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

Sanofi

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia

Treatments: Drug: atorvastatin; Drug: ezetimibe; Drug: Alirocumab; Drug: placebo for ezetimibe; Drug: rosuvastatin; Drug: Placebo for alirocumab; Drug: simvastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02715726

EFC13889

U1111-1150-8859 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 615 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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615 participants in 2 patient groups

Ezetimibe 10 mg

Active Comparator group

Description:

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).

Treatment:

Drug: simvastatin

Drug: Placebo for alirocumab

Drug: atorvastatin

Drug: ezetimibe

Drug: rosuvastatin

Alirocumab 75 mg Q2W/up to 150 mg Q2W

Experimental group

Description:

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.

Treatment:

Drug: simvastatin

Drug: atorvastatin

Drug: Alirocumab

Drug: placebo for ezetimibe

Drug: rosuvastatin