Study of Alirocumab (REGN727/SAR236553) added-on to Rosuvastatin Versus Other Lipid Modifying Treatments (LMT) (ODYSSEY OPTIONS II)
A Randomized, Double-Blind Study of the Efficacy and Safety of REGN727 Added-on to Rosuvastatin Versus Ezetimibe Added-on to Rosuvastatin Versus Rosuvastatin Dose Increase in Patients Who Are Not Controlled on Rosuvastatin
1 other identifier
interventional
305
9 countries
93
Brief Summary
To evaluate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab (REGN727/SAR236553) as an add-on therapy to other LMT in patients with hypercholesterolemia at high cardiovascular (CV) risk.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2012
93 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2012
CompletedFirst Posted
Study publicly available on registry
November 21, 2012
CompletedStudy Start
First participant enrolled
November 30, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
May 31, 2014
CompletedResults Posted
Study results publicly available
October 28, 2015
CompletedApril 7, 2020
March 1, 2020
1.4 years
November 9, 2012
July 29, 2015
March 26, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
From Baseline to Week 24
Secondary Outcomes (23)
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis
From Baseline to Week 24
- +18 more secondary outcomes
Study Arms (6)
Rosuvastatin 20 mg
ACTIVE COMPARATORParticipants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received rosuvastatin 20 mg over-encapsulated tablet orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablet orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.
Ezetimibe 10 mg + Rosuvastatin 10 mg
ACTIVE COMPARATORParticipants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg
EXPERIMENTALParticipants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Rosuvastatin 40 mg
ACTIVE COMPARATORParticipants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received rosuvastatin 40 mg over-encapsulated tablet orally QD, placebo for alirocumab Q2W SC injection, and placebo for ezetimibe QD over-encapsulated tablet orally added to stable LMT for 24 weeks.
Ezetimibe 10 mg + Rosuvastatin 20 mg
ACTIVE COMPARATORParticipants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for alirocumab Q2W SC injection added to stable LMT for 24 weeks.
Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg
EXPERIMENTALParticipants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg Q2W SC injection, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Interventions
Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
Rosuvastatin over-encapsulated tablets orally.
Ezetimibe over-encapsulated tablets orally.
Placebo for alirocumab and ezetimibe.
Eligibility Criteria
You may qualify if:
- Patients with LDL-C greater than or equal to 70 mg/dL at the screening visit and who are not adequately controlled with a stable daily dose of rosuvastatin, with or without other LMT.
- Patients with screening LDL-C greater than or equal to 100 mg/dL who are not adequately controlled with a stable daily dose of rosuvastatin before the screening visit, with or without other LMT.
You may not qualify if:
- LDL-C less than 70 mg/dL at the screening visit in patients with history of documented cardiovascular disease (CVD)
- LDL-C less than 100 mg/dL at the screening visit in patients without history of documented coronary heart disease (CHD) or non-CHD CVD, but with other risk factors
- Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping)
- Recent (within 3 months prior to the screening visit) myocardial infarction (MI), unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
- Newly diagnosed (within 3 months prior to randomization visit) or poorly controlled diabetes
- Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Regeneron Pharmaceuticalslead
- Sanoficollaborator
Study Sites (93)
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Chandler, Arizona, United States
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Tucson, Arizona, United States
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Anaheim, California, United States
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Beverly Hills, California, United States
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Fair Oaks, California, United States
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Newport Beach, California, United States
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Northridge, California, United States
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Sacramento, California, United States
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Walnut Creek, California, United States
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Milford, Connecticut, United States
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Atlantis, Florida, United States
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Bradenton, Florida, United States
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Clearwater, Florida, United States
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Fort Lauderdale, Florida, United States
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Jacksonville, Florida, United States
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Lakeland, Florida, United States
(2 Locations)
Miami, Florida, United States
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Oviedo, Florida, United States
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Pinellas Park, Florida, United States
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Port Orange, Florida, United States
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Sarasota, Florida, United States
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Tampa, Florida, United States
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West Palm Beach, Florida, United States
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Winter Park, Florida, United States
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Boise, Idaho, United States
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Morton, Illinois, United States
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Evansville, Indiana, United States
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Indianapolis, Indiana, United States
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Newton, Kansas, United States
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Overland Park, Kansas, United States
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Wichita, Kansas, United States
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Lexington, Kentucky, United States
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Louisville, Kentucky, United States
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Auburn, Maine, United States
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Bethesda, Maryland, United States
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Edina, Minnesota, United States
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Rochester, Minnesota, United States
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Olive Branch, Mississippi, United States
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Port Gibson, Mississippi, United States
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St Louis, Missouri, United States
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Butte, Montana, United States
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Williamsville, New York, United States
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Cincinnati, Ohio, United States
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Marion, Ohio, United States
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Portland, Oregon, United States
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Warwick, Rhode Island, United States
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Greer, South Carolina, United States
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Summerville, South Carolina, United States
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Kingsport, Tennessee, United States
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Dallas, Texas, United States
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Fort Worth, Texas, United States
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Houston, Texas, United States
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Bountiful, Utah, United States
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Salt Lake City, Utah, United States
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Herston, Australia
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New Lambton Heights, Australia
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Perth, Australia
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Sherwood, Australia
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Woolloongabba, Australia
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Brampton, Ontario, Canada
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Burlington, Ontario, Canada
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Etobicoke, Ontario, Canada
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London, Ontario, Canada
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Newmarket, Ontario, Canada
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Thornhill, Ontario, Canada
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Toronto, Ontario, Canada
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Chicoutimi, Quebec, Canada
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Dijon, France
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Lille, France
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Bad Oeynhausen, Germany
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Berlin, Germany
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Cologne, Germany
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Regensburg, Germany
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Ulm, Germany
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Chieti, Italy
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Genova, Italy
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Napoli, Italy
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Palermo, Italy
(2 Locations)
Roma, Italy
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Baja California, Mexico
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Distrito Federal, Mexico
(3 Locations)
Guadalajara, Mexico
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Monterrey, Mexico
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Zapopan Jalisco, Mexico
(2 Locations)
Barcelona, Spain
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Madrid, Spain
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Santiago, Spain
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Seville, Spain
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West Bromwich, West Midlands, United Kingdom
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Chester, United Kingdom
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Peterborough, United Kingdom
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Salford, United Kingdom
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Stevenage, United Kingdom
Related Publications (5)
Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.
PMID: 34298554DERIVEDLeiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
PMID: 30183102DERIVEDRay KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.116.024604. Epub 2016 Oct 24.
PMID: 27777279DERIVEDFarnier M, Jones P, Severance R, Averna M, Steinhagen-Thiessen E, Colhoun HM, Du Y, Hanotin C, Donahue S. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial. Atherosclerosis. 2016 Jan;244:138-46. doi: 10.1016/j.atherosclerosis.2015.11.010. Epub 2015 Nov 14.
PMID: 26638010DERIVEDRobinson JG, Colhoun HM, Bays HE, Jones PH, Du Y, Hanotin C, Donahue S. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014 Oct;37(10):597-604. doi: 10.1002/clc.22327. Epub 2014 Sep 30.
PMID: 25269777DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Management
- Organization
- Regeneron Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Clinical Trial Management
Regeneron Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2012
First Posted
November 21, 2012
Study Start
November 30, 2012
Primary Completion
April 30, 2014
Study Completion
May 31, 2014
Last Updated
April 7, 2020
Results First Posted
October 28, 2015
Record last verified: 2020-03