The Efficacy and Safety of Cilomilast in COPD

摘要

The aim of this review is to present the clinical data on the efficacy and safetyof cilomilast in patients with chronic obstructive pulmonary disease (COPD). Over 6000 COPD patients received cilomilast during an extensive clinical development programme performed by GlaxoSmithKline (GSK).Five phase III randomized, double-blind, placebo-controlled, parallel-group pivotal studies were conducted in poorly reversible patients (<15% or <200 mL improvement over baseline in forced expiratory volume in 1 second (FEV_1) after salbutamol). Patients were randomized to receive oral cilomilast 15 mg (n = 2088) or placebo (n = 1408) twice daily for 24 weeks. The co-primary efficacy variables were changes from baseline in trough (predose) FEV_1 and in total score of the St George's Respiratory Questionnaire (SGRQ).Additional studies were performed to investigate the anti-inflammatory actions of cilomilast by measuring inflammatory cells and mediators in biopsies and induced sputum; to assess the long-term effects of cilomilast; to assess the cardiac safety of cilomilast; and to assess the efficacy of cilomilast on hyperinflation. Results from one of the phase III and from one supportive study have been previously published.In the phase III pivotal studies, when averaged over 24 weeks, the mean change from baseline in FEV_1 in the cilomilast group showed improvement compared with placebo in all studies (range 24-44 mL treatment difference). When averaged over 24 weeks, there was a similar improvement in the mean total SGRQ score in both treatment groups with a decrease ranging from -1.8 to -4.2 units in the cilomilast group and 0.4 to -4.9 units in the placebo group.