Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale

Lipids in Health and Disease

Research

Kimimasa Tobita¹  Akira Kondo¹  Arihiro Kiyosue²  Masataka Sata³  Mariko Harada-Shiba⁴  Yasushi Ishigaki⁵  Marie T. Baccara-Dinet⁶  Asuka Ozaki⁷  Yumiko Kawabata⁷  Tamio Teramoto⁸ 

[1] Asia Pacific Development, R&D, Sanofi, Tokyo, Japan;Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan;Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan;Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan;Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University, Iwate, Japan;PCSK9 Development and Launch Unit, Sanofi, Montpellier, France;Sanofi Japan, Tokyo, Japan;Teikyo Academic Research Center, Teikyo University, 2-11-1, Kaga, Itabashi-ku, 173-8605, Tokyo, Japan;

关键词: Alirocumab;    Hypercholesterolemia;    Statin;    Statin intolerance;    Cardiovascular risk;    PCSK9 inhibitor;    Lipids;   

DOI  :  10.1186/s12944-017-0513-7

 received in 2017-02-23, accepted in 2017-06-05,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundStatins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C).MethodsThe randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated.DiscussionThe ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone).Trial registrationClinicalTrials.gov number: NCT02584504

【 授权许可】

CC BY   
© The Author(s). 2017