Study of Alirocumab (REGN727/SAR236553) added-on to Rosuvastatin Versus Other Lipid Modifying Treatments (LMT) (ODYSSEY OPTIONS II)

Regeneron Pharmaceuticals305 enrolled

Overview

To evaluate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab (REGN727/SAR236553) as an add-on therapy to other LMT in patients with hypercholesterolemia at high cardiovascular (CV) risk.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

305

Conditions

Hypercholesterolemia

Interventions

AlirocumabDRUG

Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

RosuvastatinDRUG

Rosuvastatin over-encapsulated tablets orally.

EzetimibeDRUG

Ezetimibe over-encapsulated tablets orally.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients with LDL-C greater than or equal to 70 mg/dL at the screening visit and who are not adequately controlled with a stable daily dose of rosuvastatin, with or without other LMT. OR 2. Patients with screening LDL-C greater than or equal to 100 mg/dL who are not adequately controlled with a stable daily dose of rosuvastatin before the screening visit, with or without other LMT. Exclusion Criteria: 1. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented cardiovascular disease (CVD) 2. LDL-C less than 100 mg/dL at the screening visit in patients without history of documented coronary heart disease (CHD) or non-CHD CVD, but with other risk factors 3. Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping) 4. Recent (within 3 months prior to the screening visit) myocardial infarction (MI), unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease 5. Newly diagnosed (within 3 months prior to randomization visit) or poorly controlled diabetes 6. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins (The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial).

Locations (93)

Outcomes

Primary Outcomes

Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis

Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Time frame: From Baseline to Week 24

Secondary Outcomes

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (ie. up to 21 days after last injection or 3 days after the last capsule \[whatever rosuvastatin or ezetimibe\], whichever came first) (on-treatment analysis).

Time frame: From Baseline to Week 24

Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment (ITT analysis).

Time frame: From Baseline to Week 12

Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis

Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule \[whatever rosuvastatin or ezetimibe\], whichever came first) (on-treatment analysis).

Time frame: From Baseline to Week 12

Data from ClinicalTrials.gov

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Placebo for alirocumab and ezetimibe.

Unnamed facility

Chandler, Arizona, United States

Unnamed facility

Tucson, Arizona, United States

Unnamed facility

Anaheim, California, United States

Unnamed facility

Beverly Hills, California, United States

Unnamed facility

Fair Oaks, California, United States

Unnamed facility

Newport Beach, California, United States

Unnamed facility

Northridge, California, United States

Unnamed facility

Sacramento, California, United States

Unnamed facility

Walnut Creek, California, United States

Unnamed facility

Milford, Connecticut, United States

...and 83 more locations

Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (ie. up to 21 days after last injection or 3 days after the last capsule \[whatever rosuvastatin or ezetimibe\], whichever came first).

Time frame: From Baseline to Week 24

Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule \[whatever rosuvastatin or ezetimibe\], whichever came first).

Time frame: From Baseline to Week 24

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percent Change From Baseline in Apo B at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 12

Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 12

Percent Change From Baseline in Total-C at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 12

Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis

Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).

Time frame: Up to Week 24

Calculated LDL-C values were obtained from Friedewald formula. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule \[whatever rosuvastatin or ezetimibe\], whichever came first (on-treatment analysis).

Time frame: Up to Week 24

Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis

Time frame: Up to Week 24

Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis

Time frame: Up to Week 24

Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis

Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis

Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 24

Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis

Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 12

Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 12

Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis

Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 12

Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Time frame: From Baseline to Week 12