Trial 5 randomized a total of 1525 patients (765 on DALIRESP) and Trial 6 randomized a total of 1571 patients (772 on DALIRESP). In both trials, DALIRESP 500 mcg once daily demonstrated a significant reduction in the rate of moderate or severe exacerbations compared to placebo (Table 2). These two trials provide the evidence to support the use of DALIRESP for the reduction of COPD exacerbations.

Table 2. Effect of DALIRESP on Rate of Moderate or Severe Exacerbations 1. Absolute reduction measured as difference between placebo and roflumilast treated patients.
2. RR is Rate Ratio.
3. Percent reduction is defined as 100 (1-RR).
 
Study Exacerbations Per Patient-Year 
 DALIRESP Placebo Absolute Reduction1
 RR2 95% CI Percent Reduction3.
Trial 5 1.1 1.3 0.2 0.85 0.74, 0.98 15
Trial 6 1.2 1.5 0.3 0.82 0.71, 0.94 18
1. Absolute reduction measured as difference between placebo and roflumilast treated patients.
2. RR is Rate Ratio.
3. Percent reduction is defined as 100 (1-RR).
 
Study Exacerbations Per Patient-Year 
 DALIRESP Placebo Absolute Reduction1
 RR2 95% CI Percent Reduction3.
Trial 5 1.1 1.3 0.2 0.85 0.74, 0.98 15
Trial 6 1.2 1.5 0.3 0.82 0.71, 0.94 18

For patients in Trials 5 and 6 who received concomitant long-acting beta agonists or short-acting anti-muscarinics, reduction of moderate or severe exacerbations with DALIRESP was similar to that observed for the overall populations of the two trials.

Effect on Lung Function

While DALIRESP is not a bronchodilator, all 1-year trials (Trials 3, 4, 5, and 6) eva luated the effect of DALIRESP on lung function as determined by the difference in FEV1 between DALIRESP and placebo-treated patients (pre-bronchodilator FEV1 measured prior to study drug administration in three of the trials and post-bronchodilator FEV1 measured 30 minutes after administration of 4 puffs of albuterol/salbutamol in one trial) as a co-primary endpoint. In each of these trials DALIRESP 500 mcg once daily demonstrated a statistically significant improvement in FEV1 which averaged approximately 50 mL across the four trials. Table 3 shows FEV1 results from Trials 5 and 6 which had demonstrated a significant reduction in COPD exacerbations.

Table 3. Effect of DALIRESP on FEV1 1 Effect measured as difference between DALIRESP and placebo treated patients.
 
Study Change in FEV1from Baseline, mL
Trial 5
 DALIRESP Placebo Effect1 95% CI
46 8 39 18, 60
Trial 6
 33 -25 58 41, 75

Lung function was also eva luated in two 6-month trials (Trials 7 and 8) to assess the effect of DALIRESP when administered as add-on therapy to treatment with a long-acting beta agonist or a long-acting anti-muscarinic. These trials were conducted in a different population of COPD patients [moderate to severe COPD (FEV1 40 to 70% of predicted) without a requirement for chronic bronchitis or frequent history of exacerbations] from that for which efficacy in reduction of exacerbations has been demonstrated and provide safety support to the DALIRESP COPD program.

No trials have been conducted to assess the effects of DALIRESP on COPD exacerbations when added to a fixed-dose combination product containing a long-acting beta agonist and inhaled corticosteroid.

16 HOW SUPPLIED/STORAGE AND HANDLING
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