A Dose-Finding Study with the Once-Daily Oral ??2-Agonist Bambuterol in Asian Children with Asthma

Abstract

Objective: The primary objective was to compare the efficacy of two dosages of bambuterol, a once-daily oral bronchodilator, with placebo in Asian children with asthma. The secondary objective was to assess the tolerability of bambuterol in this population. Design: This was a multicentre, randomised, double-blind, placebo-controlled crossover study, with a run-in period of 2 weeks. The study consisted of three treatment periods of 2 weeks each, separated by washout periods of 2 weeks, with 7 clinic visits in total. Setting: Outpatients were recruited from 10 centres in Indonesia, Malaysia, The Philippines, Singapore and Thailand. Patients: Seventy Asian children aged 6 to 12 years (53 boys and 17 girls) with asthma for at least 6 months were randomised to treatment, and 62 patients completed the study. Interventions: During the three treatment periods, patients received either placebo or 5 or 10mg bambuterol tablets once daily for 2 weeks. Morning peak expiratory flow (PEF) was the primary efficacy variable. Secondary efficacy variables were forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diary card data including evening PEF. Results: At baseline, FEV1 predicted was 82.9% and the reversibility was 22.2%. The study results suggest that the change from baseline in both morning and evening PEF recorded on the diary cards on days 4 to 14 of each treatment period was dose dependent, but only the difference in morning PEF between bambuterol 10mg and placebo was statistically significant (9.1 L/min; 95% confidence interval 0.2 to 18.0 L/min). FEV1, FVC, asthma symptom scores and the use of supplementary β2-agonists did not differ significantly between placebo and the two bambuterol treatments. Blood pressure and pulse rate remained consistent throughout the study. The number of spontaneously reported adverse events was similar for the three treatment groups. Conclusions: Bambuterol 10mg once daily is an effective bronchodilator in 6-to 12-year-old Asian children in terms of improvement in morning PEF.