Study of Alirocumab (REGN727/SAR236553) added-on to Rosuvastatin Versus Other Lipid Modifying Treatments (LMT) (ODYSSEY OPTIONS II)

NCT ID: NCT01730053

Last Updated: 2020-04-07

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

305 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-30

Study Completion Date

2014-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Rosuvastatin 20 mg

Participants, 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.

Group Type ACTIVE_COMPARATOR

Rosuvastatin

Intervention Type DRUG

Rosuvastatin over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Ezetimibe 10 mg + Rosuvastatin 10 mg

Participants, 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.

Group Type ACTIVE_COMPARATOR

Rosuvastatin

Intervention Type DRUG

Rosuvastatin over-encapsulated tablets orally.

Ezetimibe

Intervention Type DRUG

Ezetimibe over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg

Participants, 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.

Group Type EXPERIMENTAL

Alirocumab

Intervention Type DRUG

Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

Rosuvastatin

Intervention Type DRUG

Rosuvastatin over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Rosuvastatin 40 mg

Participants, 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.

Group Type ACTIVE_COMPARATOR

Rosuvastatin

Intervention Type DRUG

Rosuvastatin over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Ezetimibe 10 mg + Rosuvastatin 20 mg

Participants, 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.

Group Type ACTIVE_COMPARATOR

Rosuvastatin

Intervention Type DRUG

Rosuvastatin over-encapsulated tablets orally.

Ezetimibe

Intervention Type DRUG

Ezetimibe over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg

Participants, 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.

Group Type EXPERIMENTAL

Alirocumab

Intervention Type DRUG

Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

Rosuvastatin

Intervention Type DRUG

Rosuvastatin over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Interventions

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Alirocumab

Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

Intervention Type DRUG

Rosuvastatin

Rosuvastatin over-encapsulated tablets orally.

Intervention Type DRUG

Ezetimibe

Ezetimibe over-encapsulated tablets orally.

Intervention Type DRUG

Placebo

Placebo for alirocumab and ezetimibe.

Intervention Type DRUG

Other Intervention Names

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REGN727/SAR236553 Crestor Ezetrol

Eligibility Criteria

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Inclusion Criteria

1. 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.

OR
2. 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.

Exclusion Criteria

1. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented cardiovascular disease (CVD)
2. 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
3. Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping)
4. 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
5. Newly diagnosed (within 3 months prior to randomization visit) or poorly controlled diabetes
6. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Chandler, Arizona, United States

Site Status

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

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(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

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(2 Locations)

Roma, , Italy

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Baja California, , Mexico

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Distrito Federal, , Mexico

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(3 Locations)

Guadalajara, , Mexico

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Monterrey, , Mexico

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Zapopan Jalisco, , Mexico

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(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

Site Status

Countries

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United States Australia Canada France Germany Italy Mexico Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 34298554 (View on PubMed)

Leiter 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.

Reference Type DERIVED
PMID: 30183102 (View on PubMed)

Ray 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.

Reference Type DERIVED
PMID: 27777279 (View on PubMed)

Farnier 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.

Reference Type DERIVED
PMID: 26638010 (View on PubMed)

Robinson 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.

Reference Type DERIVED
PMID: 25269777 (View on PubMed)

Other Identifiers

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R727-CL-1118

Identifier Type: -

Identifier Source: org_study_id

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