Randomized, dose-ranging study of a fluticasone propionate multidose dry powder inhaler in adolescents and adults with uncontrolled asthma not previously treated with inhaled corticosteroids.
A novel, inhalation-driven, multidose dry powder inhaler (MDPI) eliminates the need to coordinate actuation with inhalation. To characterize dose response, efficacy, and safety of fluticasone propionate (Fp) MDPI, a dose-ranging study was conducted with placebo and active comparators.



This 12-week, double-blind, parallel-group study randomized patients aged ≥12 years with uncontrolled persistent asthma not previously treated with inhaled corticosteroid therapy (N = 622) to twice-daily treatment with Fp MDPI (12.5, 25, 50, or 100 µg), placebo MDPI, or open-label Fp dry powder inhaler (DPI) 100 µg. The primary efficacy endpoint was change from baseline over 12 weeks in trough (morning pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV1). Blood samples were collected from a patient subset to evaluate pharmacokinetics. Adverse events were monitored.



Fp MDPI 25, 50, and 100 µg significantly improved change from baseline in trough FEV1over 12 weeks compared with placebo (p < 0.01). There were no substantial differences in FEV1change from baseline over 12 weeks between any Fp MDPI dose and Fp DPI 100 µg. Maximum observed concentration (Cmax) of Fp increased with increasing Fp MDPI doses; time of Cmaxwas similar across doses and treatments. Systemic exposures for Fp MDPI 25 and 50 µg were lower than that for Fp DPI 100 µg. The safety profile of Fp MDPI was consistent with that of Fp DPI.



In this study, Fp MDPI 25 and 50 µg provided comparable efficacy and safety to Fp DPI 100 µg, with lower systemic exposure.
a Clinical Research Institute of Southern Oregon, PC, and Allergy & Asthma Center of Southern Oregon, PC , Medford , OR , USA.
Edward M
EM
Kerwin
b Teva Pharmaceuticals , Frazer , PA , USA.
Michael
M
Gillespie
b Teva Pharmaceuticals , Frazer , PA , USA.
Sharon
S
Song
b Teva Pharmaceuticals , Frazer , PA , USA.
Jonathan
J
Steinfeld
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D058995:Dry Powder Inhalers; D005260:Female; D000068298:Fluticasone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D055815:Young Adult
D001993:Bronchodilator Agents; D000068298:Fluticasone
Inhaled corticosteroid; dose response; efficacy; inhalation-driven; persistent asthma; pharmacokinetics; safety