Evaluation of Alirocumab Versus Ezetimibe on Top of Statin in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY EAST)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: ezetimibe; Drug: atorvastatin; Drug: rosuvastatin; Drug: simvastatin; Drug: Placebo for alirocumab; Drug: Alirocumab; Drug: placebo for ezetimibe

Detailed Description

The maximum study duration was 35 weeks per participant, which included a screening period of up to 3 weeks, a 24-week randomized treatment period, and an 8-week post-treatment follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 615
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100029
    • Investigational Site Number 1560027
  • Beijing, China, 100034
    • Investigational Site Number 1560043
  • Beijing, China, 100053
    • Investigational Site Number 1560039
  • Beijing, China, 100730
    • Investigational Site Number 1560012
  • Beijing, China, 100730
    • Investigational Site Number 1560018
  • Changchun, China, 130021
    • Investigational Site Number 1560006
  • Changchun, China, 130021
    • Investigational Site Number 1560020
  • Changsha, China, 410011
    • Investigational Site Number 1560023
  • Fuzhou, China, 354200
    • Investigational Site Number 1560030
  • Guangzhou, China, 510080
    • Investigational Site Number 1560005
  • Guangzhou, China, 510080
    • Investigational Site Number 1560040
  • Guangzhou, China, 510120
    • Investigational Site Number 1560025
  • Hangzhou, China, 310014
    • Investigational Site Number 1560048
  • Hangzhou, China, 310015
    • Investigational Site Number 1560037
  • Hangzhou, China, 310016
    • Investigational Site Number 1560008
  • Hohhot, China, 010017
    • Investigational Site Number 1560014
  • Jinan, China, 250013
    • Investigational Site Number 1560016
  • Lanzhou, China, 730000
    • Investigational Site Number 1560044
  • Nanchang, China, 330006
    • Investigational Site Number 1560028
  • Nanjing, China, 210006
    • Investigational Site Number 1560045
  • Nanjing, China, 210008
    • Investigational Site Number 1560017
  • Nanjing, China, 210011
    • Investigational Site Number 1560031
  • Nanning, China, 530031
    • Investigational Site Number 1560035
  • Shanghai, China, 200025
    • Investigational Site Number 1560029
  • Shanghai, China, 200040
    • Investigational Site Number 1560041
  • Shanghai, China, 201199
    • Investigational Site Number 1560053
  • Shenyang, China, 110004
    • Investigational Site Number 1560009
  • Shenyang, China, 110016
    • Investigational Site Number 1560001
  • Shenyang, China, 110016
    • Investigational Site Number 1560042
  • Shenzhen, China, 518036
    • Investigational Site Number 1560036
  • Siping, China, 136000
    • Investigational Site Number 1560056
  • Taiyuan, China, 030001
    • Investigational Site Number 1560021
  • Tianjin, China, 300052
    • Investigational Site Number 1560002
  • Tianjin, China, 300121
    • Investigational Site Number 1560022
  • Tianjin, China, 300140
    • Investigational Site Number 1560052
  • Wenzhou, China, 325000
    • Investigational Site Number 1560055
  • Wuhan, China, 430022
    • Investigational Site Number 1560003
  • Xi'An, China, 710061
    • Investigational Site Number 1560004
  • Xuzhou, China, 221002
    • Investigational Site Number 1560019
  • Yinchuan, China, 750004
    • Investigational Site Number 1560054
  • Zhanjiang, China, 524001
    • Investigational Site Number 1560057
• India
  • Belgaum, India, 590010
    • Investigational Site Number 3560017
  • Gurgaon, India, 122001
    • Investigational Site Number 3560001
  • Hubli, India, 580021
    • Investigational Site Number 3560003
  • Kolkata, India, 700020
    • Investigational Site Number 3560010
  • Kolkata, India, 700073
    • Investigational Site Number 3560019
  • Mangalore, India, 575002
    • Investigational Site Number 3560020
  • Mumbai, India
    • Investigational Site Number 3560006
  • Nagpur, India, 440003
    • Investigational Site Number 3560007
  • Nagpur, India, 440010
    • Investigational Site Number 3560004
  • Nagpur, India, 440012
    • Investigational Site Number 3560008
  • Nagpur, India, 440012
    • Investigational Site Number 3560016
  • New Delhi, India, 110002
    • Investigational Site Number 3560014
  • Pune, India, 411001
    • Investigational Site Number 3560005
  • Pune, India, 411001
    • Investigational Site Number 3560011
  • Surat, India, 395002
    • Investigational Site Number 3560013
  • Vijayawada, India, 520008
    • Investigational Site Number 3560015
  • Vijaywada, India, 520002
    • Investigational Site Number 3560012
• Thailand
  • Bangkok, Thailand, 10400
    • Investigational Site Number 7640004
  • Bangkok-Noi, Thailand, 10700
    • Investigational site number 7640003
  • Muang, Thailand, 50200
    • Investigational site number 7640001
  • Pratumwan, Thailand, 10400
    • Investigational site number 7640002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	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; Drug: Placebo for alirocumab; Pharmaceutical form:solution Route of administration: subcutaneous
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.	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; Drug: Alirocumab; Pharmaceutical form:solution Route of administration: subcutaneous; Other Names: SAR236553 (REGN727); Drug: placebo for ezetimibe; Pharmaceutical form:capsule Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis	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).	From Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis	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).	From Baseline to Week 24
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: ITT Analysis	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.	From Baseline to Week 12
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: On-Treatment Analysis	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).	From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Analysis	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.	From Baseline to Week 24
Percent Change From Baseline in Apolipoprotein B at Week 24: On-Treatment Analysis	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).	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 were obtained from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis	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).	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 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.	From Baseline to Week 24
Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Analysis	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.	From Baseline to Week 12
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Analysis	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.	From Baseline to Week 12
Percent Change From Baseline in Total Cholesterol at Week 12: ITT Analysis	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.	From Baseline to Week 12
Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: ITT Analysis	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.	Up to Week 24
Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: On-Treatment Analysis	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).	Up to Week 24
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 24: ITT Analysis	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.	From Baseline to Week 24
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 24: ITT Analysis	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.	From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Analysis	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.	From Baseline to Week 24
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24: ITT Analysis	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.	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 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.	From Baseline to Week 12
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12: ITT Analysis	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.	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 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.	From Baseline to Week 12
Percent Change From Baseline in Apolipoprotein A-1 at Week 12 : ITT Analysis	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.	From Baseline to Week 12

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Han Y, Chen J, Chopra VK, Zhang S, Su G, Ma C, Huang Z, Ma Y, Yao Z, Yuan Z, Zhao Q, Kuanprasert S, Baccara-Dinet MT, Manvelian G, Li J, Chen R. ODYSSEY EAST: Alirocumab efficacy and safety vs ezetimibe in high cardiovascular risk patients with hypercholesterolemia and on maximally tolerated statin in China, India, and Thailand. J Clin Lipidol. 2020 Jan-Feb;14(1):98-108.e8. doi: 10.1016/j.jacl.2019.10.015. Epub 2019 Nov 18.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2016
• Primary Completion (Actual): August 6, 2018
• Study Completion (Actual): August 6, 2018

Study Registration Dates

• First Submitted: March 16, 2016
• First Submitted That Met QC Criteria: March 16, 2016
• First Posted (Estimate): March 22, 2016

Study Record Updates

• Last Update Posted (Actual): September 30, 2019
• Last Update Submitted That Met QC Criteria: September 9, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Immunologic Factors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium; Antibodies, Monoclonal; Simvastatin; Ezetimibe
• Other Study ID Numbers: EFC13889; U1111-1150-8859 (Other Identifier: UTN)

Drug and device information, study documents

• 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