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, progressive respiratory disease that causes great morbidity and mortality despite treatment. There is evidence for airway inflammation in COPD. Cilomilast is an orally active, potent, selective phosphodiesterase type 4 inhibitor, which 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 cilomilast in the treatment of patients with this disease. Methods We did a 6-week, randomised, dose-ranging study in 424 patients with COPD (forced expiratory volume in 1 s [FEV1] 46.8% of predicted, FEV1/forced 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). The main outcome measure was trough FEV1 before and after use of a bronchodilator. 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). FVC and peak expiratory flow were also improved (p=0.001 and p<0.0001, respectively). Quality of life measures did not differ significantly between the groups. There were no significant differences in serious adverse events between the groups. Interpretation Cilomilast 15 mg twice daily might be an effective maintenance treatment for COPD. Further clinical studies are underway.