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

NCT02715726 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: EFC13889U1111-1150-8859
• Study Type: interventional
• Target: 615
• Locations: 3 countries
• Sites: 62

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.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (21)

• Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: ITT Analysis

  From Baseline to Week 12

• Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: On-Treatment Analysis

  From Baseline to Week 12

• Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Apolipoprotein B at Week 24: On-Treatment Analysis

  From Baseline to Week 24

Study Arms (2)

Ezetimibe 10 mg

ACTIVE COMPARATOR

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: Placebo for alirocumab; Drug: ezetimibe; Drug: atorvastatin; Drug: rosuvastatin; Drug: simvastatin

Alirocumab 75 mg Q2W/up to 150 mg Q2W

EXPERIMENTAL

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: Alirocumab; Drug: placebo for ezetimibe; Drug: atorvastatin; Drug: rosuvastatin; Drug: simvastatin

Interventions

Alirocumab DRUG

Pharmaceutical form:solution Route of administration: subcutaneous

Also known as: SAR236553 (REGN727)

Alirocumab 75 mg Q2W/up to 150 mg Q2W

Placebo for alirocumab DRUG

Pharmaceutical form:solution Route of administration: subcutaneous

Ezetimibe 10 mg

ezetimibe DRUG

Pharmaceutical form:capsule Route of administration: oral

Ezetimibe 10 mg

placebo for ezetimibe DRUG

Pharmaceutical form:capsule Route of administration: oral

Alirocumab 75 mg Q2W/up to 150 mg Q2W

atorvastatin DRUG

Pharmaceutical form:tablet Route of administration: oral

Alirocumab 75 mg Q2W/up to 150 mg Q2W; Ezetimibe 10 mg

rosuvastatin DRUG

Pharmaceutical form:tablet Route of administration: oral

Alirocumab 75 mg Q2W/up to 150 mg Q2W; Ezetimibe 10 mg

simvastatin DRUG

Pharmaceutical form:tablet Route of administration: oral

Alirocumab 75 mg Q2W/up to 150 mg Q2W; Ezetimibe 10 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (62)

Investigational Site Number 1560027

Beijing, 100029, China

Location

Investigational Site Number 1560043

Beijing, 100034, China

Location

Investigational Site Number 1560039

Beijing, 100053, China

Location

Investigational Site Number 1560012

Beijing, 100730, China

Location

Investigational Site Number 1560018

Beijing, 100730, China

Location

Investigational Site Number 1560006

Changchun, 130021, China

Location

Investigational Site Number 1560020

Changchun, 130021, China

Location

Investigational Site Number 1560023

Changsha, 410011, China

Location

Investigational Site Number 1560030

Fuzhou, 354200, China

Location

Investigational Site Number 1560005

Guangzhou, 510080, China

Location

Investigational Site Number 1560040

Guangzhou, 510080, China

Location

Investigational Site Number 1560025

Guangzhou, 510120, China

Location

Investigational Site Number 1560048

Hangzhou, 310014, China

Location

Investigational Site Number 1560037

Hangzhou, 310015, China

Location

Investigational Site Number 1560008

Hangzhou, 310016, China

Location

Investigational Site Number 1560014

Hohhot, 010017, China

Location

Investigational Site Number 1560016

Jinan, 250013, China

Location

Investigational Site Number 1560044

Lanzhou, 730000, China

Location

Investigational Site Number 1560028

Nanchang, 330006, China

Location

Investigational Site Number 1560045

Nanjing, 210006, China

Location

Investigational Site Number 1560017

Nanjing, 210008, China

Location

Investigational Site Number 1560031

Nanjing, 210011, China

Location

Investigational Site Number 1560035

Nanning, 530031, China

Location

Investigational Site Number 1560029

Shanghai, 200025, China

Location

Investigational Site Number 1560041

Shanghai, 200040, China

Location

Investigational Site Number 1560053

Shanghai, 201199, China

Location

Investigational Site Number 1560009

Shenyang, 110004, China

Location

Investigational Site Number 1560001

Shenyang, 110016, China

Location

Investigational Site Number 1560042

Shenyang, 110016, China

Location

Investigational Site Number 1560036

Shenzhen, 518036, China

Location

Investigational Site Number 1560056

Siping, 136000, China

Location

Investigational Site Number 1560021

Taiyuan, 030001, China

Location

Investigational Site Number 1560002

Tianjin, 300052, China

Location

Investigational Site Number 1560022

Tianjin, 300121, China

Location

Investigational Site Number 1560052

Tianjin, 300140, China

Location

Investigational Site Number 1560055

Wenzhou, 325000, China

Location

Investigational Site Number 1560003

Wuhan, 430022, China

Location

Investigational Site Number 1560004

Xi'an, 710061, China

Location

Investigational Site Number 1560019

Xuzhou, 221002, China

Location

Investigational Site Number 1560054

Yinchuan, 750004, China

Location

Investigational Site Number 1560057

Zhanjiang, 524001, China

Location

Investigational Site Number 3560017

Belagavi, 590010, India

Location

Investigational Site Number 3560001

Gūrgaon, 122001, India

Location

Investigational Site Number 3560003

Hubli, 580021, India

Location

Investigational Site Number 3560010

Kolkata, 700020, India

Location

Investigational Site Number 3560019

Kolkata, 700073, India

Location

Investigational Site Number 3560020

Mangalore, 575002, India

Location

Investigational Site Number 3560006

Mumbai, India

Location

Investigational Site Number 3560007

Nagpur, 440003, India

Location

Investigational Site Number 3560004

Nagpur, 440010, India

Location

Investigational Site Number 3560008

Nagpur, 440012, India

Location

Investigational Site Number 3560016

Nagpur, 440012, India

Location

Investigational Site Number 3560014

New Delhi, 110002, India

Location

Investigational Site Number 3560005

Pune, 411001, India

Location

Investigational Site Number 3560011

Pune, 411001, India

Location

Investigational Site Number 3560013

Surat, 395002, India

Location

Investigational Site Number 3560015

Vijayawada, 520008, India

Location

Investigational Site Number 3560012

Vijaywada, 520002, India

Location

Investigational Site Number 7640004

Bangkok, 10400, Thailand

Location

Investigational Site Number 7640003

Bangkok Noi, 10700, Thailand

Location

Investigational Site Number 7640001

Muang, 50200, Thailand

Location

Investigational Site Number 7640002

Pratumwan, 10400, Thailand

Location

Related Publications (1)

• 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.

  PMID: 31882376 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab; Ezetimibe; Atorvastatin; Rosuvastatin Calcium; Simvastatin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 22, 2016
• Study Start: July 27, 2016
• Primary Completion: August 6, 2018
• Study Completion: August 6, 2018
• Last Updated: September 30, 2019
• Results First Posted: September 30, 2019

Record last verified: 2019-09

Locations

TH (4); CN (41); IN (17)