Assessment of the efficacy and safety of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler and a multi-dose inhaler in patients with asthma.
In developing countries, there is a need for access to affordable inhaled respiratory medicines. This study tested the clinical non-inferiority of fluticasone propionate/salmeterol combination (FSC) 50/250 μg Rotacaps®/Rotahaler®compared with FSC 50/250 μg Diskus®.



A multi-centre, randomised, double-blind, double-dummy study evaluated 12 weeks, twice daily treatment of FSC 50/250 μg administered using Rotacaps/Rotahaler or Diskus inhaler in a crossover design in patients with asthma (pre-bronchodilator forced expiratory volume in 1 s (FEV1) 40%-85% of predicted, FEV1reversibility ≥12%, prior stable dose with inhaled corticosteroid (ICS) or ICS/long acting beta-agonist). The primary efficacy endpoint, change from baseline in trough morning FEV1at Day 85, was analysed using a model for repeated measures analysis. The pre-defined criterion for non-inferiority was the lower limit of the CI (0.025, one-sided significance level) for the treatment difference (Rotacaps/Rotahaler-Diskus) in least squares (LS) mean change from baseline, being greater than -125 mL. Secondary endpoints included serial FEV1measurements, morning peak expiratory flow (PEF), rescue medication use, day- and night-time asthma symptoms, Asthma Control Test (ACT) scores, and serial cortisol measured over 12 h (area under the curve (AUC0-12)).



Treatment with FSC 50/250 μg via Rotacaps/Rotahaler or Diskus resulted in a similar LS mean increase from baseline in trough FEV1at Day 85 (231 mL and 203 mL respectively). The difference in the model-adjusted LS mean change was 28 mL (95% CI -24 mL, 80 mL), fulfilling the criterion for non-inferiority. Data for all secondary endpoints were similar for the two treatments, supporting the primary endpoint findings. Both treatments were well tolerated and demonstrated similar safety profiles.



This study demonstrated the clinical non-inferiority of FSC 50/250 μg when administered using Rotacaps/Rotahaler compared with administration using Diskus in patients with asthma, and suggests there is no difference in the risk:benefit profile between the two FSC inhalers.
Respiratory Therapy Area Unit, GlaxoSmithKline, Stockley Park, Uxbridge, UK. Electronic address: robert.h.chan@gsk.com.
Robert
R
Chan
Respiratory Therapy Area Unit, GlaxoSmithKline, Stockley Park, Uxbridge, UK.
Ana R
AR
Sousa
Clinical Statistics, GlaxoSmithKline, Stockley Park, Uxbridge, UK.
Stephen
S
Mallett
Respiratory Therapy Area Unit, GlaxoSmithKline, Stockley Park, Uxbridge, UK.
Peter
P
Hynds
Respiratory Therapy Area Unit, GlaxoSmithKline, Stockley Park, Uxbridge, UK.
Farshid
F
Homayoun-Valiani
Value, Evidence and Outcomes, GlaxoSmithKline, Stockley Park, Uxbridge, UK.
Maggie
M
Tabberer
Clinical Pharmacology Modeling Simulation, GlaxoSmithKline, Research Triangle Park, NC, USA.
Rashmi
R
Mehta
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010366:Peak Expiratory Flow Rate; D016896:Treatment Outcome; D055815:Young Adult
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D000068297:Fluticasone-Salmeterol Drug Combination
Asthma; Fluticasone propionate; Multi-dose inhaler; Non-inferiority; Salmeterol; Unit-dose inhaler