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

Lancet. 2001 Jul 28;358(9278):265-70. doi: 10.1016/S0140-6736(01)05481-2.

Abstract

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 [FEV(1)] 46.8% of predicted, FEV(1)/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 FEV(1) before and after use of a bronchodilator. Analyses were by intention to treat.

Findings: Cilomilast 15 mg twice daily significantly improved FEV(1) 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Bronchodilator Agents / therapeutic use*
  • Carboxylic Acids
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cyclohexanecarboxylic Acids
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Europe
  • Female
  • Humans
  • Lung Diseases, Obstructive / drug therapy*
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Nitriles
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Quality of Life
  • Respiratory Function Tests
  • Surveys and Questionnaires

Substances

  • Bronchodilator Agents
  • Carboxylic Acids
  • Cyclohexanecarboxylic Acids
  • Nitriles
  • Phosphodiesterase Inhibitors
  • Cilomilast
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4