A one-week dose-ranging study of inhaled salmeterol in children with asthma

This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma. A total of 243 children, aged 4-11 years, with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21 mu g and 42 mu g administered via metered-dose inhaler (MDI) twice daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could be continued during the study, but theophylline and oral beta-agonists were not allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of treatment; morning and evening PEFR were recorded each day prior to inhalation of the study drug. Safety was assessed by monitoring adverse events, clinical laboratory values, vital signs, electrocardiogram (EGG), and 24-hr ECG (Holter) monitoring. Both the 21-mu g and 42-mu g doses of salmeterol produced significantly greater bronchodilation, as measured by 12-hr serial forced expiratory volume in 1 sec (FEV(1)) (p less than or equal to 0.02) and PEFR (p less than or equal to 0.001), than did placebo on days 1 and 8. A small dose-response was observed, with the 42-mu g dosage producing consistently higher serial FEV(1) and PEFR than did the 21-mu g dosage, although the differences were not statistically significant. Morning and evening PEFR increased significantly (p less than or equal to 0.008) with both dosages of salmeterol compared with placebo. Twelve patients (5%) experienced potentially drug-related adverse events, with headache (4% in each salmeterol group) being the most common. There were no clinically significant changes in heart rate as measured by Holter monitoring, ECGs, vital signs, or clinical laboratory values following treatment with either dose of salmeterol. Salmeterol 21 mu g or 42 mu g twice daily was effective in producing bronchodilation in children aged 4-11 years, and both dosages had good safety profiles. Patients treated with salmeterol 42 mu g twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 mu g.