A 12-week open-label, randomized, controlled trial and 24-week extension to assess the efficacy and safety of fluticasone propionate/formoterol in children with asthma

Abstract

Objectives: The present study was conducted to assess the efficacy, safety and tolerability of fluticasone propionate/formoterol fumarate combination therapy (FP/FORM; Flutiform®) compared with fluticasone propionate/salmeterol xinafoate (FP/SAL; Seretide® Evohaler®) in children with asthma. Methods: This was an open-label, randomized, controlled, phase III trial and extension. Patients aged 4–12 years with reversible asthma [% predicted forced expiratory volume in 1 second (FEV1) 60–100%; documented reversibility of ⩾15% in FEV1] were randomized to receive FP/FORM (100/10 µg b.i.d.) or FP/SAL (100/50 µg b.i.d.) for 12 weeks. Eligible patients completing the 12-week core phase entered a 24-week extension phase with FP/FORM (100/10 µg b.i.d.). The primary efficacy endpoint was the change in predose FEV1 from day 0 to day 84. Secondary efficacy endpoints included change in predose to 2-hours postdose FEV1 from day 0 to day 84, peak expiratory flow rate (PEFR), patient-reported outcomes, rescue-medication use and asthma exacerbations. Results: In total, 211 patients were randomized and 210 completed the core phase; of these patients, 208 entered and 205 completed the extension phase of the study. Predose FEV1 increased from day 0 to day 84 [FP/FORM, 182 ml; 95% confidence interval (CI), 127, 236; FP/SAL, 212 ml, 95% CI, 160, 265] and FP/FORM was noninferior to FP/SAL: least squares (LS) mean treatment difference: –0.031 (95% CI, –0.093, 0.031; p = 0.026). Secondary efficacy analyses indicated similar efficacy with both therapies. There were no notable differences observed in the safety and tolerability profile between treatments. No safety concerns were identified with long-term FP/FORM therapy, and there was no evidence of an effect of FP/FORM on plasma cortisol. Conclusions: FP/FORM improved lung function and measures of asthma control with comparable efficacy to FP/SAL, and demonstrated a favourable safety and tolerability profile in children aged 4–12 years.

The comparison of fluticasone propionate/formoterol with fluticasone propionate/salmeterol for paediatric asthma: a meta-analysis of randomized controlled trials

“…Our meta-analysis suggests that FP/FORM and FP/ SAL have comparable lung function, asthma symptom scores and sleep disturbance scores in paediatric asthma. There is a modest increase in mean FEV 1 of 105 ml during the extension phase, predicted FEV 1 remains very stable between day 84 and day 252, suggesting that the increase in FEV 1 may be mainly caused by the growth of children during the 24-week extension phase [16] Total (95% CI) 100.0 0.00 (-0.07, 0.06) Heterogeneity: t 2 = 0.00, c 2 = 0.00, df = 1 (p = 0.99), I 2 = 0%…”

“…Three hundred and fifty-five potentially relevant articles are identified initially. Finally, two full articles and one abstract that meet our inclusion criteria are included in the meta-analysis [16][17][18].…”

“…Among the three studies included here, two studies report FEV 1 , FVC, FEF25, FEF50, FEF75, asthma symptom scores and sleep disturbance scores [16,17], and three studies report adverse events [16][17][18]. Jadad scores of the three included studies vary from 3 to 5, and all three studies are considered to be high-quality ones according to quality assessment.…”

“…Flutiform®, fluticasone propionate and formoterol fumarate (FP/FORM) combination therapy has revealed the efficacy for adults and/or adolescents with mild to severe asthma, and has been approved for use in over 30 countries [11][12][13][14][15]. An open-label, randomized, controlled, phase III trial involving 211 patients compares FP/FORM with FP/SAL in paediatric asthmatic patients, and the results show that they have comparable lung function improvement and asthma control [16].…”

“…Recently, several studies have reported FP/FORM versus FP/SAL for paediatric asthma have been published, but their efficacy has not been well established [16][17][18].…”