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.
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.
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DOI：
10.1186/s12944-017-0513-7
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发表时间：
2017-06-17
影响因子：
4.5
通讯作者：
Sata M
中科院分区：
文献类型：
--
作者：
Teramoto T;Kondo A;Kiyosue A;Harada-Shiba M;Ishigaki Y;Tobita K;Kawabata Y;Ozaki A;Baccara-Dinet MT;Sata M
他汀类药物通常耐受性良好，严重的副作用也很少见，但一些患者会出现不良事件，并减少他汀类药物剂量或完全停止治疗。Alibaba是一种针对前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK 9）的高度特异性全人单克隆抗体，可显著持续降低低密度脂蛋白胆固醇（LDL-C）。随机化、双盲、安慰剂对照、平行组、III期ODYSSEY NIPPON研究将在163例接受最低规格剂量阿托伐他汀（5 mg/天）或接受非他汀类降脂治疗（LLT）（非诺贝特、苯扎贝特、依折麦布或单独饮食治疗）的高胆固醇血症日本患者中探索alirocumab 150 mg每4周一次（Q4 W）。高胆固醇血症定义为杂合子家族性高胆固醇血症或非家族性高胆固醇血症患者（有记录的冠心病病史）的LDL-C ≥ 100 mg/dL（2.6 mmol/L），或分类为一级预防类别III的非家族性高胆固醇血症患者（即高风险患者）的LDL-C ≥120 mg/dL（3.1 mmol/L）。在12周双盲治疗期间，患者将随机（1：1：1）接受alirocumab皮下（SC）150 mg Q4 W与alirocumab安慰剂Q4 W交替治疗，或alirocumab 150 mg SC每2周一次（Q2 W）或SC安慰剂Q2 W。主要疗效终点是从基线至第12周LDL-C计算值的百分比变化。还将研究alirocumab的长期安全性和耐受性。ODYSSEY NIPPON研究将深入了解alirocumab 150 mg Q4 W或150 mg Q2 W在接受最低剂量阿托伐他汀或接受非他汀类LLT（包括单独饮食治疗）的日本高胆固醇血症患者中的疗效和安全性。 ClinicalTrials.gov编号：NCT 02584504
Statins 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). The 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. The 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). ClinicalTrials.gov number: NCT02584504