PMID- 25499937
OWN - NLM
STAT- MEDLINE
DCOM- 20150930
LR  - 20200927
IS  - 1933-2874 (Print)
IS  - 1876-4789 (Linking)
VI  - 8
IP  - 6
DP  - 2014 Nov-Dec
TI  - Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in 
      statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a 
      randomized phase 3 trial.
PG  - 554-561
LID - S1933-2874(14)00331-6 [pii]
LID - 10.1016/j.jacl.2014.09.007 [doi]
AB  - 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      for 4 weeks, and were withdrawn if they developed muscle-related AEs after the 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.
CI  - Copyright (c) 2014 National Lipid Association. Published by Elsevier Inc. All 
      rights reserved.
FAU - Moriarty, Patrick M
AU  - Moriarty PM
AD  - Division of Clinical Pharmacology, Department of Internal Medicine, University of 
      Kansas Medical Center, Kansas City, Kansas, USA. Electronic address: 
      PMORIART@kumc.edu.
FAU - Jacobson, Terry A
AU  - Jacobson TA
AD  - Emory University, Atlanta, Georgia, USA.
FAU - Bruckert, Eric
AU  - Bruckert E
AD  - Hopital de la Pitie-Salpetriere, Paris, France.
FAU - Thompson, Paul D
AU  - Thompson PD
AD  - Hartford Hospital, Hartford, Connecticut, USA.
FAU - Guyton, John R
AU  - Guyton JR
AD  - Duke University Medical Center, Durham, North Carolina, USA.
FAU - Baccara-Dinet, Marie T
AU  - Baccara-Dinet MT
AD  - Sanofi, Montpellier, France.
FAU - Gipe, Daniel
AU  - Gipe D
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140919
PL  - United States
TA  - J Clin Lipidol
JT  - Journal of clinical lipidology
JID - 101300157
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Azetidines)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Pyrroles)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
RN  - EC 3.4.21.- (Proprotein Convertases)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EOR26LQQ24 (Ezetimibe)
RN  - PP0SHH6V16 (alirocumab)
SB  - IM
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Atorvastatin
MH  - Azetidines/administration & dosage/adverse effects
MH  - Canada
MH  - Cardiovascular Diseases/diagnosis/*drug therapy
MH  - Cholesterol, LDL/blood
MH  - Drug Dosage Calculations
MH  - Europe
MH  - Ezetimibe
MH  - Heptanoic Acids/administration & dosage/adverse effects
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Myalgia/etiology/prevention & control
MH  - Proprotein Convertase 9
MH  - Proprotein Convertases/*immunology
MH  - Pyrroles/administration & dosage/adverse effects
MH  - Risk
MH  - Serine Endopeptidases/*immunology
MH  - United States
OTO - NOTNLM
OT  - Alirocumab
OT  - Ezetimibe
OT  - Hypercholesterolemia
OT  - Muscle symptoms
OT  - PCSK9
OT  - Phase 3 clinical trial
OT  - Statin intolerance
OT  - Statin myopathy
EDAT- 2014/12/17 06:00
MHDA- 2015/10/01 06:00
CRDT- 2014/12/16 06:00
PHST- 2014/06/20 00:00 [received]
PHST- 2014/09/10 00:00 [revised]
PHST- 2014/09/15 00:00 [accepted]
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/10/01 06:00 [medline]
AID - S1933-2874(14)00331-6 [pii]
AID - 10.1016/j.jacl.2014.09.007 [doi]
PST - ppublish
SO  - J Clin Lipidol. 2014 Nov-Dec;8(6):554-561. doi: 10.1016/j.jacl.2014.09.007. Epub 
      2014 Sep 19.