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

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01288469
First received: February 1, 2011
Last updated: August 21, 2015
Last verified: January 2015
  Purpose

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.

Condition Intervention Phase
Hypercholesterolemia
Drug: Alirocumab
Drug: Placebo (for alirocumab)
Drug: Atorvastatin
Drug: Placebo (for atorvastatin)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed Dose/Dose Regimen, Multicenter Study Evaluating the Efficacy and Safety of SAR236553 When Co-administered With 80 mg of Atorvastatin Over 8 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL (≥2.59 mmol/L) on Atorvastatin 10 mg

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percent Change From Baseline in Calculated LDL-C at Week 8 - On-treatment Analysis [ Time Frame: From Baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    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:
  • Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 8 - On-treatment Analysis [ Time Frame: From baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    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 8 - On-treatment Analysis [ Time Frame: From baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 8 (LOCF) ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: From baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    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).

  • Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 8 - On-treatment Analysis [ Time Frame: From Baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

  • Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 8 - On-treatment Analysis [ Time Frame: From Baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA as for primary endpoint.


Enrollment: 92
Study Start Date: January 2011
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo + Atorvastatin 80 mg
Placebo (for alirocumab) subcutaneous (SC) administration every 2 weeks (Q2W) in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Drug: Placebo (for alirocumab)
One SC injection in the abdomen only.
Drug: Atorvastatin
Over-encapsulated tablet orally once daily in the evening with dinner.
Experimental: Alirocumab + Atorvastatin 10 mg
Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks.
Drug: Alirocumab
One subcutaneous (SC) injection in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
Drug: Atorvastatin
Over-encapsulated tablet orally once daily in the evening with dinner.
Drug: Placebo (for atorvastatin)
One over-encapsulated tablet of placebo for atorvastatin orally once daily in the evening with dinner.
Experimental: Alirocumab + Atorvastatin 80 mg
Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Drug: Alirocumab
One subcutaneous (SC) injection in the abdomen only.
Other Names:
  • SAR236553
  • REGN727
Drug: Atorvastatin
Over-encapsulated tablet orally once daily in the evening with dinner.

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

- 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 with primary hypercholesterolemia if they are likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy

OR

- Participants with primary hypercholesterolemia treated with stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening and likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit.

Exclusion criteria:

  1. LDL-C < 100 mg/dL (< 2.59 mmol/L) at Week -1 (V1):

    • After the run-in period on atorvastatin 10 mg 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 the screening period, or drug naive participants.

    OR

    • At the first visit for participants who are being treated with atorvastatin 10 mg at stable dose for at least 6 weeks prior to screening visit.
  2. Participants not previously instructed on a cholesterol-lowering diet.
  3. Participants with type 1 diabetes.
  4. Participants with type 2 diabetes treated with insulin.
  5. Participants with type 2 diabetes and with an HbA1c ≥ 8.5% at screening visit (considered poorly controlled).
  6. Laboratory findings measured before randomization:

    • Triglycerides (TG) > 350 mg/dL (> 3.95 mmol/L) at screening visit.
    • Positive serum or urine pregnancy test in females of childbearing potential.
  7. Pregnant or breast-feeding women.
  8. Women of childbearing potential with no effective contraceptive method.

The above information is not intended to contain all considerations relevant to a Participant's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01288469

Locations
United States, Arizona
Investigational Site Number 840616
Mesa, Arizona, United States, 85206
Investigational Site Number 840601
Tucson, Arizona, United States, 85710
United States, California
Investigational Site Number 840610
Los Angeles, California, United States, 90057
Investigational Site Number 840608
Newport Beach, California, United States, 92660
United States, Florida
Investigational Site Number 840603
Doral, Florida, United States, 33166
Investigational Site Number 840611
Jacksonville, Florida, United States, 32223
Investigational Site Number 840618
Jupiter, Florida, United States, 33458
Investigational Site Number 840612
Miami, Florida, United States, 33138
Investigational Site Number 840614
Miami, Florida, United States, 33138
Investigational Site Number 840607
St. Petersburg, Florida, United States, 33609
United States, Illinois
Investigational Site Number 840605
Chicago, Illinois, United States, 60610
Investigational Site Number 840619
Chicago, Illinois, United States, 60610
United States, New Jersey
Investigational Site Number 840604
Edison, New Jersey, United States, 08817
United States, New York
Investigational Site Number 840606
Rochester, New York, United States, 14609
United States, Ohio
Investigational Site Number 840615
Cincinnati, Ohio, United States, 45219
Investigational Site Number 840617
Cincinnati, Ohio, United States, 45219
United States, Oregon
Investigational Site Number 840602
Eugene, Oregon, United States, 97404
United States, Virginia
Investigational Site Number 840621
Richmond, Virginia, United States, 23227
United States, Washington
Investigational Site Number 840609
Olympia, Washington, United States, 98502
United States, Wisconsin
Investigational Site Number 840613
Oregon, Wisconsin, United States, 53575
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01288469     History of Changes
Other Study ID Numbers: DFI11566  U1111-1117-9994 
Study First Received: February 1, 2011
Results First Received: August 21, 2015
Last Updated: August 21, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
10020603

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin Calcium
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016