Clinical trial NCT01730040: Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2012-11-21
Enrollment: 355
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

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).

Primary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: 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
timeFrame: Up to Week 24
measure: 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
timeFrame: Up to Week 24
measure: Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
timeFrame: Up to Week 24
measure: Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Anaheim
country: United States
state: California
city: Beverly Hills
country: United States
state: California
city: Lakeland
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Northridge
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Milford
country: United States
state: Connecticut
city: Atlantis
country: United States
state: Florida
city: Boca Raton
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami (2 locations)
country: United States
state: Florida
city: Oviedo
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Boise
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Morton
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Newton
country: United States
state: Kansas
city: Overland Park
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Auburn
country: United States
state: Maine
city: Bethesda
country: United States
state: Maryland
city: Edina
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Olive Branch
country: United States
state: Mississippi
city: Port Gibson
country: United States
state: Mississippi
city: St. Louis
country: United States
state: Missouri
city: Butte
country: United States
state: Montana
city: Las Vegas
country: United States
state: Nevada
city: Williamsville
country: United States
state: New York
city: Winston-Salem
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Warwick
country: United States
state: Rhode Island
city: Greer
country: United States
state: South Carolina
city: Summerville
country: United States
state: South Carolina
city: Kingsport
country: United States
state: Tennessee
city: Dallas (2 locations)
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Marion
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Renton
country: United States
state: Washington
city: Herston QLD
country: Australia
city: New Lambton Heights
country: Australia
city: Perth
country: Australia
city: Sherwood
country: Australia
city: Woolloongabba
country: Australia
city: Brampton
country: Canada
state: Ontario
city: Etobicoke
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Newmarke
country: Canada
state: Ontario
city: Thornhill
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Chicoutimi
country: Canada
state: Quebec
city: Dijon
country: France
city: Lille
country: France
city: Venissieux
country: France
city: Bad Oeynhausen
country: Germany
city: Berlin
country: Germany
city: Koeln
country: Germany
city: Munich
country: Germany
city: Regensburg
country: Germany
city: Ulm
country: Germany
city: Chiete
country: Italy
city: Genova
country: Italy
city: Napoli
country: Italy
city: Palermo
country: Italy
city: Roma (2 locations)
country: Italy
city: Distrito Federal
country: Mexico
city: Guadalajara, Jalisco
country: Mexico
city: Guadalajara
country: Mexico
city: Monterrey Nuevo Leon
country: Mexico
city: Tijuana Baja California
country: Mexico
city: Zapopan Jalisco
country: Mexico
city: Barcelona (3 locations)
country: Spain
city: Madrid
country: Spain
city: Sant Joan Despi
country: Spain
city: Carmarthen
country: United Kingdom
city: Chester
country: United Kingdom
city: Peterborough
country: United Kingdom
city: Salford
country: United Kingdom
city: Stevenage
country: United Kingdom
city: West Bromwich, West Midlands
country: United Kingdom
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.