Efficacy and Safety of REGN727/SAR236553 added-on to Atorvastatin versus Ezetimibe added-on to Atorvastatin versus Atorvastatin dose increase versus switch to Rosuvastatin in patients who are not controlled on Atorvastati

Phase 1

• Conditions: Patients with Non-familial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH) at high CV risk who are not adequately controlled with atorvastatin (20mg or 40mg) with or without other lipid-modifying therapy (LMT) (excluding EZE); MedDRA version: 17.0 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2012-002344-24-GB
• Lead Sponsor: Regeneron Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-01-22
• Study Completion: 2014-05-06
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 355

Inclusion Criteria

1. A patient must meet either 1a or 1b to be eligible for inclusion in the study:
a. Patients with screening (visit 1) LDL-C =70 mg/dL (1.81 mmol/L) who are not adequately controlled with a 20 mg or 40 mg stable daily dose of atorvastatin for at least 4 weeks before the screening visit (visit 1), with or without other LMT (excluding EZE). Patients with heFH* or non-FH must also have a history of documented CHD (defined below), or non-CHD CVD (defined below), or diabetes mellitus with target organ damage.
OR
b. Patients with screening (visit 1) LDL-C =100 mg/dL (2.59 mmol/L) who are not adequately controlled with a 20 mg or 40 mg daily dose of atorvastatin for at least 4 weeks before the screening visit (visit 1), with or without other LMT (excluding EZE). Patients must also have heFH*, or have non-FH, without CHD or non-CHD CVD, but with a calculated 10-year fatal CVD risk SCORE =5%, or with moderate CKD, or with diabetes mellitus but no target organ damage.
Note: Details for the inclusion criteria are provided below.
2. Provide signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 52

Exclusion Criteria

LDL-C <70 mg/dL (<1.81 mmol/L) in patients with CVD
LDL-C <100 mg/dL (<2.59 mmol/L) in patients without CVD, but with other risk factors
LDL-C >250 mg/dL or TG >400 mg/dL
Homozygous FH or patients receiving plasmapheresis
CV event within 3 months prior to screening
NYHA Class III or IV heart failure
History of hemorrhagic stroke
Uncontrolled endocrine disease known to influence serum lipids
Any clinically significant abnormality that in the judgment of the investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, patients with short life expectancy, patients who cannottolerate subcutaneous injections.
Use of ezetimibe or red yeast rice products within 4 weeks of screening
Use of systemic corticosteroids or use of fibrates, other than fenofibrate within 6 weeks of the screening
eGFR <30 mL/min/1.73m2
ALT or AST aminotransferase >3 x upper limit of normal (ULN)
CPK >3 x ULN
TSH < lower limit of normal (LLN)
Hypersensitivity to monoclonal antibody therapeutics
Pregnant or breast-feeding women
Women of childbearing potential with no effective contraceptive method of birth control

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified