The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD.
OBJECTIVE
To compare the efficacy and safety of the inhaled corticosteroid fluticasone propionate (FP) and the inhaled long-acting beta(2)-agonist salmeterol (SM), when administered together in a single device (Diskus; GlaxoSmithKline, Inc; Research Triangle Park, NC), with that of placebo and the individual agents alone in patients with COPD.


METHODS
Randomized, double-blind, multicenter, placebo-controlled study.


METHODS
Seventy-six investigative sites in the United States.


METHODS
Seven hundred twenty-three patients > or =40 years of age with COPD and a mean baseline FEV(1) of 42% predicted.


METHODS
FP (250 microg), SM (50 microg), FP plus SM combined in a single inhaler (FSC), or placebo administered twice daily through the Diskus device for 24 weeks.


METHODS
Primary efficacy measures were morning predose (ie, trough FEV(1)) for FSC compared with SM and 2-h postdose FEV(1) for FSC compared with FP. Other efficacy measures were as follows: morning peak expiratory flow rate (PEF); transition dyspnea index; chronic respiratory disease questionnaire; chronic bronchitis symptom questionnaire; exacerbations; and other symptomatic measures.


RESULTS
At Endpoint (ie, the last on-treatment, post-baseline assessment), treatment with FSC significantly (p < or = 0.012) increased the morning predose FEV(1) (165 mL) compared with SM (91 mL) and placebo (1 mL), and significantly (p < or = 0.001) increased the 2-h postdose FEV(1) (281 mL) compared with FP (147 mL) and placebo (58 mL). Improvements in lung function with FSC compared with FP and SM, and with FP and SM compared with placebo, as measured by the average daily morning PEF, was observed within approximately 24 h after the initiation of treatment, indicating an early onset of effect (p < or = 0.034). Compared with placebo, FSC significantly improved dyspnea, quality of life, and symptoms of chronic bronchitis. The incidence of adverse effects (except for an increase in oral candidiasis with FSC and FP) were similar among the treatment groups.


CONCLUSIONS
Treatment with FSC (FP, 250 microg, and SM, 50 microg) twice daily substantially improved morning lung function and sustained these improvements for over a period of 24 weeks compared with FP or SM treatment alone in patients with COPD, with no additional safety concerns for the combination treatment vs that with the individual components.
Hanania
Nicola A
NA
Baylor College of Medicine, Pulmonary/Critical Care, Ben Taub General Hospital, 1504 Taub Loop, Houston, TX 77030, USA. hanania@bcm.tmc.edu
Darken
Patrick
P
Horstman
Donald
D
Reisner
Colin
C
Lee
Benjamin
B
Davis
Suzanne
S
Shah
Tushar
T
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy*; D000068299:Salmeterol Xinafoate; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol