Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia and LDL-cholesterol on Stable Atorvastatin Therapy

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01288443
First received: February 1, 2011
Last updated: January 22, 2015
Last verified: January 2015
  Purpose

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 patients with LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) on ongoing stable atorvastatin therapy.

Secondary Objective:

  • 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.

Condition Intervention Phase
Hypercholesterolemia
Drug: alirocumab
Drug: placebo (for alirocumab)
Drug: atorvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of Five Doses and Two Dose Regimens of SAR236553 Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL (≥ 2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy.

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percent change in calculated low-density lipoprotein cholesterol (LDL-C) at Week 12 [ Time Frame: from baseline (randomization) to Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Absolute change in calculated low-density lipoprotein cholesterol (LDL-C) at Week 12 [ Time Frame: from baseline (randomization) to Week 12 ] [ Designated as safety issue: No ]
  • Proportion of patients achieving an low-density lipoprotein cholesterol (LDL-C) level lower than 100mg/dL (2.59 mmol/L) at Week 12 [ Time Frame: from baseline (randomization) to Week 12 ] [ Designated as safety issue: No ]
  • Proportion of patients achieving an low-density lipoprotein cholesterol (LDL-C) level lower than 70mg/dL (1.81 mmol/L) at Week 12 [ Time Frame: from baseline (randomization) to Week 12 ] [ Designated as safety issue: No ]
  • Percent change in Total Cholesterol (TC) at Week 12 [ Time Frame: from baseline (randomization) to Week 12 ] [ Designated as safety issue: No ]
  • Percent change in Triglycerides (TG) at Week 12 [ Time Frame: from baseline (randomization) to Week 12 ] [ Designated as safety issue: No ]
  • Percent change in density lipoprotein cholesterol at Week 12 [ Time Frame: from baseline (randomization) to Week 12 ] [ Designated as safety issue: No ]

Enrollment: 183
Study Start Date: January 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alirocumab dose 1
Two injections of alirocumab dose 1 through subcutaneous (SC) administration + atorvastatin orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy
Drug: alirocumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection in the abdomen only (i.e. no rotation of the injection site)

Other Names:
  • SAR236553
  • REGN727
Drug: atorvastatin

Pharmaceutical form: tablet

Route of administration: oral

Experimental: Alirocumab dose 2
Two injections of alirocumab dose 2 through subcutaneous (SC) administration + atorvastatin orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy
Drug: alirocumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection in the abdomen only (i.e. no rotation of the injection site)

Other Names:
  • SAR236553
  • REGN727
Drug: atorvastatin

Pharmaceutical form: tablet

Route of administration: oral

Experimental: Alirocumab dose 3
Two injections of alirocumab dose 3 through subcutaneous (SC) administration + atorvastatin orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy
Drug: alirocumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection in the abdomen only (i.e. no rotation of the injection site)

Other Names:
  • SAR236553
  • REGN727
Drug: atorvastatin

Pharmaceutical form: tablet

Route of administration: oral

Placebo Comparator: Placebo
Two injections of placebo (for alirocumab) through subcutaneous (SC) administration + atorvastatin orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy
Drug: placebo (for alirocumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection in the abdomen only (i.e. no rotation of the injection site)

Drug: atorvastatin

Pharmaceutical form: tablet

Route of administration: oral

Experimental: Alirocumab dose 4 alternating placebo
Two injections of alirocumab dose 4 through subcutaneous (SC) administration alternating with matching placebo administration + atorvastatin orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy
Drug: alirocumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection in the abdomen only (i.e. no rotation of the injection site)

Other Names:
  • SAR236553
  • REGN727
Drug: placebo (for alirocumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection in the abdomen only (i.e. no rotation of the injection site)

Drug: atorvastatin

Pharmaceutical form: tablet

Route of administration: oral

Experimental: Alirocumab dose 5 alternating placebo
Two injections of alirocumab dose 5 through subcutaneous (SC) administration alternating with matching placebo administration + atorvastatin orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy
Drug: alirocumab

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection in the abdomen only (i.e. no rotation of the injection site)

Other Names:
  • SAR236553
  • REGN727
Drug: placebo (for alirocumab)

Pharmaceutical form: solution for injection

Route of administration: subcutaneous injection in the abdomen only (i.e. no rotation of the injection site)

Drug: atorvastatin

Pharmaceutical form: tablet

Route of administration: oral


Detailed Description:

The duration of study participation will depend on the status of the patient at screening:

  • For patients receiving atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose for at least 6 weeks prior to screening, the study participation will 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 patients 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 patients, the study participation will 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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patients with primary hypercholesterolemia 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 period or drug naïve patients 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

  • Patients with primary hypercholesterolemia treated with atorvastatin at stable dose of 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period and likely to have 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):

    - After the run-in period on atorvastatin (10 mg, 20 mg, or 40 mg) for patients 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 the screening , or drug naive patients.

    OR

    - At the first visit for patients who are being treated with stable dose of atorvastatin (10 mg, 20 mg, or 40 mg) for at least 6 weeks prior to screening.

  2. Patients not previously instructed on a cholesterol-lowering diet.
  3. Patients with type 1 diabetes.
  4. Patients with type 2 diabetes treated with insulin.
  5. Patients 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 patient'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: NCT01288443

  Show 38 Study Locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01288443     History of Changes
Other Study ID Numbers: DFI11565, U1111-1116-5252
Study First Received: February 1, 2011
Last Updated: January 22, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015