Evaluation of Alirocumab Versus Ezetimibe on Top of Statin in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT02715726
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 615
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ezetimibe 10 mg Placebo for alirocumab 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). Ezetimibe 10 mg atorvastatin 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). Alirocumab 75 mg Q2W/up to 150 mg Q2W placebo for ezetimibe 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. Alirocumab 75 mg Q2W/up to 150 mg Q2W simvastatin 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. Ezetimibe 10 mg ezetimibe 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). Ezetimibe 10 mg rosuvastatin 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). Ezetimibe 10 mg simvastatin 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). Alirocumab 75 mg Q2W/up to 150 mg Q2W Alirocumab 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. Alirocumab 75 mg Q2W/up to 150 mg Q2W atorvastatin 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. Alirocumab 75 mg Q2W/up to 150 mg Q2W rosuvastatin 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.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: Intent-to-treat (ITT) Analysis 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 Outcome Measures
Name Time Method Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis From Baseline to Week 24 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).
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: ITT Analysis From Baseline to Week 12 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.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Analysis From Baseline to Week 12 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.
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol at Week 12: On-Treatment Analysis From Baseline to Week 12 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).
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Apolipoprotein B at Week 24: On-Treatment Analysis From Baseline to Week 24 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).
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 24: On-Treatment Analysis From Baseline to Week 24 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).
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Analysis From Baseline to Week 12 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.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Analysis From Baseline to Week 24 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.
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 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.
Percent Change From Baseline in Fasting Triglycerides at Week 12: ITT Analysis From Baseline to Week 12 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.
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24: ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12: ITT Analysis From Baseline to Week 12 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.
Percent Change From Baseline in Total Cholesterol at Week 12: ITT Analysis From Baseline to Week 12 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.
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 24: ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 24: ITT Analysis From Baseline to Week 24 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.
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 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).
Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis From Baseline to Week 12 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.
Percent Change From Baseline in Apolipoprotein A-1 at Week 12 : ITT Analysis From Baseline to Week 12 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.
Trial Locations
- Locations (62)
Investigational Site Number 1560018
🇨🇳Beijing, China
Investigational Site Number 1560008
🇨🇳Hangzhou, China
Investigational Site Number 1560009
🇨🇳Shenyang, China
Investigational Site Number 1560042
🇨🇳Shenyang, China
Investigational Site Number 1560016
🇨🇳Jinan, China
Investigational Site Number 1560053
🇨🇳Shanghai, China
Investigational Site Number 1560036
🇨🇳Shenzhen, China
Investigational Site Number 1560031
🇨🇳Nanjing, China
Investigational Site Number 1560035
🇨🇳Nanning, China
Investigational Site Number 1560021
🇨🇳Taiyuan, China
Investigational Site Number 1560056
🇨🇳Siping, China
Investigational Site Number 1560002
🇨🇳Tianjin, China
Investigational Site Number 1560022
🇨🇳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 3560006
🇮🇳Mumbai, India
Investigational Site Number 3560019
🇮🇳Kolkata, India
Investigational Site Number 3560004
🇮🇳Nagpur, India
Investigational Site Number 3560010
🇮🇳Kolkata, India
Investigational Site Number 3560012
🇮🇳Vijaywada, India
Investigational Site Number 3560014
🇮🇳New Delhi, India
Investigational Site Number 7640004
🇹🇭Bangkok, Thailand
Investigational Site Number 7640002
🇹🇭Pratumwan, Thailand
Investigational Site Number 1560028
🇨🇳Nanchang, China
Investigational Site Number 1560029
🇨🇳Shanghai, China
Investigational Site Number 1560041
🇨🇳Shanghai, China
Investigational Site Number 1560044
🇨🇳Lanzhou, China
Investigational Site Number 1560001
🇨🇳Shenyang, China
Investigational Site Number 1560052
🇨🇳Tianjin, China
Investigational Site Number 1560014
🇨🇳Hohhot, China
Investigational Site Number 1560027
🇨🇳Beijing, China
Investigational Site Number 1560048
🇨🇳Hangzhou, China
Investigational Site Number 3560017
🇮🇳Belgaum, India
Investigational Site Number 3560001
🇮🇳Gurgaon, India
Investigational Site Number 1560054
🇨🇳Yinchuan, China
Investigational Site Number 1560057
🇨🇳Zhanjiang, China
Investigational Site Number 3560007
🇮🇳Nagpur, India
Investigational Site Number 3560011
🇮🇳Pune, India
Investigational Site Number 3560003
🇮🇳Hubli, India
Investigational Site Number 7640001
🇹🇭Muang, Thailand
Investigational Site Number 3560008
🇮🇳Nagpur, India
Investigational Site Number 3560016
🇮🇳Nagpur, India
Investigational Site Number 3560005
🇮🇳Pune, India
Investigational Site Number 3560015
🇮🇳Vijayawada, India
Investigational Site Number 3560013
🇮🇳Surat, India
Investigational Site Number 7640003
🇹🇭Bangkok-Noi, Thailand
Investigational Site Number 1560039
🇨🇳Beijing, China
Investigational Site Number 1560043
🇨🇳Beijing, China
Investigational Site Number 1560006
🇨🇳Changchun, China
Investigational Site Number 1560012
🇨🇳Beijing, 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 1560040
🇨🇳Guangzhou, China
Investigational Site Number 1560025
🇨🇳Guangzhou, China
Investigational Site Number 1560037
🇨🇳Hangzhou, China
Investigational Site Number 3560020
🇮🇳Mangalore, India
Investigational Site Number 1560017
🇨🇳Nanjing, China
Investigational Site Number 1560045
🇨🇳Nanjing, China