OBJECTIVES: This study investigated the efficacy and tolerability of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol)*, administered twice daily (BID) via a single aerosol inhaler, compared with fluticasone propionate (fluticasone) or formoterol fumarate (formoterol) administered alone, in patients with mild to moderate asthma. METHODS:Patients aged ≥12 years were evenly randomized to 12 weeks of treatment with fluticasone/formoterol (100/10 µg BID), fluticasone (100 µg BID), or formoterol (10 µg BID), in this multicenter, double-blind, parallel-group, study. The 2 coprimary end points were: (1) change in forced expiratory volume in 1 second (FEV(1)) from morning predose at baseline to predose at week 12 for the comparison of the combination product with formoterol alone; and (2) change in FEV(1) from morning predose at baseline to 2 hours postdose at week 12 for the comparison of the combination product with fluticasone alone. The secondary objective was to demonstrate the efficacy of fluticasone/formoterol using other pulmonary function tests and clinical end points. Tolerability was assessed based on adverse events, clinical laboratory tests and vital sign evaluations. RESULTS: Statistically significant differences were demonstrated for the 2 coprimary end points. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in predose FEV(1) compared with formoterol (least squares [LS] mean treatment difference, 0.118 L [95% CI, 0.034-0.201; P = 0.006]) and the change in predose compared with 2 hours postdose FEV(1) versus fluticasone (LS mean treatment difference, 0.122 L [95% CI, 0.040-0.204; P = 0.004]). Statistical analyses of the secondary efficacy endpoints revealed that evaluations of lung function, asthma exacerbations, asthma symptoms, rescue medication use and asthma control were supportive overall of the superior efficacy of fluticasone/formoterol combination therapy compared with its individual components; were supportive overall of the efficacy of fluticasone/formoterol combination therapy compared with its individual components. Since the secondary endpoints were analyzed using the sequential gatekeeper approach, only the mean change from baseline to final week in morning peak expiratory flow rate between the combination-therapy and formoterol groups returned statistically significant results (least squares mean difference, 20.05 [95% CI, 7.631-32.472; P = 0.002]). The fluticasone/formoterol combination therapy had a good tolerability profile over the 12-week treatment period. CONCLUSIONS:Fluticasone/formoterol had a good tolerability profile and showed statistically superior efficacy for the two co-primary endpoints compared to fluticasone or formoterol, in adolescents and adults with mild to moderate asthma. ClinicalTrials.gov identifier: NCT00394199.
RCT Entities:
OBJECTIVES: This study investigated the efficacy and tolerability of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol)*, administered twice daily (BID) via a single aerosol inhaler, compared with fluticasone propionate (fluticasone) or formoterol fumarate (formoterol) administered alone, in patients with mild to moderate asthma. METHODS:Patients aged ≥12 years were evenly randomized to 12 weeks of treatment with fluticasone/formoterol (100/10 µg BID), fluticasone (100 µg BID), or formoterol (10 µg BID), in this multicenter, double-blind, parallel-group, study. The 2 coprimary end points were: (1) change in forced expiratory volume in 1 second (FEV(1)) from morning predose at baseline to predose at week 12 for the comparison of the combination product with formoterol alone; and (2) change in FEV(1) from morning predose at baseline to 2 hours postdose at week 12 for the comparison of the combination product with fluticasone alone. The secondary objective was to demonstrate the efficacy of fluticasone/formoterol using other pulmonary function tests and clinical end points. Tolerability was assessed based on adverse events, clinical laboratory tests and vital sign evaluations. RESULTS: Statistically significant differences were demonstrated for the 2 coprimary end points. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in predose FEV(1) compared with formoterol (least squares [LS] mean treatment difference, 0.118 L [95% CI, 0.034-0.201; P = 0.006]) and the change in predose compared with 2 hours postdose FEV(1) versus fluticasone (LS mean treatment difference, 0.122 L [95% CI, 0.040-0.204; P = 0.004]). Statistical analyses of the secondary efficacy endpoints revealed that evaluations of lung function, asthma exacerbations, asthma symptoms, rescue medication use and asthma control were supportive overall of the superior efficacy of fluticasone/formoterol combination therapy compared with its individual components; were supportive overall of the efficacy of fluticasone/formoterol combination therapy compared with its individual components. Since the secondary endpoints were analyzed using the sequential gatekeeper approach, only the mean change from baseline to final week in morning peak expiratory flow rate between the combination-therapy and formoterol groups returned statistically significant results (least squares mean difference, 20.05 [95% CI, 7.631-32.472; P = 0.002]). The fluticasone/formoterol combination therapy had a good tolerability profile over the 12-week treatment period. CONCLUSIONS:Fluticasone/formoterol had a good tolerability profile and showed statistically superior efficacy for the two co-primary endpoints compared to fluticasone or formoterol, in adolescents and adults with mild to moderate asthma. ClinicalTrials.gov identifier: NCT00394199.