Adult and Adolescent Patients Aged 12 Years and Older: In clinical trials comparing ADVAIR DISKUS with its individual components, improvements in most efficacy endpoints were greater with ADVAIR DISKUS than with the use of either fluticasone propionate or salmeterol alone. In addition, clinical trials showed similar results between ADVAIR DISKUS and the concurrent use of fluticasone propionate plus salmeterol at corresponding doses from separate inhalers. 

Studies Comparing ADVAIR DISKUS to Fluticasone Propionate Alone or Salmeterol Alone: Three (3) double-blind, parallel-group clinical trials were conducted with ADVAIR DISKUS in 1,208 adolescent and adult patients (≥12 years, baseline FEV1 63% to 72% of predicted normal) with asthma that was not optimally controlled on their current therapy. All treatments were inhalation powders given as 1 inhalation from the DISKUS device twice daily, and other maintenance therapies were discontinued.

Study 1: Clinical Trial With ADVAIR DISKUS 100/50: This placebo-controlled, 12-week, US study compared ADVAIR DISKUS 100/50 with its individual components, fluticasone propionate 100 mcg and salmeterol 50 mcg. The study was stratified according to baseline asthma maintenance therapy; patients were using either inhaled corticosteroids (N = 250) (daily doses of beclomethasone dipropionate 252 to 420 mcg; flunisolide 1,000 mcg; fluticasone propionate inhalation aerosol 176 mcg; or triamcinolone acetonide 600 to 1,000 mcg) or salmeterol (N = 106). Baseline FEV1 measurements were similar across treatments: ADVAIR DISKUS 100/50, 2.17 L; fluticasone propionate 100 mcg, 2.11 L; salmeterol, 2.13 L; and placebo, 2.15 L.

Predefined withdrawal criteria for lack of efficacy, an indicator of worsening asthma, were utilized for this placebo-controlled study. Worsening asthma was defined as a clinically important decrease in FEV1 or PEF, increase in use of VENTOLIN® (albuterol, USP) Inhalation Aerosol, increase in night awakenings due to asthma, emergency intervention or hospitalization due to asthma, or requirement for asthma medication not allowed by the protocol. As shown in Table 4, statistically significantly fewer patients receiving ADVAIR DISKUS 100/50 were withdrawn due to worsening asthma compared with fluticasone propionate, salmeterol, and placebo.

The FEV1 results are displayed in Figure 2. Because this trial used predetermined criteria for worsening asthma, which caused more patients in the placebo group to be withdrawn, FEV1 results at Endpoint (last available FEV1 result) are also provided. Patients receiving ADVAIR DISKUS 100/50 had significantly greater improvements in FEV1 (0.51 L, 25%) compared with fluticasone propionate 100 mcg (0.28 L, 15%), salmeterol (0.11 L, 5%), and placebo (0.01 L, 1%). These improvements in FEV1 with ADVAIR DISKUS were achieved regardless of baseline asthma maintenance therapy (inhaled corticosteroids or salmeterol).

Figure 2. Mean Percent Change From Baseline in FEV1 in Patients With Asthma Previously Treated With Either Inhaled Corticosteroids or Salmeterol (Study 1)

The effect of ADVAIR DISKUS 100/50 on morning and evening PEF endpoints is shown in Table 5.

aChange from baseline = change from baseline at Endpoint (last available data).

The subjective impact of asthma on patients’ perception of health was evaluated through use of an instrument called the Asthma Quality of Life Questionnaire (AQLQ) (based on a 7-point scale where 1 = maximum impairment and 7 = none). Patients receiving ADVAIR DISKUS 100/50 had clinically meaningful improvements in overall asthma-specific quality of life as defined by a difference between groups of ≥0.5 points in change from baseline AQLQ scores (difference in AQLQ score of 1.25 compared with placebo).

Study 2: Clinical Trial With ADVAIR DISKUS 250/50: This placebo-controlled, 12-week, US study compared ADVAIR DISKUS 250/50 with its individual components, fluticasone propionate 250 mcg and salmeterol 50 mcg, in 349 patients with asthma using inhaled corticosteroids (daily doses of beclomethasone dipropionate 462 to 672 mcg; flunisolide 1,250 to 2,000 mcg; fluticasone propionate inhalation aerosol 440 mcg; or triamcinolone acetonide 1,100 to 1,600 mcg). Baseline FEV1 measurements were similar across treatments: ADVAIR DISKUS 250/50, 2.23 L; fluticasone propionate 250 mcg, 2.12 L; salmeterol, 2.20 L; and placebo, 2.19 L.

Efficacy results in this study were similar to those observed in Study 1. Patients receiving ADVAIR DISKUS 250/50 had significantly greater improvements in FEV1 (0.48 L, 23%) compared with fluticasone propionate 250 mcg (0.25 L, 13%), salmeterol (0.05 L, 4%), and placebo (decrease of 0.11 L, decrease of 5%). Statistically significantly fewer patients receiving ADVAIR DISKUS 250/50 were withdrawn from this study for worsening asthma (4%) compared with fluticasone propionate (22%), salmeterol (38%), and placebo (62%). In addition, ADVAIR DISKUS 250/50 was superior to fluticasone propionate, salmeterol, and placebo for improvements in morning and evening PEF. Patients receiving ADVAIR DISKUS 250/50 also had clinically meaningful improvements in overall asthma-specific quality of life as described in Study 1 (difference in AQLQ score of 1.29 compared with placebo).

Study 3: Clinical Trial With ADVAIR DISKUS 500/50: This 28-week, non-US study compared ADVAIR DISKUS 500/50 with fluticasone propionate 500 mcg alone and concurrent therapy (salmeterol 50 mcg plus fluticasone propionate 500 mcg administered from separate inhalers) twice daily in 503 patients with asthma using inhaled corticosteroids (daily doses of beclomethasone dipropionate 1,260 to 1,680 mcg; budesonide 1,500 to 2,000 mcg; flunisolide 1,500 to 2,000 mcg; or fluticasone propionate inhalation aerosol 660 to 880 mcg [750 to 1,000 mcg inhalation powder]). The primary efficacy parameter, morning PEF, was collected daily for the first 12 weeks of the study. The primary purpose of weeks 13 to 28 was to collect safety data.

Baseline PEF measurements were similar across treatments: ADVAIR DISKUS 500/50, 359 L/min; fluticasone propionate 500 mcg, 351 L/min; and concurrent therapy, 345 L/min. Morning PEF improved significantly with ADVAIR DISKUS 500/50 compared with fluticasone propionate 500 mcg over the 12-week treatment period. Improvements in morning PEF observed with ADVAIR DISKUS 500/50 were similar to improvements observed with concurrent therapy.

Onset of Action and Progression of Improvement in Asthma Control: The onset of action and progression of improvement in asthma control were evaluated in the 2 placebo-controlled US trials. Following the first dose, the median time to onset of clinically significant bronchodilatation (≥15% improvement in FEV1) in most patients was seen within 30 to 60 minutes. Maximum improvement in FEV1 generally occurred within 3 hours, and clinically significant improvement was maintained for 12 hours (see Figure 3). Following the initial dose, predose FEV1 relative to Day 1 baseline improved markedly over the first week of treatment and continued to improve over the 12 weeks of treatment in both studies. No diminution in the 12-hour bronchodilator effect was observed with either ADVAIR DISKUS 100/50 (Figures 3 and 4) or ADVAIR DISKUS 250/50 as assessed by FEV1 following 12 weeks of therapy.

  * First Treatment Day



Figure 3. Percent Change in Serial 12-hour FEV1 in Patients With Asthma Previously Using Either Inhaled Corticosteroids or Salmeterol (Study 1)

  * Last Treatment Day (Week 12)



Figure 4. Percent Change in Serial 12-hour FEV1 in Patients With Asthma Previously Using Either Inhaled Corticosteroids or Salmeterol (Study 1)

Reduction in asthma symptoms, use of rescue VENTOLIN Inhalation Aerosol, and improvement in morning and evening PEF also occurred within the first day of treatment with ADVAIR DISKUS, and continued to improve over the 12 weeks of therapy in both studies.

Pediatric Patients: In a 12-week US study, ADVAIR DISKUS 100/50 twice daily was compared with fluticasone propionate inhalation powder 100 mcg twice daily in 203 children with asthma aged 4 to 11 years. At study entry, the children were symptomatic on low doses of inhaled corticosteroids (beclomethasone dipropionate 252 to 336 mcg/day; budesonide 200 to 400 mcg/day; flunisolide 1,000 mcg/day; triamcinolone acetonide 600 to 1,000 mcg/day; or fluticasone propionate 88 to 250 mcg/day). The primary objective of this study was to determine the safety of ADVAIR DISKUS 100/50 compared with fluticasone propionate inhalation powder 100 mcg in this age-group; however, the study also included secondary efficacy measures of pulmonary function. Morning predose FEV1 was obtained at baseline and Endpoint (last available FEV1 result) in children aged 6 to 11 years. In patients receiving ADVAIR DISKUS 100/50, FEV1 increased from 1.70 L at baseline (N = 79) to 1.88 L at Endpoint (N = 69) compared with an increase from 1.65 L at baseline (N = 83) to 1.77 L at Endpoint (N = 75) in patients receiving fluticasone propionate 100 mcg.

The findings of this study, along with extrapolation of efficacy data from patients aged 12 years and older, support the overall conclusion that ADVAIR DISKUS 100/50 is efficacious in the treatment of asthma in patients aged 4 to 11 years.