Patients with COPD are known to be at increased risk of cardiovascular (CV) disease. To evaluate the CV safety of cilomilast (CIL) in patients with COPD, an integration of the CV safety data across four pivotal studies was conducted.
Electrocardiogram (ECG), vital sign (VS) and adverse event (AE) data were integrated from four 24-week, randomized, double-blind, placebo-controlled, parallel-group studies in COPD patients evaluating CIL 15mg BID versus placebo. Routine ECGs and VSs were evaluated at baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24 and premature discontinuation. Additional ECGs were conducted 3 hours post study drug administration (Cmax ECGs) at baseline and week 24.
A total of 2883 COPD patients were evaluated (1091 placebo vs 1792 CIL). Demographic and pulmonary function characteristics were similar between treatment groups, with patient ages ranging between 39-84 years, mean smoking history of 53 vs. 51 pack years and mean FEV1 of 50% vs. 50% of predicted (placebo vs CIL, respectively). Forty eight percent of the placebo vs. 52% of CIL treated patients had underlying cardiac conditions. Mean changes from baseline to endpoint (EP) in SBP (-0.7 vs. -1.8 mmHg), DBP (-0.6 vs. -0.9 mmHg) and HR (0.7 vs. 0.9 bpm) were similar between placebo vs CIL treatment groups, respectively.Changes in routine ECGs from baseline to EP in ventricular rate, QRS axis, QTc, and the occurrence of treatment emergent ECG abnormalities were similar between treatment groups. Comparable findings were also observed when assessing Cmax ECGs. The incidence of CV AEs was similar between treatment groups.CONCLUSIONS: The CV safety profile of CIL is similar to that of placebo in patients with moderate to severe COPD, many of whom have concomitant cardiac conditions.CLINCIAL IMPLICATIONS: CV disease is common in COPD patients. These results suggest that cilomilast may be used safely in patients with COPD.
QTcB (Bazett’s correction) and QTcF (Fridericia’s correction) Change from Baseline at EPParameter for Routine ECGsPlacebo (n=1091)Cilomilast (n=1792)QTcB (Baseline, Change from Baseline at EP)424msec, 0.1msec425msec, -0.4msecQTcF (Baseline, Change from Baseline at EP)412msec, -1.2msec413msec, -1.9msec
G. Ferguson, GlaxoSmithKline, discussion of product research or unlabeled uses of product.