Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab (REGN727/ SAR236553) in Patients With Primary Hypercholesterolemia (ODYSSEY CHOICE 1)

NCT ID: NCT01926782

Last Updated: 2017-03-21

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

803 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2015-04-30

Brief Summary

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To determine the efficacy, long-term safety, and tolerability of alirocumab 300 mg every 4 weeks (Q4W), in comparison with placebo, as well as its potential as a starting regimen. The dose regimen of 75 mg every 2 weeks (Q2W), as used in other studies, was added as a calibrator.

Detailed Description

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Conditions

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Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study was conducted in 2 separate populations concurrently: subjects receiving concomitant statin therapy and subjects not receiving concomitant statin therapy. Subjects receiving concomitant statin were to receive stable daily doses of rosuvastatin, atorvastatin, or simvastatin for at least 4 weeks. Background treatment with other lipid-modifying therapy (LMT) was allowed for all patients, provided they had been on a stable dose for at least 4 weeks (6 weeks for fenofibrate) prior to study entry.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo Q2W

Two subcutaneous (SC) injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks.

Group Type PLACEBO_COMPARATOR

Placebo (for alirocumab)

Intervention Type DRUG

Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Statin

Intervention Type DRUG

Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy

Alirocumab 75 mg/ Up 150 mg Q2W

One SC injection of each Alirocumab 75 mg and placebo Q2W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.

Group Type EXPERIMENTAL

Placebo (for alirocumab)

Intervention Type DRUG

Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Alirocumab

Intervention Type DRUG

Solution for injection, subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Statin

Intervention Type DRUG

Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy

Alirocumab 300 mg/ Up 150 mg Q4W

Two SC injections of Alirocumab 150 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.

Group Type EXPERIMENTAL

Placebo (for alirocumab)

Intervention Type DRUG

Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Alirocumab

Intervention Type DRUG

Solution for injection, subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Statin

Intervention Type DRUG

Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy

Interventions

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Placebo (for alirocumab)

Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Intervention Type DRUG

Alirocumab

Solution for injection, subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Intervention Type DRUG

Statin

Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy

Intervention Type DRUG

Other Intervention Names

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SAR236553 REGN727 Praluent

Eligibility Criteria

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Inclusion Criteria

1. Men and women \> age 18 or legal age of majority with elevated LDL-C
2. Patients not having adequate control of their hypercholesterolemia based on their individual level of CVD risk
3. Willing and able to comply with clinic visits and study-related procedures
4. Provided signed informed consent

Exclusion Criteria

1. Recent (within 3 months prior to the screening visit) myocardial infarction, unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
2. Known history of positive test for human immunodeficiency virus (HIV)
3. Any clinically significant abnormality identified at the time of screening that in the judgment of the investigator or any sub-investigator would preclude safe completion of the study or constrain assessment of endpoints, such as major systemic diseases or participants with short life expectancy.
4. Participants considered by the investigator or any sub-investigator to be inappropriate for this study (e.g, geographic or social), actual or anticipated, that the investigator felt would restrict or limit the participant's participation for the duration of the study.
5. Certain laboratory findings obtained during the screening period
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

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Goodyear, Arizona, United States

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Carmichael, California, United States

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Fresno, California, United States

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West Hills, California, United States

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Wildomar, California, United States

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Colorado Springs, Colorado, United States

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Golden, Colorado, United States

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Boynton Beach, Florida, United States

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Jacksonville, Florida, United States

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Safety Harbor, Florida, United States

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Atlanta, Georgia, 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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Gurnee, Illinois, United States

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Evansville, Indiana, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Kansas City, Kansas, United States

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Louisville, Kentucky, United States

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Monroe, Louisiana, United States

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Auburn, Maine, United States

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Methuen, Massachusetts, United States

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Minneapolis, Minnesota, United States

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St Louis, Missouri, United States

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Rochester, New York, United States

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Farmville, North Carolina, United States

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Greensboro, North Carolina, United States

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Greenville, North Carolina, United States

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Raleigh, North Carolina, United States

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Wilson, North Carolina, United States

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Cincinnati, Ohio, United States

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Marion, Ohio, United States

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Tulsa, Oklahoma, United States

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Philadelphia, Pennsylvania, United States

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Wyomissing, Pennsylvania, United States

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Knoxville, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Orem, Utah, United States

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Salt Lake City, Utah, United States

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South Jordan, Utah, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Kenosha, Wisconsin, United States

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Varna, Varna, Bulgaria

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Sofia, , Bulgaria

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Victoria, British Columbia, Canada

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Oshawa, Ontario, Canada

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Toronto, Ontario, Canada

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Woodstock, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Trois-Rivières, Quebec, Canada

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Budapest, Becsi Ut, Hungary

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Debrecen, HBM, Hungary

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Nyíregyháza, Sz-sz-b_m, Hungary

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Ajka, Veszprém, Hungary

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Nagykanizsa, Zala County, Hungary

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Zalaegerszeg, Zala County, Hungary

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Tel Litwinsky, IL, Israel

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Safed, ISR, Israel

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Ofakim, South, Israel

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Holon, , Israel

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Tel Litwinsky, , Israel

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Skedsmokorset, Akershus, Norway

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Oslo, , Norway

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Svidník, Presov, Slovakia

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Bratislava, SK, Slovakia

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Bratislava, SR, Slovakia

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Lučenec, , Slovakia

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Považská Bystrica, , Slovakia

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Worton Grange, Reading, Berkshire, United Kingdom

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Edgbaston, Birmingham, United Kingdom

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Llanishen, Cardiff, United Kingdom

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Choley, Lancashire, United Kingdom

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Waterloo, Liverpool, United Kingdom

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Lloyd Street North, Manchester, United Kingdom

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Glasgow, Scotland, United Kingdom

Site Status

Countries

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United States Bulgaria Canada Hungary Israel Norway Slovakia United Kingdom

References

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Roth EM, Kastelein JJP, Cannon CP, Farnier M, McKenney JM, DiCioccio AT, Brunet A, Manvelian G, Sasiela WJ, Baccara-Dinet MT, Zhao J, Robinson JG. Pharmacodynamic relationship between PCSK9, alirocumab, and LDL-C lowering in the ODYSSEY CHOICE I trial. J Clin Lipidol. 2020 Sep-Oct;14(5):707-719. doi: 10.1016/j.jacl.2020.07.009. Epub 2020 Jul 25.

Reference Type DERIVED
PMID: 32928709 (View on PubMed)

Muller-Wieland D, Rader DJ, Moriarty PM, Bergeron J, Langslet G, Ray KK, Manvelian G, Thompson D, Bujas-Bobanovic M, Roth EM. Efficacy and Safety of Alirocumab 300 mg Every 4 Weeks in Individuals With Type 2 Diabetes on Maximally Tolerated Statin. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5253-5262. doi: 10.1210/jc.2018-02703.

Reference Type DERIVED
PMID: 31166599 (View on PubMed)

Roth EM, Moriarty PM, Bergeron J, Langslet G, Manvelian G, Zhao J, Baccara-Dinet MT, Rader DJ; ODYSSEY CHOICE I investigators. A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I. Atherosclerosis. 2016 Nov;254:254-262. doi: 10.1016/j.atherosclerosis.2016.08.043. Epub 2016 Aug 31.

Reference Type DERIVED
PMID: 27639753 (View on PubMed)

Other Identifiers

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R727-CL-1308

Identifier Type: -

Identifier Source: org_study_id

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