Clinical trial NCT02715726: Evaluation of Alirocumab Versus Ezetimibe on Top of Statin in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2016-03-22
Enrollment: 615
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: On-Treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apolipoprotein B at Week 24: On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: ITT Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: On-Treatment Analysis
timeFrame: Up to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 24: ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 24: ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24: ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Fasting Triglycerides at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apolipoprotein A-1 at Week 12 : ITT Analysis
timeFrame: From Baseline to Week 12
Other outcomes:
Locations:
city: Beijing
country: China
facility: Investigational Site Number 1560027
city: Beijing
country: China
facility: Investigational Site Number 1560043
city: Beijing
country: China
facility: Investigational Site Number 1560039
city: Beijing
country: China
facility: Investigational Site Number 1560012
city: Beijing
country: China
facility: Investigational Site Number 1560018
city: Changchun
country: China
facility: Investigational Site Number 1560006
city: Changchun
country: China
facility: Investigational Site Number 1560020
city: Changsha
country: China
facility: Investigational Site Number 1560023
city: Fuzhou
country: China
facility: Investigational Site Number 1560030
city: Guangzhou
country: China
facility: Investigational Site Number 1560005
city: Guangzhou
country: China
facility: Investigational Site Number 1560040
city: Guangzhou
country: China
facility: Investigational Site Number 1560025
city: Hangzhou
country: China
facility: Investigational Site Number 1560048
city: Hangzhou
country: China
facility: Investigational Site Number 1560037
city: Hangzhou
country: China
facility: Investigational Site Number 1560008
city: Hohhot
country: China
facility: Investigational Site Number 1560014
city: Jinan
country: China
facility: Investigational Site Number 1560016
city: Lanzhou
country: China
facility: Investigational Site Number 1560044
city: Nanchang
country: China
facility: Investigational Site Number 1560028
city: Nanjing
country: China
facility: Investigational Site Number 1560045
city: Nanjing
country: China
facility: Investigational Site Number 1560017
city: Nanjing
country: China
facility: Investigational Site Number 1560031
city: Nanning
country: China
facility: Investigational Site Number 1560035
city: Shanghai
country: China
facility: Investigational Site Number 1560029
city: Shanghai
country: China
facility: Investigational Site Number 1560041
city: Shanghai
country: China
facility: Investigational Site Number 1560053
city: Shenyang
country: China
facility: Investigational Site Number 1560009
city: Shenyang
country: China
facility: Investigational Site Number 1560001
city: Shenyang
country: China
facility: Investigational Site Number 1560042
city: Shenzhen
country: China
facility: Investigational Site Number 1560036
city: Siping
country: China
facility: Investigational Site Number 1560056
city: Taiyuan
country: China
facility: Investigational Site Number 1560021
city: Tianjin
country: China
facility: Investigational Site Number 1560002
city: Tianjin
country: China
facility: Investigational Site Number 1560022
city: Tianjin
country: China
facility: Investigational Site Number 1560052
city: Wenzhou
country: China
facility: Investigational Site Number 1560055
city: Wuhan
country: China
facility: Investigational Site Number 1560003
city: Xi'An
country: China
facility: Investigational Site Number 1560004
city: Xuzhou
country: China
facility: Investigational Site Number 1560019
city: Yinchuan
country: China
facility: Investigational Site Number 1560054
city: Zhanjiang
country: China
facility: Investigational Site Number 1560057
city: Belgaum
country: India
facility: Investigational Site Number 3560017
city: Gurgaon
country: India
facility: Investigational Site Number 3560001
city: Hubli
country: India
facility: Investigational Site Number 3560003
city: Kolkata
country: India
facility: Investigational Site Number 3560010
city: Kolkata
country: India
facility: Investigational Site Number 3560019
city: Mangalore
country: India
facility: Investigational Site Number 3560020
city: Mumbai
country: India
facility: Investigational Site Number 3560006
city: Nagpur
country: India
facility: Investigational Site Number 3560007
city: Nagpur
country: India
facility: Investigational Site Number 3560004
city: Nagpur
country: India
facility: Investigational Site Number 3560008
city: Nagpur
country: India
facility: Investigational Site Number 3560016
city: New Delhi
country: India
facility: Investigational Site Number 3560014
city: Pune
country: India
facility: Investigational Site Number 3560005
city: Pune
country: India
facility: Investigational Site Number 3560011
city: Surat
country: India
facility: Investigational Site Number 3560013
city: Vijayawada
country: India
facility: Investigational Site Number 3560015
city: Vijaywada
country: India
facility: Investigational Site Number 3560012
city: Bangkok-Noi
country: Thailand
facility: Investigational Site Number 7640003
city: Bangkok
country: Thailand
facility: Investigational Site Number 7640004
city: Muang
country: Thailand
facility: Investigational Site Number 7640001
city: Pratumwan
country: Thailand
facility: Investigational Site Number 7640002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.