Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study

Background Chronic obstructive pulmonary disease (COPD) is a common, progre ssive respiratory disease that causes great morbidity and mortality despite treatment. There is evidence for airway inflammation in COPD. Cilomilast i s an orally active, potent, selective phosphodiesterase type 4 inhibitor, w hich in vitro can affect cells thought to be of clinical importance in COPD . Our aim was to assess the safety, efficacy, and dose response of cilomila st in the treatment of patients with this disease. Methods We did a 6-week, randomised, dose-ranging study in 424 patients wit h COPD (forced expiratory volume in 1 s [FEV1] 46.8% of predicted, FEV1/for ced vital capacity [FVC] 54.6%, and postsalbutamol reversibility 5.4%). We randomly assigned individuals at 60 European centres to receive cilomilast 5 (n=109), 10 (n=102), or 15 (n=107) mg twice daily, or placebo (n=106). Th e main outcome measure was trough FEV1 before and after use of a bronchodil ator. Analyses were by intention to treat. Findings Cilomilast 15 mg twice daily significantly improved FEV1 compared with placebo (mean 130 mL vs -30 mL [95% CI 90-240] at week 6, p<0.0001). F VC and peak expiratory flow were also improved (p=0.001 and p<0.0001, respe ctively). Quality of life measures did not differ significantly between the groups. There were no significant differences in serious adverse events be tween the groups. Interpretation Cilomilast 15 mg twice daily might be an effective maintenan ce treatment for COPD. Further clinical studies are underway.