigashi National HospitalIbarakiJapan
  2. 2.Bioiatric Center, Research Center for Clinical PharmacologyKitasato UniversityTokyoJapan

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