Safety and efficacy of fluticasone/formoterol combination therapy in adolescent and adult patients with mild-to-moderate asthma: a randomised controlled trial.
BACKGROUND
This study investigated the efficacy and safety of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol; flutiform®), administered twice daily (b.i.d.) via a single aerosol inhaler, compared with its individual components administered separately and placebo, in patients with mild-to-moderate asthma.


METHODS
Patients aged ≥ 12 years were evenly randomised to 12 weeks of treatment with fluticasone/formoterol (100/10 μg b.i.d.), fluticasone (100 μg b.i.d.), formoterol (10 μg b.i.d.), or placebo, in this double-blind, parallel group, multicentre study. The three co-primary endpoints were: a) change in forced expiratory volume in the first second (FEV(1)) from morning pre-dose at baseline to pre-dose at week 12 for the comparison with formoterol; b) change in FEV(1) from morning pre-dose at baseline to 2 hours post-dose at week 12 for the comparison with fluticasone, and c) time to discontinuation due to lack of efficacy from baseline to week 12 for the comparison with placebo. Safety was assessed based on adverse events, clinical laboratory tests and vital sign evaluations.


RESULTS
Statistically significant differences were demonstrated for all the three co-primary endpoints. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in pre-dose FEV(1) compared with formoterol (Least Squares (LS) mean treatment difference: 0.101 L; 95% Confidence Interval (CI): 0.002, 0.199; p = 0.045) and the change in pre-dose compared with 2 hours post-dose FEV(1) versus fluticasone (LS mean treatment difference: 0.200 L; 95% CI: 0.109, 0.292; p < 0.001). The time to discontinuation due to lack of efficacy was significantly longer for patients in the combination therapy group compared with those receiving placebo (p = 0.015). Overall, the results from multiple secondary endpoints assessing lung function, asthma symptoms, and rescue medication use supported the superior efficacy of the combination product compared with fluticasone, formoterol, and placebo. The fluticasone/formoterol combination therapy had a good safety and tolerability profile over the 12 week treatment period.


CONCLUSIONS
Fluticasone/formoterol had a good safety and tolerability profile and showed statistically superior efficacy for the three co-primary endpoints compared to fluticasone, formoterol, and placebo, in adolescents and adults with mild-to-moderate asthma. EudraCT number: 2007-002866-36; US NCT number: NCT00393991.
Asthma and Allergy Associates PC, 2709 North Tejon Street, Colorado Springs, CO, USA. drrnathan@aol.com
Robert A
RA
Nathan
Anthony
A
D'Urzo
Viktor
V
Blazhko
Kirsten
K
Kaiser
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D000068298:Fluticasone; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
D000730:Androstadienes; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068298:Fluticasone; D000068759:Formoterol Fumarate