Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies)
American Journal of Cardiology
We assessed the safety and tolerability of ascending single doses of alirocumab in healthy Japanese subjects and evaluated the effect of alirocumab at 3 doses (50, 75, 150 mg) on lowdensity lipoprotein cholesterol (LDL-C) reduction in patients with primary hypercholesterolemia on atorvastatin. A randomized, single ascending-dose study of alirocumab (100, 150, 250, or 300 mg) or placebo (3:1 ratio), administered subcutaneously, was conducted in 32 healthy Japanese men. The phase 2, randomized,
... se 2, randomized, double-blind, placebo-controlled, parallel-group study was performed in patients with primary hypercholesterolemia (defined as calculated LDL-C ‡100 mg/dl [2.6 mmol/l]) who were on a stable dose of atorvastatin (5 to 20 mg). Patients were randomized to alirocumab (50, 75, or 150 mg) or placebo (in single 1.0-ml injection volumes) administered every 2 weeks (Q2W) for 12 weeks; the primary outcome was the mean percent change in calculated LDL-C from baseline to week 12. Single subcutaneous administration of alirocumab in healthy subjects was well tolerated over 15 weeks and resulted in highest mean percent reductions in LDL-C from baseline of approximately 40% to 60%. In the multiple-dose study, least-square mean (SE) changes in calculated LDL-C concentrations from baseline to week 12 were L54.8% (3.1%) for alirocumab 50 mg, L62.3% (3.1%) for alirocumab 75 mg, and L71.7% (3.1%) for alirocumab 150 mg, with a least-square mean (SE) difference versus placebo of L52.2% (4.3%), L59.6% (4.3%), and L69.1% (4.3%), respectively (all p <0.0001). In conclusion, alirocumab was well tolerated and significantly reduced LDL-C concentrations in Japanese patients with primary hypercholesterolemia on atorvastatin. Ó 2016 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). (Am J Cardiol 2016;118:56e63) The risk of coronary artery disease and all-cause mortality rises in association with increasing concentrations of low-density lipoprotein cholesterol (LDL-C) in both Japanese and Western populations. 1e6 The NIPPON DATA80 trial 7 and the Japan Lipid Intervention Trial (J-LIT) 3 emphasized the importance of risk factors, including dyslipidemia, hypertension, diabetes, smoking, and obesity, in relation to cardiovascular events in the Japanese population.