Trial record 1 of 1 for:
EFC13889
Evaluation of Alirocumab Versus Ezetimibe on Top of Statin in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY EAST)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02715726 |
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Recruitment Status :
Completed
First Posted : March 22, 2016
Results First Posted : September 30, 2019
Last Update Posted : September 30, 2019
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Sponsor:
Sanofi
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
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Brief Summary:
Primary Objective:
To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy in comparison to ezetimibe 10 mg daily after 24 weeks of treatment in Asia in participants with hypercholesterolemia at high cardiovascular (CV) risk.
Secondary Objectives:
- To evaluate the effect of alirocumab 75 mg in comparison with ezetimibe 10 mg on LDL-C after 12 weeks of treatment.
- To evaluate the effect of alirocumab on other lipid parameters: e.g., apolipoprotein B (Apo B), non-high density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), lipoprotein a (Lp[a]), HDL-C, triglycerides (TG), apolipoprotein A-1 (Apo A-1).
- To evaluate the safety and tolerability of alirocumab.
- To evaluate the development of anti-alirocumab antibodies.
- To evaluate the pharmacokinetics (PK) of alirocumab.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hypercholesterolemia | Drug: Alirocumab Drug: Placebo for alirocumab Drug: ezetimibe Drug: placebo for ezetimibe Drug: atorvastatin Drug: rosuvastatin Drug: simvastatin | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 615 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Statin Therapy |
| Actual Study Start Date : | July 27, 2016 |
| Actual Primary Completion Date : | August 6, 2018 |
| Actual Study Completion Date : | August 6, 2018 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Ezetimibe 10 mg
Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab every 2 weeks (Q2W) for 22 weeks added to lipid modifying therapy (LMT).
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Drug: Placebo for alirocumab
Pharmaceutical form:solution Route of administration: subcutaneous Drug: ezetimibe Pharmaceutical form:capsule Route of administration: oral Drug: atorvastatin Pharmaceutical form:tablet Route of administration: oral Drug: rosuvastatin Pharmaceutical form:tablet Route of administration: oral Drug: simvastatin Pharmaceutical form:tablet Route of administration: oral |
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Experimental: Alirocumab 75 mg Q2W/up to 150 mg Q2W
Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was >=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter [mmol/L]) at Week 8.
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Drug: Alirocumab
Pharmaceutical form:solution Route of administration: subcutaneous
Other Name: SAR236553 (REGN727) Drug: placebo for ezetimibe Pharmaceutical form:capsule Route of administration: oral Drug: atorvastatin Pharmaceutical form:tablet Route of administration: oral Drug: rosuvastatin Pharmaceutical form:tablet Route of administration: oral Drug: simvastatin Pharmaceutical form:tablet Route of administration: oral |
Primary Outcome Measures :
- Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted least square (LS) means and standard errors at Week 24 were obtained from mixed models analysis 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).
Secondary Outcome Measures :
- Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all 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, whichever came first) (on-treatment analysis).
- Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: On-Treatment Analysis [ Time Frame: From Baseline to Week 12 ]Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all 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, whichever came first) (on-treatment analysis).
- Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Apolipoprotein B at Week 24: On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all 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, whichever came first) (on-treatment analysis).
- 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 ]Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all 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, whichever came first) (on-treatment analysis).
- Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 up to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Total Cholesterol at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: ITT Analysis [ Time Frame: Up to Week 24 ]Adjusted percentages at Week 24 were obtained from multiple imputation approach 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.
- Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: On-Treatment Analysis [ Time Frame: Up to Week 24 ]Adjusted percentages at Week 24 were obtained from multiple imputation approach including all 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, whichever came first) (on-treatment analysis).
- Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 24: ITT Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling 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.
- Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 24: ITT Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted means and standard errors at Week 24 were obtained by using 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.
- Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24: ITT Analysis [ Time Frame: From Baseline to Week 24 ]Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]Adjusted means and standard errors at Week 12 were obtained 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.
- Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Fasting Triglycerides at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]Adjusted means and standard errors at Week 12 were obtained by using multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
- Percent Change From Baseline in Apolipoprotein A-1 at Week 12 : ITT Analysis [ Time Frame: From Baseline to Week 12 ]Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion criteria:
Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who are not adequately controlled with a maximally tolerated daily dose of statin at a stable dose for at least 4 weeks prior to the screening visit (Week -3).
Exclusion criteria:
- Participants without established CHD or CHD risk equivalents.
- LDL-C <70 mg/dL (<1.81 mmol/L) at the screening visit (Week -3) in participants with history of documented CV disease.
- LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (Week -3) in participants without history of documented CV disease.
- Change in statin dose or dose regimen from screening to randomization.
- Currently taking a statin other than atorvastatin, rosuvastatin, or simvastatin.
- Atorvastatin, rosuvastatin, or simvastatin was not taken daily or not taken at a registered dose.
- Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg.
- Use of cholesterol absorption inhibitor (ie, ezetimibe), omega-3 fatty acid (at doses ≥1000 mg daily), nicotinic acid, fibrates, bile acid-binding sequestrant, or red yeast rice products in the past 4 weeks prior to screening visit (Week -3).
- Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L) at the screening period.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02715726
Locations
Show 62 study locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
Study Documents (Full-Text)
Documents provided by Sanofi:
Documents provided by Sanofi:
Statistical Analysis Plan [PDF] October 17, 2017
Study Protocol [PDF] December 17, 2015
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT02715726 |
| Other Study ID Numbers: |
EFC13889 U1111-1150-8859 ( Other Identifier: UTN ) |
| First Posted: | March 22, 2016 Key Record Dates |
| Results First Posted: | September 30, 2019 |
| Last Update Posted: | September 30, 2019 |
| Last Verified: | September 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Additional relevant MeSH terms:
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Hypercholesterolemia Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Atorvastatin Rosuvastatin Calcium Simvastatin Ezetimibe Antibodies, Monoclonal |
Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors Immunologic Factors Physiological Effects of Drugs |