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Evaluation of SAR236553 (REGN727) When Co-administered With Atorvastatin in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL

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: December 12, 2012
Last verified: December 2012
History of Changes
  Purpose

Primary Objective:

o To evaluate the effect of 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 patients with LDL-C ≥ 100mg/dL (≥ 2.59 mmol/L) on atorvastatin 10 mg.

Secondary Objectives:

  • To evaluate the effects of SAR236553 (REGN727) 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 SAR236553 (REGN727) when co-administered with a high dose of atorvastatin (80 mg) versus atorvastatin 10 mg.
  • To evaluate the safety and tolerability of SAR236553 (REGN727) when co-administered with 2 different doses of atorvastatin.
  • To evaluate the development of anti-SAR236553 (REGN727) antibodies.
  • To evaluate the pharmacokinetics of SAR236553 (REGN727).

Condition Intervention Phase
Hypercholesterolemia
 Drug: SAR236553 (REGN727)
Drug: SAR236553 (REGN727) matching placebo
Drug: atorvastatin
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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:

MedlinePlus related topics: Cholesterol
U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percent change in calculated low-density lipoprotein cholesterol (LDL-C) [ Time Frame: from baseline to Week 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Absolute change in calculated low-density lipoprotein cholesterol (LDL-C) [ Time Frame: from baseline to Week 8 ] [ 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) [ Time Frame: at week 8 ] [ 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) [ Time Frame: at week 8 ] [ Designated as safety issue: No ]
  • Percent change in Total Cholesterol (TC) [ Time Frame: from baseline to Week 8 ] [ Designated as safety issue: No ]
  • Percent change in Triglycerides (TG) [ Time Frame: from baseline to Week 8 ] [ Designated as safety issue: No ]
  • Percent change in High-density lipoprotein cholesterol (HDL-C) [ Time Frame: from baseline to Week 8 ] [ Designated as safety issue: No ]

Enrollment: 92
Study Start Date: January 2011
Study Completion Date: September 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR236553 (REGN727) + atorvastatin 80mg

SAR236553 (REGN727), at dose 1 regimen, will be administered in one subcutaneous (SC) injection of 1 mL in the abdomen every two weeks. Atorvastatin will be administered once daily at a stable dose of :

  • 10 mg as background therapy during the run-in period,
  • 80 mg (two over-encapsulated tablets of 40 mg) during the double-blind treatment period.
 Drug: SAR236553 (REGN727)

Pharmaceutical form:solution for injection

Route of administration: subcutaneous

Drug: atorvastatin

Pharmaceutical form:tablet

Route of administration: oral
Placebo Comparator: SAR236553 (REGN727) matching placebo + atorvastatin 80 mg

SAR236553 (REGN727) matching placebo, at dose 1 regimen, will be administered in one subcutaneous (SC) injection of 1 mL in the abdomen every two weeks. Atorvastatin will be administered once daily at a stable dose of :

  • 10 mg as background therapy during the run-in period,
  • 80 mg (two over-encapsulated tablets of 40 mg) during the double-blind treatment period.
 Drug: SAR236553 (REGN727) matching placebo

Pharmaceutical form:solution for injection

Route of administration: subcutaneous

Drug: atorvastatin

Pharmaceutical form:tablet

Route of administration: oral
Experimental: SAR236553 (REGN727) + atorvastatin 10 mg

SAR236553 (REGN727), at dose 1 regimen, will be administered in one subcutaneous (SC) injection of 1 mL in the abdomen every two weeks. Atorvastatin will be administered once daily at a stable dose of :

  • 10 mg as background therapy during the run-in period,
  • 10 mg (1 over-encapsulated atorvastatin 10 mg tablet + 1 matching placebo tablet) during the double-blind treatment period.
 Drug: SAR236553 (REGN727)

Pharmaceutical form:solution for injection

Route of administration: subcutaneous

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 at stable dose for at least 6 weeks prior to screening, the study participation will 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 patients 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 patients the study participation will be approximately 23 weeks with a screening period of 7 weeks (including a run-in period 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patients (patients 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 period, or drug naive patients) with primary hypercholesterolemia likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the run-in period on atorvastatin therapy (Week -1).

OR

  • Patients with primary hypercholesterolemia treated with stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening period and likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit (Week -1).

Exclusion criteria:

  • LDL-C < 100 mg/dL (< 2.59 mmol/L) at Week -1 (V1):
  • After the run-in period on atorvastatin 10 mg for patients 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 patients.

OR

  • At the first visit for patients who are being treated with atorvastatin 10 mg at stable dose for at least 6 weeks prior to screening visit Week -1.
  • Patients not previously instructed on a cholesterol-lowering diet.
  • Patients with type 1 diabetes.
  • Patients with type 2 diabetes treated with insulin.
  • Patients with type 2 diabetes and with an HbA1c ≥ 8.5% at Week -7 or Week -1 (considered poorly controlled).

  • Laboratory findings measured before randomization:

    • Triglycerides (TG) > 350 mg/dL (> 3.95 mmol/L) at Week -7 or Week -1.
    • Positive serum or urine pregnancy test in females of childbearing potential.
  • Pregnant or breast-feeding women.
  • 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
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 840614
Miami, Florida, United States, 33138
Investigational Site Number 840612
Miami, Florida, United States, 33138
Investigational Site Number 840607
St. Petersburg, Florida, United States, 33609
United States, Illinois
Investigational Site Number 840619
Chicago, Illinois, United States, 60610
Investigational Site Number 840605
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 840617
Cincinnati, Ohio, United States, 45219
Investigational Site Number 840615
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

No publications provided by Sanofi

Additional 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
Last Updated: December 12, 2012
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
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
 Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 22, 2013