Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I)
A Randomized, Double-Blind Study of the Efficacy and Safety of Alirocumab Added on to Atorvastatin Versus Ezetimibe Added on to Atorvastatin Versus Atorvastatin Dose Increase Versus Switch to Rosuvastatin in Patients Who Are Not Controlled on Atorvastatin
1 other identifier
interventional
355
9 countries
97
Brief Summary
This is a randomized, double-blind, active-comparator, parallel-group study in patients at high cardiovascular risk with nonfamilial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH).
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 Oct 2012
97 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
Study Start
First participant enrolled
October 1, 2012
CompletedFirst Submitted
Initial submission to the registry
November 9, 2012
CompletedFirst Posted
Study publicly available on registry
November 21, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2014
CompletedResults Posted
Study results publicly available
August 31, 2015
CompletedAugust 31, 2015
July 1, 2015
1.5 years
November 9, 2012
July 29, 2015
July 29, 2015
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 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
From Baseline to Week 24
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 (7)
Atorvastatin 40 mg
ACTIVE COMPARATORParticipants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.
Ezetimibe 10 mg + Atorvastatin 20 mg
ACTIVE COMPARATORParticipants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg
EXPERIMENTALParticipants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets 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.
Atorvastatin 80 mg
ACTIVE COMPARATORParticipants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.
Rosuvastatin 40 mg
ACTIVE COMPARATORParticipants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received rosuvastatin 40 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.
Ezetimibe 10 mg + Atorvastatin 40 mg
ACTIVE COMPARATORParticipants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg
EXPERIMENTALParticipants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets 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.
Atorvastatin over-encapsulated tablets orally.
Ezetimibe over-encapsulated tablet orally.
Rosuvastatin over-encapsulated tablets orally.
Placebo for alirocumab and ezetimibe.
Eligibility Criteria
You may qualify if:
- Patients with screening (visit 1) LDL-C greater than or equal to 70 mg/dL with documented CVD, not adequately controlled with a daily dose of atorvastatin. OR
- Patients with screening (visit 1) LDL-C greater than or equal to 100 mg/dL at high risk for CVD who are not adequately controlled with a daily dose of atorvastatin.
You may not qualify if:
- LDL-C greater than 250 mg/dL
- LDL-C less than 70 mg/dL at the screening visit in patients with history of documented CVD
- LDL-C less than 100 mg/dL at the screening visit in patients without history of documented CHD or non-CHD CVD, but with other risk factors
- TG greater than 400 mg/dL
- Homozygous FH (clinically or previous genotyping)
- Currently taking a statin that is not atorvastatin
- Currently taking Ezetimibe (EZE)
- Not on a stable dose of allowable lipid modifying treatments (LMT)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Regeneron Pharmaceuticalslead
- Sanoficollaborator
Study Sites (97)
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Mobile, Alabama, United States
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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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Lakeland Village, 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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Boca Raton, Florida, United States
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Clearwater, Florida, United States
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Jacksonville, Florida, United States
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Miami (2 Locations), 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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Boise, Idaho, United States
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Meridian, Idaho, United States
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Chicago, Illinois, United States
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Morton, Illinois, 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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Las Vegas, Nevada, United States
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Williamsville, New York, United States
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Winston-Salem, North Carolina, United States
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Cleveland, Ohio, United States
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Oklahoma City, Oklahoma, 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 (2 Locations), 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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Marion, Utah, United States
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Salt Lake City, Utah, United States
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Renton, Washington, United States
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Herston QLD, 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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Etobicoke, Ontario, Canada
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London, Ontario, Canada
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Newmarke, 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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Vénissieux, France
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Bad Oeynhausen, Germany
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Berlin, Germany
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Cologne, Germany
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Munich, Germany
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Regensburg, Germany
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Ulm, Germany
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Chiete, Italy
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Genova, Italy
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Napoli, Italy
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Palermo, Italy
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Roma (2 Locations), Italy
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Distrito Federal, Mexico
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Guadalajara, Mexico
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Guadalajara, Jalisco, Mexico
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Monterrey Nuevo Leon, Mexico
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Tijuana Baja California, Mexico
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Zapopan Jalisco, Mexico
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Barcelona (3 Locations), Spain
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Madrid, Spain
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Sant Joan Despí, Spain
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Carmarthen, 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
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West Bromwich, West Midlands, 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: 27777279DERIVEDBays H, Gaudet D, Weiss R, Ruiz JL, Watts GF, Gouni-Berthold I, Robinson J, Zhao J, Hanotin C, Donahue S. Alirocumab as Add-On to Atorvastatin Versus Other Lipid Treatment Strategies: ODYSSEY OPTIONS I Randomized Trial. J Clin Endocrinol Metab. 2015 Aug;100(8):3140-8. doi: 10.1210/jc.2015-1520. Epub 2015 Jun 1.
PMID: 26030325DERIVEDRobinson 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, Inc
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
October 1, 2012
Primary Completion
April 1, 2014
Study Completion
May 1, 2014
Last Updated
August 31, 2015
Results First Posted
August 31, 2015
Record last verified: 2015-07