期刊
JOURNAL OF CLINICAL LIPIDOLOGY
卷 8, 期 6, 页码 554-561出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacl.2014.09.007
关键词
Alirocumab; Ezetimibe; Hypercholesterolemia; PCSK9; Phase 3 clinical trial; Statin intolerance; Muscle symptoms; Statin myopathy
资金
- Regeneron Pharmaceuticals, Inc. [CL1119, RGN1032]
- Amgen [AMG145 20110118]
- Kowa
- Lilly
- Novartis
- Sanofi
- Genzyme
- Pfizer
- Catabasis
- Esperion
- B. Braun
- Kaneka
- Danone
- NHLBI [R01HL098085-01, RO1HL081893]
- NIAMS [RO 1 NS40606]
- NCCAM [RC1AT005836-01]
- Genomas
- Roche
- Sanolfi
- Amarin
- Sanofi [EFC13786, EFC12492, EFC12732, LTS13463]
- Abbott
- Genzyme/Sanofi
- GlaxoSmithKline
- Amarin Pharma
- Inc/Sanofi
- Novella
- Merck
BACKGROUND: Statin intolerance has been a major limitation in the use of statins, especially at higher doses. New effective treatments are needed for lowering low-density lipoprotein cholesterol (LDL-C) in patients who cannot tolerate daily statin doses. OBJECTIVE: ODYSSEY ALTERNATIVE (NCT01709513) evaluates efficacy and safety of alirocumab, a fully human proprotein convertase subtilisin/kexin type 9 monoclonal antibody, in patients with well-documented statin intolerance and moderate to very high cardiovascular risk. METHODS: This is a phase 3, multicenter, randomized, double-blind, double-dummy study in statin-intolerant patients. Intolerance was defined as inability to take at least 2 different statins because of muscle-related adverse events (AEs), 1 at the lowest approved starting dose. Patients first received single-blind subcutaneous and oral placebo for 4 weeks, and were withdrawn if they developed muscle-related AEs after the placebo treatment. Continuing patients were randomized (2:2:1 ratio) to alirocumab 75 mg self-administered via single 1 mL prefilled pen. every 2 weeks or ezetimibe 10 mg/day or atorvastatin 20 mg/day (statin rechallenge), for 24 weeks. Alirocumab dose was increased to 150 mg every 2 weeks (also 1 mL) at week 12 depending on week 8 LDL-C level. The primary endpoint is percent change in LDL-C from baseline to week 24 by intent-to-treat analysis. Muscle-related AEs were assessed by spontaneous patient reports and clinic queries. RESULTS: A total of 314 patients have been randomized. CONCLUSIONS: This is the first and only study of a new class of LDL-C lowering agents in patients selected with a rigorously documented intolerance to statins, using a placebo run-in and statin control arm. (C) 2014 National Lipid Association. All rights reserved.
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