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

Hypercholesterolemia Clinical Trial

Official title:

A Randomized, Double-Blind Study of the Efficacy and Safety of REGN727 Added-on to Rosuvastatin Versus Ezetimibe Added-on to Rosuvastatin Versus Rosuvastatin Dose Increase in Patients Who Are Not Controlled on Rosuvastatin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01730053
• Other study ID #: R727-CL-1118
• Status: Completed
• Phase: Phase 3
• Start date: November 30, 2012
• Est. completion date: May 31, 2014

Study information

• Verified date: March 2020
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: May 31, 2014
• Est. primary completion date: April 30, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Alirocumab
Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
• Rosuvastatin
Rosuvastatin over-encapsulated tablets orally.
• Ezetimibe
Ezetimibe over-encapsulated tablets orally.
• Placebo
Placebo for alirocumab and ezetimibe.

Locations

Country	Name	City	State
Italy	(2 Locations)	Roma
Mexico	(3 Locations)	Guadalajara
Spain	(2 Locations)	Barcelona
United States	(2 Locations)	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Mexico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	From Baseline to Week 24
Secondary	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).	From Baseline to Week 24
Secondary	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).	From Baseline to Week 12
Secondary	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).	From Baseline to Week 12
Secondary	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.	From Baseline to Week 24
Secondary	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).	From Baseline to Week 24
Secondary	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.	From Baseline to Week 24
Secondary	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).	From Baseline to Week 24
Secondary	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.	From Baseline to Week 24
Secondary	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.	From Baseline to Week 12
Secondary	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.	From Baseline to Week 12
Secondary	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.	From Baseline to Week 12
Secondary	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).	Up to Week 24
Secondary	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 - On-Treatment Analysis	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).	Up to Week 24
Secondary	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 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).	Up to Week 24
Secondary	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	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).	Up to Week 24
Secondary	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.	From Baseline to Week 24
Secondary	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.	From Baseline to Week 24
Secondary	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.	From Baseline to Week 24
Secondary	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.	From Baseline to Week 24
Secondary	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.	From Baseline to Week 12
Secondary	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.	From Baseline to Week 12
Secondary	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.	From Baseline to Week 12
Secondary	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.	From Baseline to Week 12