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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01730053




Registration number
NCT01730053
Ethics application status
Date submitted
9/11/2012
Date registered
21/11/2012
Date last updated
7/04/2020

Titles & IDs
Public title
Study of Alirocumab (REGN727/SAR236553) added-on to Rosuvastatin Versus Other Lipid Modifying Treatments (LMT) (ODYSSEY OPTIONS II)
Scientific 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
Secondary ID [1] 0 0
R727-CL-1118
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Alirocumab
Treatment: Drugs - Rosuvastatin
Treatment: Drugs - Ezetimibe
Treatment: Drugs - Placebo

Active Comparator: Rosuvastatin 20 mg - Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received rosuvastatin 20 mg over-encapsulated tablet orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablet orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.

Active Comparator: Ezetimibe 10 mg + Rosuvastatin 10 mg - Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.

Experimental: Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg - Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels =70 mg/dL (1.81 mmol/L) or =100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.

Active Comparator: Rosuvastatin 40 mg - Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received rosuvastatin 40 mg over-encapsulated tablet orally QD, placebo for alirocumab Q2W SC injection, and placebo for ezetimibe QD over-encapsulated tablet orally added to stable LMT for 24 weeks.

Active Comparator: Ezetimibe 10 mg + Rosuvastatin 20 mg - Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for alirocumab Q2W SC injection added to stable LMT for 24 weeks.

Experimental: Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg - Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg Q2W SC injection, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels =70 mg/dL (1.81 mmol/L) or =100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.


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

Treatment: Drugs: Rosuvastatin
Rosuvastatin over-encapsulated tablets orally.

Treatment: Drugs: Ezetimibe
Ezetimibe over-encapsulated tablets orally.

Treatment: Drugs: Placebo
Placebo for alirocumab and ezetimibe.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
From Baseline to Week 24
Secondary outcome [1] 0 0
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).
Timepoint [1] 0 0
From Baseline to Week 24
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
From Baseline to Week 12
Secondary outcome [3] 0 0
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).
Timepoint [3] 0 0
From Baseline to Week 12
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
From Baseline to Week 24
Secondary outcome [5] 0 0
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).
Timepoint [5] 0 0
From Baseline to Week 24
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
From Baseline to Week 24
Secondary outcome [7] 0 0
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).
Timepoint [7] 0 0
From Baseline to Week 24
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
From Baseline to Week 24
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
From Baseline to Week 12
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
From Baseline to Week 12
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
From Baseline to Week 12
Secondary outcome [12] 0 0
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).
Timepoint [12] 0 0
Up to Week 24
Secondary outcome [13] 0 0
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).
Timepoint [13] 0 0
Up to Week 24
Secondary outcome [14] 0 0
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).
Timepoint [14] 0 0
Up to Week 24
Secondary outcome [15] 0 0
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).
Timepoint [15] 0 0
Up to Week 24
Secondary outcome [16] 0 0
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.
Timepoint [16] 0 0
From Baseline to Week 24
Secondary outcome [17] 0 0
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.
Timepoint [17] 0 0
From Baseline to Week 24
Secondary outcome [18] 0 0
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.
Timepoint [18] 0 0
From Baseline to Week 24
Secondary outcome [19] 0 0
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.
Timepoint [19] 0 0
From Baseline to Week 24
Secondary outcome [20] 0 0
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.
Timepoint [20] 0 0
From Baseline to Week 12
Secondary outcome [21] 0 0
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.
Timepoint [21] 0 0
From Baseline to Week 12
Secondary outcome [22] 0 0
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.
Timepoint [22] 0 0
From Baseline to Week 12
Secondary outcome [23] 0 0
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.
Timepoint [23] 0 0
From Baseline to Week 12

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Herston
Recruitment hospital [2] 0 0
- New Lambton Heights
Recruitment hospital [3] 0 0
- Perth
Recruitment hospital [4] 0 0
- Sherwood
Recruitment hospital [5] 0 0
- Woolloongabba
Recruitment postcode(s) [1] 0 0
- Herston
Recruitment postcode(s) [2] 0 0
- New Lambton Heights
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment postcode(s) [4] 0 0
- Sherwood
Recruitment postcode(s) [5] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maine
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Mississippi
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Montana
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oregon
Country [19] 0 0
United States of America
State/province [19] 0 0
Rhode Island
Country [20] 0 0
United States of America
State/province [20] 0 0
South Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Utah
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
France
State/province [26] 0 0
Dijon
Country [27] 0 0
France
State/province [27] 0 0
Lille
Country [28] 0 0
Germany
State/province [28] 0 0
Bad Oeynhausen
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Koeln
Country [31] 0 0
Germany
State/province [31] 0 0
Regensburg
Country [32] 0 0
Germany
State/province [32] 0 0
Ulm
Country [33] 0 0
Italy
State/province [33] 0 0
Chieti
Country [34] 0 0
Italy
State/province [34] 0 0
Genova
Country [35] 0 0
Italy
State/province [35] 0 0
Napoli
Country [36] 0 0
Italy
State/province [36] 0 0
Palermo
Country [37] 0 0
Italy
State/province [37] 0 0
Roma
Country [38] 0 0
Mexico
State/province [38] 0 0
Baja California
Country [39] 0 0
Mexico
State/province [39] 0 0
Distrito Federal
Country [40] 0 0
Mexico
State/province [40] 0 0
Guadalajara
Country [41] 0 0
Mexico
State/province [41] 0 0
Monterrey
Country [42] 0 0
Mexico
State/province [42] 0 0
Zapopan Jalisco
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
Santiago
Country [46] 0 0
Spain
State/province [46] 0 0
Sevilla
Country [47] 0 0
United Kingdom
State/province [47] 0 0
West Midlands
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Chester
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Peterborough
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Salford
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Stevenage

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Regeneron Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Sanofi
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT01730053
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications