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

Hypercholesterolemia Clinical Trial

— ODYSSEY EAST  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02715726
• Other study ID #: EFC13889
• Secondary ID: U1111-1150-8859
• Status: Completed
• Phase: Phase 3
• Start date: July 27, 2016
• Est. completion date: August 6, 2018

Study information

• Verified date: September 2019
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 615
• Est. completion date: August 6, 2018
• Est. primary completion date: August 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Alirocumab
Pharmaceutical form:solution Route of administration: subcutaneous
• Placebo for alirocumab
Pharmaceutical form:solution Route of administration: subcutaneous
• ezetimibe
Pharmaceutical form:capsule Route of administration: oral
• placebo for ezetimibe
Pharmaceutical form:capsule Route of administration: oral
• atorvastatin
Pharmaceutical form:tablet Route of administration: oral
• rosuvastatin
Pharmaceutical form:tablet Route of administration: oral
• simvastatin
Pharmaceutical form:tablet Route of administration: oral

Locations

Country	Name	City	State
China	Investigational Site Number 1560012	Beijing
China	Investigational Site Number 1560018	Beijing
China	Investigational Site Number 1560027	Beijing
China	Investigational Site Number 1560039	Beijing
China	Investigational Site Number 1560043	Beijing
China	Investigational Site Number 1560006	Changchun
China	Investigational Site Number 1560020	Changchun
China	Investigational Site Number 1560023	Changsha
China	Investigational Site Number 1560030	Fuzhou
China	Investigational Site Number 1560005	Guangzhou
China	Investigational Site Number 1560025	Guangzhou
China	Investigational Site Number 1560040	Guangzhou
China	Investigational Site Number 1560008	Hangzhou
China	Investigational Site Number 1560037	Hangzhou
China	Investigational Site Number 1560048	Hangzhou
China	Investigational Site Number 1560014	Hohhot
China	Investigational Site Number 1560016	Jinan
China	Investigational Site Number 1560044	Lanzhou
China	Investigational Site Number 1560028	Nanchang
China	Investigational Site Number 1560017	Nanjing
China	Investigational Site Number 1560031	Nanjing
China	Investigational Site Number 1560045	Nanjing
China	Investigational Site Number 1560035	Nanning
China	Investigational Site Number 1560029	Shanghai
China	Investigational Site Number 1560041	Shanghai
China	Investigational Site Number 1560053	Shanghai
China	Investigational Site Number 1560001	Shenyang
China	Investigational Site Number 1560009	Shenyang
China	Investigational Site Number 1560042	Shenyang
China	Investigational Site Number 1560036	Shenzhen
China	Investigational Site Number 1560056	Siping
China	Investigational Site Number 1560021	Taiyuan
China	Investigational Site Number 1560002	Tianjin
China	Investigational Site Number 1560022	Tianjin
China	Investigational Site Number 1560052	Tianjin
China	Investigational Site Number 1560055	Wenzhou
China	Investigational Site Number 1560003	Wuhan
China	Investigational Site Number 1560004	Xi'An
China	Investigational Site Number 1560019	Xuzhou
China	Investigational Site Number 1560054	Yinchuan
China	Investigational Site Number 1560057	Zhanjiang
India	Investigational Site Number 3560017	Belgaum
India	Investigational Site Number 3560001	Gurgaon
India	Investigational Site Number 3560003	Hubli
India	Investigational Site Number 3560010	Kolkata
India	Investigational Site Number 3560019	Kolkata
India	Investigational Site Number 3560020	Mangalore
India	Investigational Site Number 3560006	Mumbai
India	Investigational Site Number 3560004	Nagpur
India	Investigational Site Number 3560007	Nagpur
India	Investigational Site Number 3560008	Nagpur
India	Investigational Site Number 3560016	Nagpur
India	Investigational Site Number 3560014	New Delhi
India	Investigational Site Number 3560005	Pune
India	Investigational Site Number 3560011	Pune
India	Investigational Site Number 3560013	Surat
India	Investigational Site Number 3560015	Vijayawada
India	Investigational Site Number 3560012	Vijaywada
Thailand	Investigational Site Number 7640004	Bangkok
Thailand	Investigational Site Number 7640003	Bangkok-Noi
Thailand	Investigational Site Number 7640001	Muang
Thailand	Investigational Site Number 7640002	Pratumwan

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

China,  India,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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