Efficacy and Safety of Alirocumab Versus Placebo on Top of Maximally Tolerated Lipid Lowering Therapy in Patients With Hypercholesterolemia Who Have Type 1 or Type 2 Diabetes and Are Treated With Insulin (ODYSSEY DM - Insulin)

NCT02585778 | Completed Phase 3 Results

• 3 other identifiers: LPS143552015-000799-92U1111-1172-4772
• Study Type: interventional
• Target: 517
• Locations: 10 countries
• Sites: 110

Brief Summary

Primary Objectives:

• To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in participants with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy.
• To evaluate the safety and tolerability of alirocumab in participants with diabetes treated with insulin. Secondary Objective: To demonstrate that alirocumab was superior in comparison to placebo in its effects on other lipid parameters (i.e., measured LDL-C, non-high-density lipoprotein cholesterol \[non-HDL-C\], apolipoprotein B \[Apo B\], total cholesterol \[TC\], lipoprotein a \[Lp(a)\], high density lipoprotein cholesterol \[HDL-C\], triglyceride \[TG\] levels, triglyceride rich lipoproteins \[TGRL\], apolipoprotein A-1 \[Apo A-1\], apolipoprotein C-III \[Apo C-III\], and LDL particle number and size).

Conditions

Hypercholesterolaemia

Outcome Measures

Primary Outcomes (2)

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

  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

• Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)

  Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).

  From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)

Secondary Outcomes (26)

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

  From Baseline to Week 24

• Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis

  From Baseline to Week 24

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

  From Baseline to Week 24

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

  From Baseline to Week 24

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

  From Baseline to Week 24

Study Arms (2)

Alirocumab 75 mg Q2W/Up to 150 mg Q2W

EXPERIMENTAL

Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs 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) at Week 8.

Drug: Alirocumab; Drug: Lipid-Modifying Therapy (LMT); Drug: Antihyperglycemic Drug

Placebo Q2W

PLACEBO COMPARATOR

Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.

Drug: Placebo; Drug: Lipid-Modifying Therapy (LMT); Drug: Antihyperglycemic Drug

Interventions

Alirocumab DRUG

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Also known as: Praluent, SAR236553, REGN727

Alirocumab 75 mg Q2W/Up to 150 mg Q2W

Placebo DRUG

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Placebo Q2W

Lipid-Modifying Therapy (LMT) DRUG

Statins at stable, maximally tolerated dose with or without other LMT as clinically indicated.

Alirocumab 75 mg Q2W/Up to 150 mg Q2W; Placebo Q2W

Antihyperglycemic Drug DRUG

Insulin (injectable or inhaled) alone or with other antihyperglycemic drugs as clinically indicated.

Alirocumab 75 mg Q2W/Up to 150 mg Q2W; Placebo Q2W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants diagnosed with Type 1 or Type 2 diabetes at least one year prior to the screening visit (Week -3).
• Signed written informed consent
• Participants with type 1 or type 2 diabetes treated with insulin whose LDL-C levels were not adequately controlled with maximally tolerated lipid-modifying therapy
• LDL-C of 70 mg/dL or greater
• years of age or more
• Glycosylated hemoglobin (HbA1c) less than 10%
• History of cardiovascular disease (including coronary heart disease \[CHD\] and/or CHD risk equivalents) and/or at least one additional cardiovascular risk factor

You may not qualify if:

• Not on a stable dose of statin or other lipid modifying therapy for at least 4 weeks prior to screening or from screening to randomization, unless statin intolerant
• Triglycerides \>400 mg/dL
• Estimated glomerular filtration rate (eGFR) \<15 mL/min/1.73 m² according to the Modification of Diet in Renal Disease (MDRD) equation
• Currently received or planned to receive renal replacement therapy (for example, hemodialysis)
• Change in weight of more than 5 kilograms within the prior 2 months
• Not on a stable dose/regimen of insulin or other antidiabetic drugs for the past 3 months or planned to intensify insulin regimen during the study
• Not treated with insulin for at least 6 months
• Planned to start new lipid modifying therapy or change dose of current lipid modifying therapy during the study
• Body mass index (BMI) \>45 kg/m² or planned to undergo bariatric surgery, weight loss program, or initiate weight loss drugs during the study
• History of recent decompensation of diabetes within the prior 2 months (for example, diabetic ketoacidosis)
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (110)

Investigational Site Number 840020

Encino, California, 91436, United States

Location

Investigational Site Number 840002

Fresno, California, 93720, United States

Location

Investigational Site Number 840029

Oakland, California, 94612, United States

Location

Investigational Site Number 840027

Loveland, Colorado, 80538, United States

Location

Investigational Site Number 840026

Atlantis, Florida, 33462, United States

Location

Investigational Site Number 840006

Bradenton, Florida, 33180, United States

Location

Investigational Site Number 840023

Jacksonville, Florida, 32205, United States

Location

Investigational Site Number 840028

Palm Harbor, Florida, 34684, United States

Location

Investigational Site Number 840022

Ponte Vedra Beach, Florida, United States

Location

Investigational Site Number 840021

Roswell, Georgia, 30076, United States

Location

Investigational Site Number 840007

Springfield, Illinois, 62704, United States

Location

Investigational Site Number 840011

Indianapolis, Indiana, 46260, United States

Location

Investigational Site Number 840015

Valparaiso, Indiana, 46383, United States

Location

Investigational Site Number 840010

Des Moines, Iowa, 50314, United States

Location

Investigational Site Number 840005

Louisville, Kentucky, United States

Location

Investigational Site Number 840018

Auburn, Maine, 04210, United States

Location

Investigational Site Number 840013

Hyattsville, Maryland, 20782, United States

Location

Investigational Site Number 840016

Rockville, Maryland, 20852, United States

Location

Investigational Site Number 840004

Minneapolis, Minnesota, 55416, United States

Location

Investigational Site Number 840012

Jamaica, New York, 11432, United States

Location

Investigational Site Number 840014

Maumee, Ohio, 43537, United States

Location

Investigational Site Number 840009

Greer, South Carolina, 29651, United States

Location

Investigational Site Number 840024

Chattanooga, Tennessee, 37404, United States

Location

Investigational Site Number 840001

Austin, Texas, 78756, United States

Location

Investigational Site Number 840003

Dallas, Texas, 75230, United States

Location

Investigational Site Number 840019

Dallas, Texas, 75246, United States

Location

Investigational Site Number 840025

Houston, Texas, 77090, United States

Location

Investigational Site Number 840017

Ogden, Utah, 84405, United States

Location

Investigational Site Number 840008

Salt Lake City, Utah, 84102, United States

Location

Investigational Site Number 040002

Innsbruck, 6020, Austria

Location

Investigational Site Number 040005

Linz, 4021, Austria

Location

Investigational Site Number 040003

Salzburg, 5020, Austria

Location

Investigational Site Number 040004

Salzburg, 5026, Austria

Location

Investigational Site Number 040001

Vienna, 1160, Austria

Location

Investigational Site Number 056002

Edegem, 2650, Belgium

Location

Investigational Site Number 056003

Haine-Saint-Paul, 7100, Belgium

Location

Investigational Site Number 056001

Leuven, 3000, Belgium

Location

Investigational Site Number 250-008

Besançon, 25030, France

Location

Investigational Site Number 250-005

Corbeil-Essonnes, 91100, France

Location

Investigational Site Number 250-004

La Rochelle, 17019, France

Location

Investigational Site Number 250-003

Le Creusot, 71200, France

Location

Investigational Site Number 250-009

Mulhouse, France

Location

Investigational Site Number 250-002

Nantes, 44093, France

Location

Investigational Site Number 250-007

Paris, 75018, France

Location

Investigational Site Number 250-006

Strasbourg, 67098, France

Location

Investigational Site Number 250-001

Toulouse, 31059, France

Location

Investigational Site Number 276015

Aschaffenburg, 63739, Germany

Location

Investigational Site Number 276002

Berlin, 10115, Germany

Location

Investigational Site Number 276011

Dortmund, 44137, Germany

Location

Investigational Site Number 276019

Dresden, 01099, Germany

Location

Investigational Site Number 276014

Dresden, 01279, Germany

Location

Investigational Site Number 276009

Dresden, 01307, Germany

Location

Investigational Site Number 276021

Hamburg, 20246, Germany

Location

Investigational Site Number 276018

Hamburg, 22041, Germany

Location

Investigational Site Number 276005

Heidelberg, 69115, Germany

Location

Investigational Site Number 276013

Lüneburg, 21339, Germany

Location

Investigational Site Number 276022

Magdeburg, 39120, Germany

Location

Investigational Site Number 276008

Neumünster, 24534, Germany

Location

Investigational Site Number 276017

Neuwied, 56564, Germany

Location

Investigational Site Number 276004

Oldenburg, 26133, Germany

Location

Investigational Site Number 276003

Pirna, 01796, Germany

Location

Investigational Site Number 276006

Riesa, 01587, Germany

Location

Investigational Site Number 276010

Saarlouis, 66740, Germany

Location

Investigational Site Number 276016

Sulzbach-Rosenberg, 92237, Germany

Location

Investigational Site Number 380004

Catania, 95122, Italy

Location

Investigational Site Number 380003

Catanzaro, Italy

Location

Investigational Site Number 380011

Como, 22100, Italy

Location

Investigational Site Number 380006

Milan, 20132, Italy

Location

Investigational Site Number 380007

Milan, 20162, Italy

Location

Investigational Site Number 380005

Moncalieri, 10024, Italy

Location

Investigational Site Number 380009

Napoli, 80138, Italy

Location

Investigational Site Number 380008

Padua, Italy

Location

Investigational Site Number 380002

Palermo, 90127, Italy

Location

Investigational Site Number 380001

Pisa, 56124, Italy

Location

Investigational Site Number 380010

Roma, 00133, Italy

Location

Investigational Site Number 380012

Verona, 37126, Italy

Location

Investigational Site Number 528002

Apeldoorn, 7334 DZ, Netherlands

Location

Investigational Site Number 528005

Groningen, Netherlands

Location

Investigational Site Number 528003

Hoogeveen, 7909AA, Netherlands

Location

Investigational Site Number 528001

Rotterdam, 3045PM, Netherlands

Location

Investigational Site Number 528004

Utrecht, Netherlands

Location

Investigational Site Number 724007

Badalona, 08915, Spain

Location

Investigational Site Number 724001

Barcelona, 08025, Spain

Location

Investigational Site Number 724006

Ferrol, 15405, Spain

Location

Investigational Site Number 724013

Granada, 18003, Spain

Location

Investigational Site Number 724005

Madrid, 28040, Spain

Location

Investigational Site Number 724004

Madrid, Spain

Location

Investigational Site Number 724011

Majadahonda, 28222, Spain

Location

Investigational Site Number 724008

Málaga, 29010, Spain

Location

Investigational Site Number 724014

Oviedo, 33006, Spain

Location

Investigational Site Number 724009

Palma de Mallorca, 07198, Spain

Location

Investigational Site Number 724002

Pamplona, 31008, Spain

Location

Investigational Site Number 724010

Sant Joan Despí, 08970, Spain

Location

Investigational Site Number 724012

Segovia, Spain

Location

Investigational Site Number 724003

Seville, 41071, Spain

Location

Investigational Site Number 756001

Olten, 4600, Switzerland

Location

Investigational Site Number 756003

Sankt Gallen, 9016, Switzerland

Location

Investigational Site Number 826010

Airdrie, ML60JS, United Kingdom

Location

Investigational Site Number 826011

Bath, BA13NG, United Kingdom

Location

Investigational Site Number 826009

Bournemouth, BH77DW, United Kingdom

Location

Investigational Site Number 826005

Bradford, BD96RJ, United Kingdom

Location

Investigational Site Number 826004

Bristol, BS28HW, United Kingdom

Location

Investigational Site Number 826001

Burton-on-Trent, DE13 0RB, United Kingdom

Location

Investigational Site Number 826015

Durham, DH15TW, United Kingdom

Location

Investigational Site Number 826012

High Wycombe, HP112TT, United Kingdom

Location

Investigational Site Number 826007

Manchester, M239LT, United Kingdom

Location

Investigational Site Number 826006

Peterborough, PE39QZ, United Kingdom

Location

Investigational Site Number 826003

Southampton, SO303JB, United Kingdom

Location

Investigational Site Number 826008

Truro, TR13LJ, United Kingdom

Location

Investigational Site Number 826002

Welwyn Garden City, AL74HQ, United Kingdom

Location

Related Publications (3)

• Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.

  PMID: 33078867 DERIVED

• Ray KK, Del Prato S, Muller-Wieland D, Cariou B, Colhoun HM, Tinahones FJ, Domenger C, Letierce A, Mandel J, Samuel R, Bujas-Bobanovic M, Leiter LA. Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies. Cardiovasc Diabetol. 2019 Nov 9;18(1):149. doi: 10.1186/s12933-019-0951-9.

  PMID: 31706300 DERIVED

• Leiter LA, Cariou B, Muller-Wieland D, Colhoun HM, Del Prato S, Tinahones FJ, Ray KK, Bujas-Bobanovic M, Domenger C, Mandel J, Samuel R, Henry RR. Efficacy and safety of alirocumab in insulin-treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM-INSULIN randomized trial. Diabetes Obes Metab. 2017 Dec;19(12):1781-1792. doi: 10.1111/dom.13114. Epub 2017 Oct 10.

  PMID: 28905478 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab; Hypoglycemic Agents

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2015
• First Posted: October 23, 2015
• Study Start: October 23, 2015
• Primary Completion: April 3, 2017
• Study Completion: April 3, 2017
• Last Updated: May 17, 2018
• Results First Posted: May 17, 2018

Record last verified: 2018-04

Locations

FR (9); ES (14); AU (5); DE (18); NL (5); GB (13); US (29); CH (2); IT (12); BE (3)