A phase I/IIa trial of atorvastatin in Japanese patients with acute Kawasaki disease and coronary artery aneurysms

Abstract Background In the United States, a phase I/IIa dose‐escalation study of atorvastatin in Kawasaki disease (KD) patients with coronary artery aneurysms (CAAs) demonstrated the safety and pharmacokinetics (PK) of atorvastatin. However, the tolerability and PK of atorvastatin in Japanese KD patients with CAAs remain unknown. Methods This multicenter, single‐arm, open‐label, phase I/IIa study of atorvastatin in acute KD patients with CAAs in Japan recruited patients for a 3 + 3 dose‐escalation study of a 6‐week course of atorvastatin (0.125–0.5 mg/kg/day). The primary outcome was the safety of atorvastatin. The secondary outcomes were the PK of atorvastatin, biomarkers of inflammation, and echocardiographic assessment of CAAs. Results We enrolled nine KD patients in this study. No dose‐limiting toxicity was observed. Therefore, we determined the maximum tolerated dose was 0.5 mg/kg/day. Although there were no serious adverse drug reactions, two participants showed minor elevations in aspartate or alanine aminotransferase that recovered spontaneously without discontinuation of atorvastatin. The Z‐scores of each coronary artery decreased from baseline to the 6‐week visit except for one lesion. The serum concentration of atorvastatin was similar to those reported in PK studies of atorvastatin conducted in children with KD in the United States between the ages of 2 and 17 years. No significant differences in estimated PK parameters were observed in each dose group compared to previous studies. Conclusions We found that atorvastatin was safe and a dose up to 0.5 mg/kg/day for 6 weeks was well‐tolerated in Japanese children with acute KD and CAAs.