Table 1.
Summary of the clinical findings with roflumilast in COPD
| Study | Trial design | Primary outcome measurements | Findings | Reference |
|---|---|---|---|---|
| RECORD (1411 subjects) | Post-bronchodilator FEV1 (30–80%predicted value)
Roflumilast (250 μg, 500 μg) versus placebo 24 weeks |
Post-bronchodilator FEV1 St Georges respiratory Questionnaire scores (SGRQ) scores |
Post-bronchodilator FEV1 significantly improved compared with placebo
(250 μg: 74 ml [SD 18] and 500 μg 97 ml [SD18]) SGRQ improved though no difference between groups (Roflumilast 250 μg; −3.4 units; 500 μg; −3.5 units; placebo −1.8 units) |
Rabe et al 2005 |
| RATIO/M2-112 (1513 subjects) | Severe and very severe COPD
Roflumilast (500 μg), 52 weeks |
Post-bronchodilator FEV1 Frequency of moderate and severe exacerbations |
Significant improvement in FEV1 7% reduction in total exacerbations (P > 0.05) 18% Reduction in moderate exacerbations (P < 0.0.0147) |
Altana 2005 |
| Bronchodilator activity (15 subjects) | Mild to moderate asthmatics
Roflumilast (500 μg; 1000 μg versus placebo) 3 period (one day each) placebo controlled cross over study (7–14 day washout period) |
FEV1 measured for up to 6 h post treatment | Neither dose of roflumilast significantly altered FEV1 vs placebo
No evidence of direct bronchodilator activity |
Engelstatter et al 2005 |
| Sputum Analysis (38 subjects) | Post-bronchodilator FEV1 61% predicted
4 week crossover study 500 μg roflumilast placebo |
Sputum sample cell counts IL-8 and Neutrophil Elastase levels | Reduction in number of: neutrophils (35%) eosinophils (50%)
Reduction in the levels of IL8 (25.9%) neutrophil elastase (30.6%) |
Grootendorst et al 2005 |
| Withdrawal Study (581 subjects) | FEV1 35%–75% predicted
Roflumilast (500 μg) versus placebo for 12 weeks |
Post-bronchodilator FEV1 | In patients withdrawing from roflumilast FEV1 slowly declined over weeks but remained above placebo levels | Boszormenyi-Nagy et al 2005 |
| Safety (397 subjects) | Post-bronchodilator FEV1 (35%–75% predicted)
Roflumilast (500 μg), 52 weeks |
Adverse events | 49% during double blind period (same frequency all treatment groups) 41% during open label study.
Most mild to moderate and transient in nature >90% unrelated to study drug 10 patients (2.5%) experienced 13 adverse events which were definitely related to study drug. 3 lead to study discontinuation |
Bateman et al 2004 |
Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in one second; IL, interleukin; SD, standard deviation.