HypercholesterolemiaPhase 3NCT01926782
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)
A Phase 3 study testing Alirocumab and Statin in people with Hypercholesterolemia, run by Regeneron Pharmaceuticals at 83 sites in 8 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- Alirocumab and Statin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 803 participants
- Where
- 83 sitesin 8 countries
- Study dates
- Sep 2013to Apr 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women > age 18 or legal age of majority with elevated LDL-C
- Patients not having adequate control of their hypercholesterolemia based on their individual level of CVD risk
- Willing and able to comply with clinic visits and study-related procedures
- Provided signed informed consent
Who cannot join
- 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
- Known history of positive test for human immunodeficiency virus (HIV)
- 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.
- 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.
- Certain laboratory findings obtained during the screening period
- The information listed above is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial and not all inclusion/ exclusion criteria are listed.
Trial locations and contacts
83 sites in 8 countries.
83 sites in 8 countries
United States49 sites
Study site
Atlanta, Georgia
Study site
Auburn, Maine
Study site
Boise, Idaho
Study site
Boynton Beach, Florida
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Carmichael, California
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Chandler, Arizona
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Chicago, Illinois
Study site
Cincinnati, Ohio
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Colorado Springs, Colorado
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Dallas, Texas
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Evansville, Indiana
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Farmville, North Carolina
Study site
Fresno, California
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Golden, Colorado
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Goodyear, Arizona
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Greensboro, North Carolina
Study site
Greenville, North Carolina
Study site
Gurnee, Illinois
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Houston, Texas
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Indianapolis, Indiana
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Iowa City, Iowa
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Jacksonville, Florida
Study site
Kansas City, Kansas
Study site
Kenosha, Wisconsin
Study site
Knoxville, Tennessee
Study site
Louisville, Kentucky
Study site
Marion, Ohio
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Meridian, Idaho
Study site
Methuen, Massachusetts
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Minneapolis, Minnesota
Study site
Monroe, Louisiana
Study site
Norfolk, Virginia
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Orem, Utah
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Philadelphia, Pennsylvania
Study site
Raleigh, North Carolina
Study site
Richmond, Virginia
Study site
Rochester, New York
Study site
Safety Harbor, Florida
Study site
Salt Lake City, Utah
Study site
San Antonio, Texas
Study site
South Jordan, Utah
Study site
Spokane, Washington
Study site
St Louis, Missouri
Study site
Tacoma, Washington
Study site
Tulsa, Oklahoma
Study site
West Hills, California
Study site
Wildomar, California
Study site
Wilson, North Carolina
Study site
Wyomissing, Pennsylvania
Canada7 sites
Study site
Montreal, Quebec
Study site
Oshawa, Ontario
Study site
Québec, Quebec
Study site
Toronto, Ontario
Study site
Trois-Rivières, Quebec
Study site
Victoria, British Columbia
Study site
Woodstock, Ontario
United Kingdom7 sites
Study site
Choley, Lancashire
Study site
Edgbaston, Birmingham
Study site
Glasgow, Scotland
Study site
Llanishen, Cardiff
Study site
Lloyd Street North, Manchester
Study site
Waterloo, Liverpool
Study site
Worton Grange, Reading, Berkshire
Hungary6 sites
Study site
Ajka, Veszprém
Study site
Budapest, Becsi Ut
Study site
Debrecen, HBM
Study site
Nagykanizsa, Zala County
Study site
Nyíregyháza, Sz-sz-b_m
Study site
Zalaegerszeg, Zala County
Israel5 sites
Study site
Holon
Study site
Ofakim, South
Study site
Safed, ISR
Study site
Tel HaShomer, IL
Study site
Tel HaShomer
Slovakia5 sites
Study site
Bratislava, SK
Study site
Bratislava, SR
Study site
Lučenec
Study site
Považská Bystrica
Study site
Svidník, Presov
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab in Patients With Primary Hypercholesterolemia
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.
- Conditions
- Hypercholesterolemia
- Being tested
- Placebo (for alirocumab), Alirocumab, Statin
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo (for alirocumab)Drug
Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector.
AlirocumabDrug
Also called SAR236553, REGN727, Praluent
Solution for injection, subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.
StatinDrug
Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy
| Study group | Role | What they receive |
|---|---|---|
| Placebo Q2W | Placebo comparator | Two subcutaneous (SC) injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks. Receives: Drug: Placebo (for alirocumab); Drug: Statin |
| Alirocumab 75 mg/ Up 150 mg Q2W | Experimental | 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. Receives: Drug: Placebo (for alirocumab); Drug: Alirocumab; Drug: Statin |
| Alirocumab 300 mg/ Up 150 mg Q4W | Experimental | 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. Receives: Drug: Placebo (for alirocumab); Drug: Alirocumab; Drug: Statin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 24 and at averaged Week 21 to 24 from MMRM including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects without concomitant statin therapy): all randomized subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C in Participants Receiving Concomitant Statin Therapy - Intent-to-Treat (ITT Analysis)
Adjusted least squares (LS) means and standard errors at Week 24 and at averaged Week 21 to 24 were obtained from a mixed effect model with repeated measures (MMRM) model 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 this model (ITT analysis). ITT population (subjects with concomitant statin therapy): all randomized subjects who received concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Secondary outcomes (46)
Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis). Modified ITT (mITT) population (subjects with or without concomitant statin therapy): all randomized and treated subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis). Modified ITT (mITT) population (subjects with or without concomitant statin therapy): all randomized and treated subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - On-treatment Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - On-treatment Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). Subjects of the mITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). Subjects of the mITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline non-HDL-C value on-treatment (non-HDL-C mITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Total-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline Total-C value on- or off-treatment (Total-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Apo B ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Apo B at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Apo B ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Non-HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Non-HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Total-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Total-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Total-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Total-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C<70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C<100 mg/dL (Without Concomitant Statin Therapy) at Week 24 - ITT Analysis
Very high CV risk: history of documented coronary heart disease (CHD) or CHD risk equivalent. High CV risk: calculated 10-year fatal CVD risk score ≥5%, moderate chronic kidney disease, type 1/type 2 diabetes mellitus (DM) without target organ damage, or heFH not meeting definition of very high risk. Moderate CV risk: calculated 10-year fatal CVD risk score ≥1 \&<5%. CHD risk equivalent: peripheral arterial disease, ischemic stroke, transient ischemic attack, abdominal aortic aneurysm, carotid artery(CA)occlusion>50%, carotid endarterectomy/CA stent procedure, renal artery stenosis/stent procedure, type 1/type 2 DM with target organ damage. Adjusted percentages at Week 24 obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment included in imputation model. ITT population (subjects with or without concomitant statin therapy).
Measured: Up to Week 24
Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (With Concomitant Statin Therapy) at Week 24 - ITT Analysis
Very high CV risk: history of documented coronary heart disease (CHD) or CHD risk equivalent. High CV risk: calculated 10-year fatal CVD risk score ≥5%, moderate chronic kidney disease, type 1/type 2 diabetes mellitus (DM) without target organ damage, or heFH not meeting definition of very high risk. Moderate CV risk: calculated 10-year fatal CVD risk score ≥1 \&<5%. CHD risk equivalent: peripheral arterial disease, ischemic stroke, transient ischemic attack, abdominal aortic aneurysm, carotid artery(CA)occlusion>50%, carotid endarterectomy/CA stent procedure, renal artery stenosis/stent procedure, type 1/type 2 DM with target organ damage. Adjusted percentages at Week 24 obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment included in imputation model. ITT population (subjects with or without concomitant statin therapy).
Measured: Up to Week 24
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C<70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C<100 mg/dL(2.59 mmol/L) (Without Concomitant Statin Therapy) at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: Up to Week 24
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL(1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL(2.59 mmol/L) (With Concomitant Statin Therapy) at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: Up to Week 24
Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: Up to Week 24
Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: Up to Week 24
Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: Up to Week 24
Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). mITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: Up to Week 24
Percent Change From Baseline in Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment were included in the imputation model. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment were included in the imputation model. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (with or without concomitant statin therapy) with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm
Measured: From Baseline to Week 24
Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. HDL-C ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (subjects with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Subjects of the ITT population (subjects with or without concomitant statin therapy) with one baseline and at least one post-baseline Apo A1 value on- or off-treatment (Apo A1 ITT population). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Apo A1 ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Percent Change From Baseline in Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. Apo A1 ITT population (subjects with or without concomitant statin therapy). Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Measured: From Baseline to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2013 (estimated)
- Study startSep 2013
- Primary completionSep 2014
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 803 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01926782
- Sponsor's protocol ID
- R727-CL-1308
- Status last verified
- Jan 2017
- First submitted
- 19 Aug 2013
- Last updated
- 21 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 32928709Muller-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.
PubMed 31166599Roth 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.
PubMed 27639753
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab in Patients With Primary Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT01926782
- Acronym / sponsor ID
- R727-CL-1308
- Conditions
- Hypercholesterolemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 803 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Study start
- Sep 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 21 Aug 2013 (estimated)
- Results
- Posted 21 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Placebo Q2W | Placebo comparator | Drug: Placebo (for alirocumab), Drug: StatinTwo subcutaneous (SC) injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks. |
| Alirocumab 75 mg/ Up 150 mg Q2W | Experimental | Drug: Placebo (for alirocumab), Drug: Alirocumab, Drug: StatinOne 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. |
| Alirocumab 300 mg/ Up 150 mg Q4W | Experimental | Drug: Placebo (for alirocumab), Drug: Alirocumab, Drug: StatinTwo 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women > age 18 or legal age of majority with elevated LDL-C
- Patients not having adequate control of their hypercholesterolemia based on their individual level of CVD risk
- Willing and able to comply with clinic visits and study-related procedures
- Provided signed informed consent
Key exclusion criteria (6 listed)
- 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
- Known history of positive test for human immunodeficiency virus (HIV)
- 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.
- 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.
- Certain laboratory findings obtained during the screening period
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo (for alirocumab)Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector. | Drug | Alirocumab 300 mg/ Up 150 mg Q4W, Alirocumab 75 mg/ Up 150 mg Q2W, Placebo Q2W |
| AlirocumabAlso: SAR236553, REGN727, PraluentSolution for injection, subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector. | Drug | Alirocumab 300 mg/ Up 150 mg Q4W, Alirocumab 75 mg/ Up 150 mg Q2W |
| StatinAtorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy | Drug | Alirocumab 300 mg/ Up 150 mg Q4W, Alirocumab 75 mg/ Up 150 mg Q2W, Placebo Q2W |
Primary outcome
Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 24
Adjusted LS means and standard errors at Week 24 and at averaged Week 21 to 24 from MMRM including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects without concomitant statin therapy): all randomized subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Percent Change From Baseline in Calculated LDL-C in Participants Receiving Concomitant Statin Therapy - Intent-to-Treat (ITT Analysis)
Time frame: From Baseline to Week 24
Adjusted least squares (LS) means and standard errors at Week 24 and at averaged Week 21 to 24 were obtained from a mixed effect model with repeated measures (MMRM) model 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 this model (ITT analysis). ITT population (subjects with concomitant statin therapy): all randomized subjects who received concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
46 secondary outcomes
Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - On-treatment Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - On-treatment Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Total-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Apo B at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Total-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Total-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
Time frame: From Baseline to Week 12
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C<70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C<100 mg/dL (Without Concomitant Statin Therapy) at Week 24 - ITT Analysis
Time frame: Up to Week 24
Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (With Concomitant Statin Therapy) at Week 24 - ITT Analysis
Time frame: Up to Week 24
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C<70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C<100 mg/dL(2.59 mmol/L) (Without Concomitant Statin Therapy) at Week 24 - On-Treatment Analysis
Time frame: Up to Week 24
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL(1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL(2.59 mmol/L) (With Concomitant Statin Therapy) at Week 24 - On-Treatment Analysis
Time frame: Up to Week 24
Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Time frame: Up to Week 24
Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Time frame: Up to Week 24
Percentage of Participants (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Time frame: Up to Week 24
Percentage of Participants (With Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Time frame: Up to Week 24
Percent Change From Baseline in Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32928709Roth 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.
- Derived from this study: PubMed 31166599Muller-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.
- Derived from this study: PubMed 27639753Roth 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trial Management study director
Regeneron Pharmaceuticals
83 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alirocumab and Statin in people with Hypercholesterolemia, run by Regeneron Pharmaceuticals at 83 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 83 sites in United States, Canada, United Kingdom, Hungary, Israel and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis (time frame: From Baseline to Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01926782, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2017.