Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT01288443
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
* To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) on ongoing stable atorvastatin therapy.
Secondary Objectives:
* To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo
* To evaluate the safety and tolerability of alirocumab
* To evaluate the development of anti-alirocumab antibodies
* To evaluate the pharmacokinetics of alirocumab
- Detailed Description
The duration of study participation depended on the status of the participant at screening:
* For participants receiving atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 21 weeks including a screening period of 1 week, a double-blind treatment period of 12 weeks and a follow-up period of 8 weeks.
* For participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 27 weeks including a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose of 6 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 8 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 183
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Alirocumab 50 mg Q2W Alirocumab Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Alirocumab 50 mg Q2W Atorvastatin Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Placebo Q2W Placebo (for alirocumab) Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose. Alirocumab 200 mg Q4W Placebo (for alirocumab) Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose. Alirocumab 300 mg Q4W Placebo (for alirocumab) Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose. Placebo Q2W Atorvastatin Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose. Alirocumab 100 mg Q2W Alirocumab Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Alirocumab 100 mg Q2W Atorvastatin Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Alirocumab 150 mg Q2W Atorvastatin Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Alirocumab 150 mg Q2W Alirocumab Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Alirocumab 200 mg Q4W Alirocumab Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose. Alirocumab 200 mg Q4W Atorvastatin Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose. Alirocumab 300 mg Q4W Alirocumab Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose. Alirocumab 300 mg Q4W Atorvastatin Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis Baseline to Week 12 (LOCF) Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first study drug injection up to 21 days after last study drug injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method.
- Secondary Outcome Measures
Name Time Method Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis Baseline to Week 12 (LOCF) Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis Baseline to Week 12 (LOCF) Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis Week 12 (LOCF) Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis Baseline to Week 12 (LOCF) Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis Baseline to Week 12 (LOCF) Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range).
Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis Baseline to Week 12 (LOCF) Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.
Trial Locations
- Locations (38)
Investigational Site Number 840525
🇺🇸Tempe, Arizona, United States
Investigational Site Number 840521
🇺🇸Bristol, Tennessee, United States
Investigational Site Number 840516
🇺🇸Los Angeles, California, United States
Investigational Site Number 840534
🇺🇸Westlake Village, California, United States
Investigational Site Number 840509
🇺🇸Newport Beach, California, United States
Investigational Site Number 840528
🇺🇸Mission Viejo, California, United States
Investigational Site Number 840523
🇺🇸Palm Springs, California, United States
Investigational Site Number 840530
🇺🇸Colorado Springs, Colorado, United States
Investigational Site Number 840514
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 840504
🇺🇸Aventura, Florida, United States
Investigational Site Number 840519
🇺🇸Aventura, Florida, United States
Investigational Site Number 840539
🇺🇸Jupiter, Florida, United States
Investigational Site Number 840520
🇺🇸Pembroke Pines, Florida, United States
Investigational Site Number 840524
🇺🇸Ponte Vedra, Florida, United States
Investigational Site Number 840502
🇺🇸Miami, Florida, United States
Investigational Site Number 840536
🇺🇸Port Orange, Florida, United States
Investigational Site Number 840507
🇺🇸St. Petersburg, Florida, United States
Investigational Site Number 840527
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840506
🇺🇸Evansville, Indiana, United States
Investigational Site Number 840529
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840515
🇺🇸Wichita, Kansas, United States
Investigational Site Number 840532
🇺🇸Madisonville, Kentucky, United States
Investigational Site Number 840535
🇺🇸Auburn, Maine, United States
Investigational Site Number 840512
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number 840503
🇺🇸Brockton, Massachusetts, United States
Investigational Site Number 840505
🇺🇸Edison, New Jersey, United States
Investigational Site Number 840511
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 840508
🇺🇸Raleigh, North Carolina, United States
Investigational Site Number 840538
🇺🇸Rochester, New York, United States
Investigational Site Number 840526
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 840522
🇺🇸Statesville, North Carolina, United States
Investigational Site Number 840510
🇺🇸Lyndhurst, Ohio, United States
Investigational Site Number 840533
🇺🇸Tulsa, Oklahoma, United States
Investigational Site Number 840531
🇺🇸Bountiful, Utah, United States
Investigational Site Number 840517
🇺🇸Norfolk, Virginia, United States
Investigational Site Number 840518
🇺🇸Richmond, Virginia, United States
Investigational Site Number 840513
🇺🇸Olympia, Washington, United States
Investigational Site Number 840537
🇺🇸Eugene, Oregon, United States