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
Overview
- Phase
- Phase 3
- Intervention
- Placebo for alirocumab
- Conditions
- Hypercholesterolemia
- Sponsor
- Sanofi
- Enrollment
- 615
- Locations
- 62
- Primary Endpoint
- Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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).
Intervention: Placebo for alirocumab
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).
Intervention: ezetimibe
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).
Intervention: atorvastatin
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).
Intervention: rosuvastatin
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).
Intervention: simvastatin
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.
Intervention: Alirocumab
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.
Intervention: placebo for ezetimibe
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.
Intervention: atorvastatin
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.
Intervention: rosuvastatin
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.
Intervention: simvastatin
Outcomes
Primary Outcomes
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis
Time Frame: From Baseline to Week 24
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).
Secondary Outcomes
- 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 24: On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Apolipoprotein B 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)
- Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Analysis(From Baseline to Week 24)
- Percentage of Participants Reaching Calculated Low Density Lipoprotein Cholesterol <70 mg/dL (1.81 mmol/L) at Week 24: ITT Analysis(Up to Week 24)
- Percent Change From Baseline in Fasting Triglycerides at Week 12: ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24: ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12: ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Total Cholesterol at Week 12: ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 24: ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 24: ITT Analysis(From Baseline 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(Up to Week 24)
- Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Analysis(From Baseline to Week 24)
- Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis(From Baseline to Week 12)
- Percent Change From Baseline in Apolipoprotein A-1 at Week 12 : ITT Analysis(From Baseline to Week 12)