A 12-Week Dose-Ranging Study of Fluticasone Propionate Powder in the Treatment of Asthma

Abstract

Fluticasone propionate (FP) administered via metered-dose inhaler is a potent corticosteroid effective in the treatment of asthma. To evaluate the efficacy and safety of FP powder administered via a breath-activated inhaler (Diskhaler), a multicenter, double-blind, randomized, placebo-controlled, parallel-group study was conducted in adolescent and adult patients (n = 331) with mild-to-moderate asthma previously treated with beta 2-agonist therapy alone. Patients received FP powder 50, 100, or 250 micrograms or placebo twice daily for 12 weeks. FP-treated patients compared with placebo-treated patients had significantly (p < 0.001) greater improvements in morning predose forced expiratory volume in 1 sec (21-22% increase vs. 9%). Improvement in morning peak flow rate were also significantly (p < 0.001) greater with FP than with placebo (8-10% increase vs. 2% increase). There was also a significant overall treatment difference in the frequency of inhaled albuterol use (p < 0.001) and number of nighttime awakenings due to asthma (p = 0.005). There were no statistically significant difference among the FP treatment groups in any outcome measure. Physicians' global assessments also indicated significant (p < 0.001) differences in efficacy, with 67-74% of FP-treated patients rated as having "effective" or "very effective" treatment compared with 41% of placebo-treated patients. Significant beneficial effects of FP were observed in lung function and diary card parameters after just 1 week of treatment. Adverse events were similar across treatment groups and primarily related to local irritation. Effect on hypothalamic-pituitary-adrenal axis function was minimal. In summary, all three dosages of inhaled FP powder were well tolerated and improved various asthma-related variables. Improvements in pulmonary function, beyond those achieved with beta 2-agonist therapy alone, were maintained for the duration of the 12-week study.

Low- and high-dose fluticasone propionate in asthma; effects during and after treatment

“…Overall, these findings indicate that dose/response effects of FP on usual measures of asthma control are not easy to demonstrate. These findings are consistent with those reported previously in other studies [13,14,16]; only when large numbers of subjects are studied is it possible to find a dose/ response effect of inhaled corticosteroids on FEV1 [19,25,26].…”

Efficacy and Safety of Inhaled Corticosteroids

“…Similar results were found in three randomized, doubleblind, parallel group studies, each including over 300 adults with mild to moderate asthma (170)(171)(172). Significant differences were seen between the effects of placebo and those of 50 g/d, 200 g/d, and 1,000 g/d FP pMDI (170), between placebo and 100 g/d, 200 g/d, and 500 g/d (Diskhaler) (171), and between placebo and 200 g/d, 500 g/d, and 1,000 g/d (pMDI).…”

“…Significant differences were seen between the effects of placebo and those of 50 g/d, 200 g/d, and 1,000 g/d FP pMDI (170), between placebo and 100 g/d, 200 g/d, and 500 g/d (Diskhaler) (171), and between placebo and 200 g/d, 500 g/d, and 1,000 g/d (pMDI). Once again, however, no significant differences were seen between the effects of the different doses of FP (although there was a nonsignificant trend toward greater efficacy of the higher doses in two of the three studies).…”

Inhaled fluticasone propionate and adrenal effects in adult asthma: systematic review and meta-analysis

“…Five studies met the criteria for inclusion in this analysis (table 1) [19][20][21][22], of which two were published together [20]. In total, 732 adolescents and adults with asthma were included in the studies.…”

“…The doses of FP ranged 100-2,000 mg?day -1 , with three studies including a prednisone treatment arm [19][20][21]. FP was administered via metered dose inhaler (MDI) in two studies [19,21], and Diskhaler in three studies [20,22]. The studies were of 4-12 weeks' duration.…”