Table 2. Major clinical trials of roflumilast in COPD.
| Clinical trials and investigators | Year | Duration (weeks) | Primary objective | Treatment arms |
|---|---|---|---|---|
| RECORD (M2-127): Rabe et al. (51) | 2005 | 24 | Post-BD FEV1, SGRQ | RF 500 µg OD, RF 250 µg OD vs. placebo |
| RATIO (M2-112): Calverley et al. (53) | 2007 | 52 | Post-BD FEV1, AECOPD | RF 500 µg OD vs. placebo |
| OPUS (M2-111): Calverley et al. (53) | 2008 | 52 | Post-BD FEV1, AECOPD | RF 500 µg OD vs. placebo |
| AURA (M2-124), HERMES (M2-125): Calverley et al. (52) | 2009 | 52 | Pre-BD FEV1, AECOPD | RF 500 µg OD vs. placebo |
| EOS (M2-127): Fabbri et al. (60) | 2009 | 24 | Pre-BD FEV1 | RF 500 µg OD vs. placebo |
| Helios (M2-128): Fabbri et al. (60) | 2009 | 24 | Pre-BD FEV1 | RF 500 µg OD vs. placebo |
| ACROSS: Zheng et al. (61) | 2014 | 24 | Pre-BD and post-BD FEV1 | RF 500 µg OD vs. placebo (ICS-LABA allowed) |
| REACT: Calverley et al. (57), Martinez et al. (58) |
2012 2015 |
52 | Rate of moderate to severe AECOPD | RF 500 µg OD vs. placebo (COPD were pre-treated with ICS-LABA with or without LAMA for 12 months) |
| RE [2] SPOND: Martinez et al. (59) | 2016 | 52 | Rate of moderate to severe AECOPD | RF 500 µg OD vs. placebo (COPD were pre-treated with ICS-LABA with or without LAMA for 3 months) |
RF, roflumilast; OD, once-daily dose; FEV1, forced expiratory volume at 1 second; BD, bronchodilator; AECOPD, rate of COPD exacerbation; SGRQ, St. George’s Respiratory Questionnaire; ICS-LABA, combined inhaled corticosteroid and long-acting beta-agonist; LAMA, long acting antimuscarinic antagonist.