HypercholesterolemiaPhase 3NCT01730053
Study of Alirocumab (REGN727/SAR236553) added-on to Rosuvastatin Versus Other Lipid Modifying Treatments (LMT) (ODYSSEY OPTIONS II)
A Phase 3 study testing Alirocumab, Rosuvastatin and Ezetimibe in people with Hypercholesterolemia, run by Regeneron Pharmaceuticals at 93 sites in 9 countries.
Trial summary
To evaluate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab (REGN727/SAR236553) as an add-on therapy to other LMT in patients with hypercholesterolemia at high cardiovascular (CV) risk. 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, Rosuvastatin and Ezetimibe
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 305 participants
- Where
- 93 sitesin 9 countries
- Study dates
- 30 Nov 2012to 31 May 2014
- 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
- 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
- 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.
Who cannot join
- LDL-C less than 70 mg/dL at the screening visit in patients with history of documented cardiovascular disease (CVD)
- LDL-C less than 100 mg/dL at the screening visit in patients without history of documented coronary heart disease (CHD) or non-CHD CVD, but with other risk factors
- Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping)
- Recent (within 3 months prior to the screening visit) myocardial infarction (MI), unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
- Newly diagnosed (within 3 months prior to randomization visit) or poorly controlled diabetes
- Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
- (The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial).
Trial locations and contacts
93 sites in 9 countries.
93 sites in 9 countries
United States54 sites
Study site
Anaheim, California
Study site
Atlantis, Florida
Study site
Auburn, Maine
Study site
Bethesda, Maryland
Study site
Beverly Hills, California
Study site
Boise, Idaho
Study site
Bountiful, Utah
Study site
Bradenton, Florida
Study site
Butte, Montana
Study site
Chandler, Arizona
Study site
Cincinnati, Ohio
Study site
Clearwater, Florida
Study site
Dallas, Texas
Study site
Edina, Minnesota
Study site
Evansville, Indiana
Study site
Fair Oaks, California
Study site
Fort Lauderdale, Florida
Study site
Fort Worth, Texas
Study site
Greer, South Carolina
Study site
Houston, Texas
Study site
Indianapolis, Indiana
Study site
Jacksonville, Florida
Study site
Kingsport, Tennessee
Study site
Lakeland, Florida
Study site
Lexington, Kentucky
Study site
Louisville, Kentucky
Study site
Marion, Ohio
(2 Locations)
Miami, Florida
Study site
Milford, Connecticut
Study site
Morton, Illinois
Study site
Newport Beach, California
Study site
Newton, Kansas
Study site
Northridge, California
Study site
Olive Branch, Mississippi
Study site
Overland Park, Kansas
Study site
Oviedo, Florida
Study site
Pinellas Park, Florida
Study site
Port Gibson, Mississippi
Study site
Port Orange, Florida
Study site
Portland, Oregon
Study site
Rochester, Minnesota
Study site
Sacramento, California
Study site
Salt Lake City, Utah
Study site
Sarasota, Florida
Study site
St Louis, Missouri
Study site
Summerville, South Carolina
Study site
Tampa, Florida
Study site
Tucson, Arizona
Study site
Walnut Creek, California
Study site
Warwick, Rhode Island
Study site
West Palm Beach, Florida
Study site
Wichita, Kansas
Study site
Williamsville, New York
Study site
Winter Park, Florida
Canada8 sites
Study site
Brampton, Ontario
Study site
Burlington, Ontario
Study site
Chicoutimi, Quebec
Study site
Etobicoke, Ontario
Study site
London, Ontario
Study site
Newmarket, Ontario
Study site
Thornhill, Ontario
Study site
Toronto, Ontario
Australia5 sites
Study site
Herston
Study site
New Lambton Heights
Study site
Perth
Study site
Sherwood
Study site
Woolloongabba
Germany5 sites
Study site
Bad Oeynhausen
Study site
Berlin
Study site
Cologne
Study site
Regensburg
Study site
Ulm
Italy5 sites
Study site
Chieti
Study site
Genova
Study site
Naples
Study site
Palermo
(2 Locations)
Roma
Mexico5 sites
Study site
Baja California
Study site
Distrito Federal
(3 Locations)
Guadalajara
Study site
Monterrey
Study site
Zapopan Jalisco
United Kingdom5 sites
Study site
Chester
Study site
Peterborough
Study site
Salford
Study site
Stevenage
Study site
West Bromwich, West Midlands
Spain4 sites
(2 Locations)
Barcelona
Study site
Madrid
Study site
Santiago
Study site
Seville
About this study
Official title: A Randomized, Double-Blind Study of the Efficacy and Safety of REGN727 Added-on to Rosuvastatin Versus Ezetimibe Added-on to Rosuvastatin Versus Rosuvastatin Dose Increase in Patients Who Are Not Controlled on Rosuvastatin
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.
- Conditions
- Hypercholesterolemia
- Being tested
- Alirocumab, Rosuvastatin, Ezetimibe, Placebo
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlirocumabDrug
Also called REGN727/SAR236553
Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
RosuvastatinDrug
Also called Crestor
Rosuvastatin over-encapsulated tablets orally.
EzetimibeDrug
Also called Ezetrol
Ezetimibe over-encapsulated tablets orally.
PlaceboDrug
Placebo for alirocumab and ezetimibe.
| Study group | Role | What they receive |
|---|---|---|
| Rosuvastatin 20 mg | Active comparator | 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. Receives: Drug: Rosuvastatin; Drug: Placebo |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Active comparator | 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. Receives: Drug: Rosuvastatin; Drug: Ezetimibe; Drug: Placebo |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Experimental | 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. Receives: Drug: Alirocumab; Drug: Rosuvastatin; Drug: Placebo |
| Rosuvastatin 40 mg | Active comparator | 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. Receives: Drug: Rosuvastatin; Drug: Placebo |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Active comparator | 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. Receives: Drug: Rosuvastatin; Drug: Ezetimibe; Drug: Placebo |
| Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg | Experimental | 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. Receives: Drug: Alirocumab; Drug: Rosuvastatin; Drug: Placebo |
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 at Week 24 - Intent-to-Treat (ITT) Analysis
Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Measured: From Baseline to Week 24
Secondary outcomes (23)
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Calculated LDL-C values were obtained from Friedewald formula. 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 (ie. up to 21 days after last injection or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first) (on-treatment analysis).
Measured: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Calculated LDL-C values were obtained from Friedewald formula. 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 (ITT analysis).
Measured: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 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 or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first) (on-treatment analysis).
Measured: From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein (Apo) B 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.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 - 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 (ie. up to 21 days after last injection or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first).
Measured: From Baseline to Week 24
Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) 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.
Measured: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 - 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 or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first).
Measured: From Baseline to Week 24
Percent Change From Baseline in Total Cholesterol (Total-C) 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.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo B 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.
Measured: From Baseline to Week 12
Percent Change From Baseline in Non-HDL-C 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.
Measured: From Baseline to Week 12
Percent Change From Baseline in Total-C 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.
Measured: From Baseline to Week 12
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis
Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a 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 analysis).
Measured: Up to Week 24
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis
Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a 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 or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first (on-treatment analysis).
Measured: Up to Week 24
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a 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 analysis).
Measured: Up to Week 24
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a 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 or 3 days after the last capsule [whatever rosuvastatin or ezetimibe], whichever came first (on-treatment analysis).
Measured: Up to Week 24
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in HDL-C 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.
Measured: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo A-1 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.
Measured: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Measured: From Baseline to Week 12
Percent Change From Baseline in HDL-C 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.
Measured: From Baseline to Week 12
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Measured: From Baseline to Week 12
Percent Change From Baseline in Apo A-1 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.
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 Nov 2012 (estimated)
- Study start30 Nov 2012
- Primary completion30 Apr 2014
- Study completion31 May 2014
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 (5)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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 305 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
- NCT01730053
- Sponsor's protocol ID
- R727-CL-1118
- Status last verified
- Mar 2020
- First submitted
- 9 Nov 2012
- Last updated
- 7 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 34298554Leiter 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.
PubMed 30183102Ray 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.
PubMed 27777279Farnier 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.
PubMed 26638010Robinson 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.
PubMed 25269777
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind Study of the Efficacy and Safety of REGN727 Added-on to Rosuvastatin Versus Ezetimibe Added-on to Rosuvastatin Versus Rosuvastatin Dose Increase in Patients Who Are Not Controlled on Rosuvastatin
- ClinicalTrials.gov ID
- NCT01730053
- Acronym / sponsor ID
- R727-CL-1118
- Conditions
- Hypercholesterolemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 305 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Study start
- 30 Nov 2012 (actual)
- Primary completion
- 30 Apr 2014 (actual)
- Study completion
- 31 May 2014 (actual)
- First posted
- 21 Nov 2012 (estimated)
- Results
- Posted 28 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Rosuvastatin 20 mg | Active comparator | Drug: Rosuvastatin, Drug: PlaceboParticipants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received rosuvastatin 20 mg over-encapsulated tablet orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablet orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks. |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | Active comparator | Drug: Rosuvastatin, Drug: Ezetimibe, Drug: PlaceboParticipants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | Experimental | Drug: Alirocumab, Drug: Rosuvastatin, Drug: PlaceboParticipants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. |
| Rosuvastatin 40 mg | Active comparator | Drug: Rosuvastatin, Drug: PlaceboParticipants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received rosuvastatin 40 mg over-encapsulated tablet orally QD, placebo for alirocumab Q2W SC injection, and placebo for ezetimibe QD over-encapsulated tablet orally added to stable LMT for 24 weeks. |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | Active comparator | Drug: Rosuvastatin, Drug: Ezetimibe, Drug: PlaceboParticipants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for alirocumab Q2W SC injection added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg | Experimental | Drug: Alirocumab, Drug: Rosuvastatin, Drug: PlaceboParticipants, 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
- 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.
Key exclusion criteria (7 listed)
- LDL-C less than 70 mg/dL at the screening visit in patients with history of documented cardiovascular disease (CVD)
- LDL-C less than 100 mg/dL at the screening visit in patients without history of documented coronary heart disease (CHD) or non-CHD CVD, but with other risk factors
- Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping)
- Recent (within 3 months prior to the screening visit) myocardial infarction (MI), unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
- Newly diagnosed (within 3 months prior to randomization visit) or poorly controlled diabetes
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 |
|---|---|---|
| AlirocumabAlso: REGN727/SAR236553Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm. | Drug | Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg |
| RosuvastatinAlso: CrestorRosuvastatin over-encapsulated tablets orally. | Drug | Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg, Ezetimibe 10 mg + Rosuvastatin 10 mg, Ezetimibe 10 mg + Rosuvastatin 20 mg, Rosuvastatin 20 mg, Rosuvastatin 40 mg |
| EzetimibeAlso: EzetrolEzetimibe over-encapsulated tablets orally. | Drug | Ezetimibe 10 mg + Rosuvastatin 10 mg, Ezetimibe 10 mg + Rosuvastatin 20 mg |
| PlaceboPlacebo for alirocumab and ezetimibe. | Drug | Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg, Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg, Ezetimibe 10 mg + Rosuvastatin 10 mg, Ezetimibe 10 mg + Rosuvastatin 20 mg, Rosuvastatin 20 mg, Rosuvastatin 40 mg |
Primary outcome
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
Time frame: From Baseline to Week 24
Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
23 secondary outcomes
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 - 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 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) 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 High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis
Time frame: Up to Week 24
Percentage of Participants 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 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) at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Time frame: From Baseline to Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34298554Mahmood 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.
- Derived from this study: PubMed 30183102Leiter 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.
- Derived from this study: PubMed 27777279Ray 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.
- Derived from this study: PubMed 26638010Farnier 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.
- Derived from this study: PubMed 25269777Robinson 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.
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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
93 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alirocumab, Rosuvastatin and Ezetimibe in people with Hypercholesterolemia, run by Regeneron Pharmaceuticals at 93 sites in 9 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 3 inclusion and 7 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 7 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 93 sites in United States, Canada, Australia, Germany, Italy and 4 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. 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 28 Oct 2015). 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 at Week 24 - Intent-to-Treat (ITT) Analysis (time frame: From Baseline to Week 24). 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 NCT01730053, which also lists 5 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 7 Apr 2020.