Effectiveness and tolerability of zafirlukast for the treatment of asthma in children.
OBJECTIVE
This study was undertaken to examine the dose-response relationship of zafirlukast (5 to 40 mg BID) and to assess the efficacy and tolerability of the 10-mg BID dose in school-aged children with mild to moderate asthma.


BACKGROUND
The efficacy and tolerability of zafirlukast, an oral leukotriene-receptor antagonist, has been demonstrated in adolescents and adults aged > or = 12 years.


METHODS
Data from 2 placebo-controlled, parallel-group, multicenter trials (trial 1, 4-week double-blind; trial 2, 6-week double-blind) were integrated. Children aged 5 to 11 years were randomly assigned to receive zafirlukast 5 mg BID (n = 99), 10 mg BID (n = 205), 20 mg BID (n = 105), 40 mg BID (n = 99), or placebo (n = 206). The primary outcome was change from baseline in forced expiratory volume in 1 second (FEV1) expressed as percent of predicted normal. Secondary outcomes were FEV1 (L), morning and evening peak expiratory flow, peak flow variability, short-acting beta2-agonist use, asthma episode score, and nights awakened by asthma.


RESULTS
Mean baseline FEV1 was 76.5% of predicted. The greatest improvements were generally seen with zafirlukast 5 mg BID or 10 mg BID, with no additional clinically significant benefits seen at higher doses. The pooled data analysis showed that 10 mg BID compared with placebo significantly improved (P < 0.045) all efficacy outcomes except asthma-episode score and nights awakened with asthma. However, in the subset of children who had > or = 1 night awakened per week at baseline (zafirlukast 10 mg BID = 78; placebo = 86), 10 mg BID significantly reduced nights awakened (P = 0.009) (mean difference from placebo at end point = -0.81 night/wk). All zafirlukast doses were well tolerated and had tolerability profiles that were clinically indistinguishable from placebo.


CONCLUSIONS
These results support the effectiveness and tolerability of the 10-mg BID dose of zafirlukast for the prophylaxis and chronic treatment of mild to moderate asthma in children.
Pearlman
D S
DS
Clinical Research Centers of Colorado, PC, Aurora 80012, USA. dspearlman@aol.com
Lampl
K L
KL
Dowling
P J
PJ
Miller
C J
CJ
Bonuccelli
C M
CM
D000293:Adolescent; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007211:Indoles; D048448:Phenylcarbamates; D010919:Placebos; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*
D018927:Anti-Asthmatic Agents; D007211:Indoles; D048448:Phenylcarbamates; D010919:Placebos; D013449:Sulfonamides; D014105:Tosyl Compounds; C062735:zafirlukast