Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) When Co-administered With High Dose of Atorvastatin in Patients With Primary Hypercholesterolemia

Phase 2

Completed

• Conditions: Hypercholesterolemia
• Interventions: Drug: Placebo (for alirocumab); Drug: Alirocumab; Drug: Atorvastatin; Drug: Placebo (for atorvastatin)

• Registration Number: NCT01288469
• Lead Sponsor: Sanofi

Brief Summary

Primary Objective:

To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels compared with placebo when co-administered with 80 mg of atorvastatin after 8 weeks of treatment in participants with LDL-C ≥ 100mg/dL (≥ 2.59 mmol/L) on atorvastatin 10 mg.

Secondary Objectives:

* To evaluate the effects of alirocumab on other lipid levels in comparison with placebo, when co-administered with 80 mg of atorvastatin after 8 weeks of treatment.

* To evaluate the efficacy of alirocumab when co-administered with a high dose of atorvastatin (80 mg) versus atorvastatin 10 mg.

* To evaluate the safety and tolerability of alirocumab when co-administered with 2 different doses of atorvastatin.

* 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 patient at screening:

* For participants receiving atorvastatin 10 mg at stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 17 weeks including a screening period of 1 week, a double-blind treatment period of 8 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 for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 23 weeks with a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg of 6 weeks, a double-blind treatment period of 8 weeks and a follow-up period of 8 weeks.

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-02-01
• Study First Submitted QC: 2011-02-01
• Study First Posted: 2011-02-02
• Primary Completion: 2011-09
• Study Completion: 2011-09
• Disposition First Submitted: 2012-12-12
• Disposition First Submitted QC: 2012-12-12
• Disposition First Posted: 2012-12-17
• Status Verified: 2015-01
• Results First Submitted: 2015-08-21
• Results First Submitted QC: 2015-08-21
• Last Update Submitted: 2015-08-21
• Results First Posted: 2015-09-24
• Last Update Posted: 2015-09-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alirocumab + Atorvastatin 10 mg	Placebo (for atorvastatin)	Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks.
Placebo + Atorvastatin 80 mg	Placebo (for alirocumab)	Placebo (for alirocumab) subcutaneous (SC) administration every 2 weeks (Q2W) in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Alirocumab + Atorvastatin 80 mg	Atorvastatin	Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Placebo + Atorvastatin 80 mg	Atorvastatin	Placebo (for alirocumab) subcutaneous (SC) administration every 2 weeks (Q2W) in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Alirocumab + Atorvastatin 10 mg	Alirocumab	Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks.
Alirocumab + Atorvastatin 10 mg	Atorvastatin	Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks.
Alirocumab + Atorvastatin 80 mg	Alirocumab	Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Calculated LDL-C at Week 8 - On-treatment Analysis	From Baseline to Week 8 (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 investigational product (IP) injection up to 21 days after last IP injection (on-treatment analysis). Missing Week 8 data were imputed by last observation carried forward \[LOCF\] method.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Total Cholesterol, Fasting Triglycerides, Non-high-Density Lipoprotein Cholesterol (Non-HDL-C), Apolipoprotein B (Apo-B) and Lipoprotein(a) at Week 8 - On-treatment Analysis	From baseline to Week 8 (LOCF)	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range).
Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 8 - On-treatment Analysis	From baseline to Week 8 (LOCF)	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 8 - On-treatment Analysis	From Baseline to Week 8 (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 (mmol/L) at Week 8 - On-treatment Analysis	From baseline to Week 8 (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 8 - On-treatment Analysis	Week 8 (LOCF)
Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 8 - On-treatment Analysis	From Baseline to Week 8 (LOCF)	Adjusted LS means and standard errors were estimated using the same ANCOVA as for primary endpoint.

Trial Locations

Locations (20)

Investigational Site Number 840619; 🇺🇸 Chicago, Illinois, United States

Investigational Site Number 840621; 🇺🇸 Richmond, Virginia, United States

Investigational Site Number 840602; 🇺🇸 Eugene, Oregon, United States

Investigational Site Number 840609; 🇺🇸 Olympia, Washington, United States

Investigational Site Number 840606; 🇺🇸 Rochester, New York, United States

Investigational Site Number 840604; 🇺🇸 Edison, New Jersey, United States

Investigational Site Number 840613; 🇺🇸 Oregon, Wisconsin, United States

Investigational Site Number 840616; 🇺🇸 Mesa, Arizona, United States

Investigational Site Number 840601; 🇺🇸 Tucson, Arizona, United States

Investigational Site Number 840610; 🇺🇸 Los Angeles, California, United States

Investigational Site Number 840603; 🇺🇸 Doral, Florida, United States

Investigational Site Number 840618; 🇺🇸 Jupiter, Florida, United States

Investigational Site Number 840612; 🇺🇸 Miami, Florida, United States

Investigational Site Number 840611; 🇺🇸 Jacksonville, Florida, United States

Investigational Site Number 840608; 🇺🇸 Newport Beach, California, United States

Investigational Site Number 840614; 🇺🇸 Miami, Florida, United States

Investigational Site Number 840607; 🇺🇸 St. Petersburg, Florida, United States

Investigational Site Number 840605; 🇺🇸 Chicago, Illinois, United States

Investigational Site Number 840615; 🇺🇸 Cincinnati, Ohio, United States

Investigational Site Number 840617; 🇺🇸 Cincinnati, Ohio, United States