title: Clinical equivalence of salmeterol/fluticasone propionate in combination (50/100 microg twice daily) when administered via a chlorofluorocarbon-free metered dose inhaler or dry powder inhaler to patients with mild-to-moderate asthma.
abstract: This multi-centre, randomized, double-blind, double-dummy, parallel-group study was designed to investigate the hypothesis of equivalent efficacy and comparable safety of two inhaled presentations of salmeterol/fluticasone propionate combination product (SALM/FP) 50/100 microg administered twice daily to patients with mild-to-moderate asthma for 12 weeks. The delivery systems were a 25/50 microg strength hydrofluoroalkane (HFA) metered-dose inhaler (MDI) and a Diskus inhaler (50/100 microg strength). A third group received FP 100 microg twice daily via a chlorofluorocarbon MDI (50 microg strength). A total of 497 patients aged 11-79 years with reversible airways obstruction who were symptomatic on inhaled corticosteroid (ICS) therapy and had room for improvement in lung function were randomized to treatment in a double-blind, parallel-group design (SALM/FP MDI: n=165; SALM/FP Diskus: n=167; FP MDI: n=165) for 12 weeks. A total of 383 patients completed the study according to the protocol. According to the primary efficacy variable, increase in mean morning PEF over weeks 1-12, the two inhaled presentations of SALM/FP were clinically equivalent (adjusted mean increases 43 and 46 l min(-1); treatment difference 3 l min(-1); 95% confidence interval: -6 to 11 l min(-1)). Equivalence was also demonstrated by all secondary efficacy measures. The SALM/FP MDI was significantly superior to the FP MDI for increase in mean morning PEF (treatment difference 19 l min(-1); P<0.001) and for all secondary measures except FEV1 and symptom-free nights. There was no significant difference between the groups with respect to adverse events and serum cortisol levels. These results demonstrate that the SALM/FP 25/50 microg HFA MDI (two inhalations twice daily) is clinically equivalent to the SALM/FP 50/100 microg Diskus (one inhalation twice daily). Patients switching to SALM/FP from other MDI-based asthma treatments may now do so without a change of delivery device.
authors.affiliation: UCT Lung Institute, Groote Schuur, Cape Town, South Africa. ebateman@uctgsh1.uct.ac.za
authors.forename: E D
authors.initials: ED
authors.lastname: Bateman
authors.forename: V
authors.initials: V
authors.lastname: Silins
authors.forename: M
authors.initials: M
authors.lastname: Bogolubov
mesh_terms: D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000704:Analysis of Variance; D000730:Androstadienes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005500:Follow-Up Studies; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D000068299:Salmeterol Xinafoate; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol