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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01730040




Registration number
NCT01730040
Ethics application status
Date submitted
9/11/2012
Date registered
21/11/2012
Date last updated
31/08/2015

Titles & IDs
Public title
Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I)
Scientific title
A Randomized, Double-Blind Study of the Efficacy and Safety of Alirocumab 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 Atorvastatin
Secondary ID [1] 0 0
R727-CL-1110
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 - Atorvastatin
Treatment: Drugs - Ezetimibe
Treatment: Drugs - Rosuvastatin
Treatment: Drugs - Placebo

Active comparator: Atorvastatin 40 mg - Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.

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

Experimental: Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg - Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets 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: Atorvastatin 80 mg - Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.

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

Active comparator: Ezetimibe 10 mg + Atorvastatin 40 mg - Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.

Experimental: Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg - Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets 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: Atorvastatin
Atorvastatin over-encapsulated tablets orally.

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

Treatment: Drugs: Rosuvastatin
Rosuvastatin 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
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
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
Timepoint [2] 0 0
From Baseline to Week 24
Secondary outcome [3] 0 0
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Timepoint [3] 0 0
From Baseline to Week 24
Secondary outcome [4] 0 0
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
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
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
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
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
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
Timepoint [9] 0 0
From Baseline to Week 24
Secondary outcome [10] 0 0
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Timepoint [10] 0 0
From Baseline to Week 24
Secondary outcome [11] 0 0
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Timepoint [11] 0 0
From Baseline to Week 24
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
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
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
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
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
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
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
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
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
Timepoint [20] 0 0
From Baseline to Week 24
Secondary outcome [21] 0 0
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Timepoint [21] 0 0
From Baseline to Week 24
Secondary outcome [22] 0 0
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Timepoint [22] 0 0
From Baseline to Week 24
Secondary outcome [23] 0 0
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Timepoint [23] 0 0
From Baseline to Week 24

Eligibility
Key inclusion criteria
1. Patients with screening (visit 1) LDL-C greater than or equal to 70 mg/dL with documented CVD, not adequately controlled with a daily dose of atorvastatin. OR
2. Patients with screening (visit 1) LDL-C greater than or equal to 100 mg/dL at high risk for CVD who are not adequately controlled with a daily dose of atorvastatin.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. LDL-C greater than 250 mg/dL
2. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented CVD
3. LDL-C less than 100 mg/dL at the screening visit in patients without history of documented CHD or non-CHD CVD, but with other risk factors
4. TG greater than 400 mg/dL
5. Homozygous FH (clinically or previous genotyping)
6. Currently taking a statin that is not atorvastatin
7. Currently taking Ezetimibe (EZE)
8. Not on a stable dose of allowable lipid modifying treatments (LMT)

(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
1/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2014
Sample size
Target
Accrual to date
Final
355
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Herston QLD
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 QLD
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
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Maine
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Mississippi
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
Montana
Country [17] 0 0
United States of America
State/province [17] 0 0
Nevada
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Oklahoma
Country [22] 0 0
United States of America
State/province [22] 0 0
Rhode Island
Country [23] 0 0
United States of America
State/province [23] 0 0
South Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Tennessee
Country [25] 0 0
United States of America
State/province [25] 0 0
Texas
Country [26] 0 0
United States of America
State/province [26] 0 0
Utah
Country [27] 0 0
United States of America
State/province [27] 0 0
Washington
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
France
State/province [30] 0 0
Dijon
Country [31] 0 0
France
State/province [31] 0 0
Lille
Country [32] 0 0
France
State/province [32] 0 0
Venissieux
Country [33] 0 0
Germany
State/province [33] 0 0
Bad Oeynhausen
Country [34] 0 0
Germany
State/province [34] 0 0
Berlin
Country [35] 0 0
Germany
State/province [35] 0 0
Koeln
Country [36] 0 0
Germany
State/province [36] 0 0
Munich
Country [37] 0 0
Germany
State/province [37] 0 0
Regensburg
Country [38] 0 0
Germany
State/province [38] 0 0
Ulm
Country [39] 0 0
Italy
State/province [39] 0 0
Chiete
Country [40] 0 0
Italy
State/province [40] 0 0
Genova
Country [41] 0 0
Italy
State/province [41] 0 0
Napoli
Country [42] 0 0
Italy
State/province [42] 0 0
Palermo
Country [43] 0 0
Italy
State/province [43] 0 0
Roma (2 locations)
Country [44] 0 0
Mexico
State/province [44] 0 0
Distrito Federal
Country [45] 0 0
Mexico
State/province [45] 0 0
Guadalajara, Jalisco
Country [46] 0 0
Mexico
State/province [46] 0 0
Guadalajara
Country [47] 0 0
Mexico
State/province [47] 0 0
Monterrey Nuevo Leon
Country [48] 0 0
Mexico
State/province [48] 0 0
Tijuana Baja California
Country [49] 0 0
Mexico
State/province [49] 0 0
Zapopan Jalisco
Country [50] 0 0
Spain
State/province [50] 0 0
Barcelona (3 locations)
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Spain
State/province [52] 0 0
Sant Joan Despi
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Carmarthen
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Chester
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Peterborough
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Salford
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Stevenage
Country [58] 0 0
United Kingdom
State/province [58] 0 0
West Bromwich, West Midlands

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
This is a randomized, double-blind, active-comparator, parallel-group study in patients at high cardiovascular risk with nonfamilial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH).
Trial website
https://clinicaltrials.gov/study/NCT01730040
Trial related presentations / publications
Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.
Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.116.024604. Epub 2016 Oct 24.
Bays H, Gaudet D, Weiss R, Ruiz JL, Watts GF, Gouni-Berthold I, Robinson J, Zhao J, Hanotin C, Donahue S. Alirocumab as Add-On to Atorvastatin Versus Other Lipid Treatment Strategies: ODYSSEY OPTIONS I Randomized Trial. J Clin Endocrinol Metab. 2015 Aug;100(8):3140-8. doi: 10.1210/jc.2015-1520. Epub 2015 Jun 1.
Robinson JG, Colhoun HM, Bays HE, Jones PH, Du Y, Hanotin C, Donahue S. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014 Oct;37(10):597-604. doi: 10.1002/clc.22327. Epub 2014 Sep 30.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01730040