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Cilomilast for COPD^*

Results of a 6-Month, Placebo-Controlled Study of a Potent, Selective Inhibitor of Phosphodiesterase 4

Stephen I. Rennard, MD, FCCP; Neil Schachter, MD; Mary Strek, MD; Kathy Rickard, MD and Ohad Amit, PhD

^* From the University of Nebraska Medical Center (Dr. Rennard), Omaha, NE; Mount Sinai Medical Center (Dr. Schachter), New York, NY; the University of Chicago (Dr. Strek), Chicago, IL; and GlaxoSmithKline (Drs. Rickard and Amit), Research Triangle Park, NC. A list of participating investigators is located in the ^Appendix.

Correspondence to: Stephen I. Rennard, MD, FCCP; Larson Professor of Medicine, University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, NE 68198-5885; e-mail: srennard{at}unmc.edu

Abstract

Background: COPD is a relentless, progressive disease. This study evaluated the efficacy of cilomilast, a selective phosphodiesterase (PDE) 4 inhibitor, in the treatment of COPD.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study in subjects with COPD. After a 4-week, single-blind, placebo run-in period, eligible subjects were randomized in a 2:1 ratio to receive oral cilomilast, 15 mg bid, or placebo for 24 weeks. Subjects between 40 and 80 years of age who had received a diagnosis of COPD were eligible for the study. The primary efficacy variables were changes from baseline in trough (ie, predose) FEV₁ and in total score of the St. George’s Respiratory Questionnaire (SGRQ). A key secondary end point was the incidence rate of COPD exacerbations.

Results: The average change from baseline in FEV₁ over 24 weeks in the cilomilast group was an increase of 10 mL compared with a decrease of 30 mL in the placebo group (difference, 40 mL; p = 0.002). When averaged over 24 weeks, there was a clinically significant reduction in the mean total SGRQ score in subjects receiving cilomilast therapy, with a difference of 4.1 U compared with subjects who received placebo (p = 0.001). A greater percentage of subjects in the cilomilast group were exacerbation-free at 24 weeks (74%; p = 0.008) compared with placebo (62%). Adverse events were generally mild or moderate and were not unexpected for this class of medications. GI adverse events that interfered with daily activities (cilomilast, 17%; placebo, 8%) predominantly occurred within the first 3 weeks of initiating cilomilast therapy.

Conclusion: Cilomilast is an orally active, potent, and selective inhibitor of PDE-4. Cilomilast maintained pulmonary function and improved health status, and reduced the rate of COPD exacerbations during 24 weeks of treatment. This study supports the use of cilomilast, a novel, selective PDE-4 inhibitor, in subjects with COPD.

Key Words: cilomilast • COPD • phosphodiesterase-4 • phosphodiesterase-4 enzyme

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