Efficacy and Safety of Alirocumab Versus Usual Care on Top of Maximally Tolerated Statin Therapy in Patients With Type 2 Diabetes and Mixed Dyslipidemia (ODYSSEY DM-Dyslipidemia)

NCT02642159 | Completed Phase 4 Results

• 3 other identifiers: LPS143542015-001934-19U1111-1172-5262
• Study Type: interventional
• Target: 413
• Locations: 15 countries
• Sites: 119

Brief Summary

Primary Objective: To demonstrate the superiority of alirocumab in comparison with usual care in the reduction of non-high-density lipoprotein cholesterol (non-HDL-C) in participants with type 2 diabetes and mixed dyslipidemia at high cardiovascular risk with non-HDL-C not adequately controlled with maximally tolerated statin therapy. Secondary Objectives:

• To demonstrate whether alirocumab is superior in comparison with usual care in its effects on other lipid parameters (ie, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), total cholesterol (Total -C), lipoprotein a (Lp\[a\]), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), triglyceride rich lipoproteins (TGRLs), apolipoprotein A-1 (Apo A-1), apolipoprotein C-III (Apo C-III), lipid subfractions by nuclear magnetic resonance (NMR) spectroscopy (ie, LDL-C particle size and LDL, very low-density lipoprotein \[VLDL\], HDL, and intermediate-density lipoprotein \[IDL\] particle number).
• To assess changes in glycemic parameters with alirocumab vs. usual care treatment.
• To demonstrate the safety and tolerability of alirocumab.
• To evaluate treatment acceptance of alirocumab.
• To evaluate proprotein convertase subtilisin kexin type 9 (PCSK9) concentrations and antibody development.
• To demonstrate the superiority of alirocumab vs. fenofibrate on non-HDL-C and other lipid parameters (subgroup analysis).

Conditions

Dyslipidemia

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Non-HDL-C at Week 24: Overall 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 8 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

  From Baseline to Week 24

• Percent Change From Baseline in Non-HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum

  Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

  From Baseline to Week 24

Secondary Outcomes (21)

• Percent Change From Baseline in Measured Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24: Overall ITT Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Measured LDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum

  From Baseline to Week 24

• Percent Change From Baseline in Non-HDL-C at Week 12: Overall ITT Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Non-HDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum

  From Baseline to Week 24

• Percent Change From Baseline in Measured LDL-C at Week 12: Overall 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 insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other lipid modifying therapy (LMT) for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-high-density lipoprotein cholesterol (non-HDL-C) levels \>=100 mg/dL (2.59 mmol/L) at Week 8.

Drug: Alirocumab; Drug: Statins; Drug: Antihyperglycemic Drug

Usual Care

ACTIVE COMPARATOR

Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.

Drug: Statins; Drug: Ezetimibe; Drug: Fenofibrate; Drug: Nicotinic acid; Drug: Omega-3 fatty acids; 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: SAR236553, REGN727, Praluent

Alirocumab 75 mg Q2W/Up to 150 mg Q2W

Statins DRUG

Statins at stable dose without other LMT as clinically indicated.

Alirocumab 75 mg Q2W/Up to 150 mg Q2W; Usual Care

Ezetimibe DRUG

Pharmaceutical form: tablet Route of administration: oral

Usual Care

Fenofibrate DRUG

Pharmaceutical form: tablet Route of administration: oral

Usual Care

Nicotinic acid DRUG

Pharmaceutical form: tablet Route of administration: oral

Usual Care

Omega-3 fatty acids DRUG

Pharmaceutical form: tablet Route of administration: oral

Usual Care

Antihyperglycemic Drug DRUG

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

Alirocumab 75 mg Q2W/Up to 150 mg Q2W; Usual Care

Eligibility Criteria

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

You may qualify if:

• Participants with type 2 diabetes and mixed dyslipidemia whose non-HDL-C was not adequately controlled with a stable, maximum dose/regimen of statin that was tolerated by the participant.
• years of age or more.
• Documented history of atherosclerotic cardiovascular disease (ASCVD) or at least one additional cardiovascular risk factor.
• Non-HDL-C of 100 mg/dL or greater.
• Triglycerides greater than or equal to 150 mg/dL and less than 500 mg/dL.
• Stable anti-hyperglycemic agents for at least 3 months prior to the screening visit and between screening and randomization (including stable insulin dose defined as no variation more than 30% in daily insulin dose within the preceding 3 months, as judged by the Investigator).
• No change in weight of more than 5 kg within the prior 3 months.
• On stable dose of medications that are known to influence weight and/or lipids within the last 3 months.

You may not qualify if:

• Use of any lipid modifying therapies other than statins within the last 4 weeks (eg, ezetimibe, fenofibrate, nicotinic acid, omega-3 fatty acids, etc.) or use of over the counter products/nutraceuticals known to impact lipids (eg, red yeast rice) within the last 4 weeks.
• Currently drinking more than 2 standard alcoholic drinks per day.
• Body Mass Index (BMI) \>45 kg/m² or currently enrolled in a weight loss program and still in active phase of weight loss.
• Glycosylated hemoglobin (HbA1c) 9% or greater.
• 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 (119)

Investigational Site Number 840-163

Little Rock, Arkansas, 72205, United States

Location

Investigational Site Number 840-141

Fresno, California, 93720, United States

Location

Investigational Site Number 840-152

Huntington Beach, California, 92648, United States

Location

Investigational Site Number 840-115

La Jolla, California, 92037, United States

Location

Investigational Site Number 840-118

Los Angeles, California, 90057, United States

Location

Investigational Site Number 840-106

Northridge, California, 91325, United States

Location

Investigational Site Number 840-176

Port Hueneme, California, 93041, United States

Location

Investigational Site Number 840-122

Tarzana, California, 91356, United States

Location

Investigational Site Number 840-156

Tustin, California, 92780-6953, United States

Location

Investigational Site Number 840-160

Van Nuys, California, 91405, United States

Location

Investigational Site Number 840-107

Boca Raton, Florida, 33434, United States

Location

Investigational Site Number 840-170

Boynton Beach, Florida, 33472, United States

Location

Investigational Site Number 840-114

Bradenton, Florida, 34201, United States

Location

Investigational Site Number 840-132

Ocoee, Florida, 34761, United States

Location

Investigational Site Number 840-179

Oviedo, Florida, 32765, United States

Location

Investigational Site Number 840-123

Tampa, Florida, 33634, United States

Location

Investigational Site Number 840-137

Bainbridge, Georgia, 39819, United States

Location

Investigational Site Number 840-128

Columbus, Georgia, 31904, United States

Location

Investigational Site Number 840-169

Stockbridge, Georgia, 30281, United States

Location

Investigational Site Number 840-167

Idaho Falls, Idaho, 83404, United States

Location

Investigational Site Number 840-161

Chicago, Illinois, 60607, United States

Location

Investigational Site Number 840-184

Crystal Lake, Illinois, 60012, United States

Location

Investigational Site Number 840-174

Evanston, Illinois, 60201, United States

Location

Investigational Site Number 840-138

Springfield, Illinois, 62711, United States

Location

Investigational Site Number 840-108

Louisville, Kentucky, United States

Location

Investigational Site Number 840-183

Paducah, Kentucky, 42003, United States

Location

Investigational Site Number 840-190

Metairie, Louisiana, 70006, United States

Location

Investigational Site Number 840-151

Rockville, Maryland, 20852, United States

Location

Investigational Site Number 840-113

Jefferson City, Missouri, 65109, United States

Location

Investigational Site Number 840-120

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840-148

Omaha, Nebraska, 68131-2137, United States

Location

Investigational Site Number 840-101

Las Vegas, Nevada, 89119, United States

Location

Investigational Site Number 840-140

Las Vegas, Nevada, 89128, United States

Location

Investigational Site Number 840-178

Albany, New York, 12206, United States

Location

Investigational Site Number 840-181

New York, New York, 10016, United States

Location

Investigational Site Number 840-157

New York, New York, 10029, United States

Location

Investigational Site Number 840-188

Greensboro, North Carolina, 27408, United States

Location

Investigational Site Number 840-131

Morehead City, North Carolina, 28557, United States

Location

Investigational Site Number 840-158

Morganton, North Carolina, 28655, United States

Location

Investigational Site Number 840-129

Fargo, North Dakota, 58103, United States

Location

Investigational Site Number 840-104

Columbus, Ohio, 43213, United States

Location

Investigational Site Number 840-105

Marion, Ohio, 43302, United States

Location

Investigational Site Number 840-175

Maumee, Ohio, 43537, United States

Location

Investigational Site Number 840-136

Bend, Oregon, 97702, United States

Location

Investigational Site Number 840-187

Murrells Inlet, South Carolina, 29576-9351, United States

Location

Investigational Site Number 840-111

Summerville, South Carolina, 29485, United States

Location

Investigational Site Number 840-147

Chattanooga, Tennessee, 37404, United States

Location

Investigational Site Number 840-159

Knoxville, Tennessee, 37920, United States

Location

Investigational Site Number 840-153

Dallas, Texas, 75230, United States

Location

Investigational Site Number 840-143

Houston, Texas, 77095, United States

Location

Investigational Site Number 840-168

Houston, Texas, 77099, United States

Location

Investigational Site Number 840-142

Round Rock, Texas, 78681, United States

Location

Investigational Site Number 840-133

Tomball, Texas, 77375, United States

Location

Investigational Site Number 840-185

Orem, Utah, 84058, United States

Location

Investigational Site Number 840-150

Salt Lake City, Utah, 84102, United States

Location

Investigational Site Number 840-126

Chesapeake, Virginia, 23321, United States

Location

Investigational Site Number 840-171

Richmond, Virginia, 23249, United States

Location

Investigational Site Number 036102

Herston, 4006, Australia

Location

Investigational Site Number 036104

Merewether, 2291, Australia

Location

Investigational Site Number 036101

St Leonards, 2065, Australia

Location

Investigational Site Number 076103

Campinas, 13060080, Brazil

Location

Investigational Site Number 076104

Fortaleza, 60115-282, Brazil

Location

Investigational Site Number 076105

São Paulo, 01223-001, Brazil

Location

Investigational Site Number 076101

São Paulo, 04040-001, Brazil

Location

Investigational Site Number 076106

São Paulo, 05403-900, Brazil

Location

Investigational Site Number 076102

São Paulo, Brazil

Location

Investigational Site Number 246102

Oulu, 90100, Finland

Location

Investigational Site Number 246101

Oulu, 90220, Finland

Location

Investigational Site Number 246104

Tampere, 33520, Finland

Location

Investigational Site Number 276112

Berlin, 13347, Germany

Location

Investigational Site Number 276109

Berlin, 13353, Germany

Location

Investigational Site Number 276104

Dippoldiswalde, 01744, Germany

Location

Investigational Site Number 276101

Dresden, 01307, Germany

Location

Investigational Site Number 276110

Essen, 45355, Germany

Location

Investigational Site Number 276108

Essen, 45359, Germany

Location

Investigational Site Number 276111

Goch, 47574, Germany

Location

Investigational Site Number 276107

Karlsruhe, 76199, Germany

Location

Investigational Site Number 276103

Künzing, 94550, Germany

Location

Investigational Site Number 276102

Oldenburg in Holstein, 23758, Germany

Location

Investigational Site Number 376101

Beersheba, Israel

Location

Investigational Site Number 376103

Petah Tikva, Israel

Location

Investigational Site Number 376104

Petah Tikva, Israel

Location

Investigational Site Number 376102

Rehovot, Israel

Location

Investigational Site Number 376106

Tel Aviv, Israel

Location

Investigational Site Number 380104

Bergamo, 24127, Italy

Location

Investigational Site Number 380107

Catanzaro, 88100, Italy

Location

Investigational Site Number 380103

Napoli, 80131, Italy

Location

Investigational Site Number 380108

Padua, 35100, Italy

Location

Investigational Site Number 380106

Partinico, 90047, Italy

Location

Investigational Site Number 380101

Pisa, 56124, Italy

Location

Investigational Site Number 380105

Roma, 00168, Italy

Location

Investigational Site Number 380102

Torino, 10126, Italy

Location

Investigational Site Number 414101

Kuwait City, Kuwait

Location

Investigational Site Number 422101

Beirut, Lebanon

Location

Investigational Site Number 422102

Hazmiyeh, Lebanon

Location

Investigational Site Number 578101

Oslo, 0372, Norway

Location

Investigational Site Number 578102

Oslo, 0407, Norway

Location

Investigational Site Number 752102

Gothenburg, 41345, Sweden

Location

Investigational Site Number 752101

Stockholm, 14186, Sweden

Location

Investigational Site Number 756101

Geneva, 1205, Switzerland

Location

Investigational Site Number 756102

Olten, 4600, Switzerland

Location

Investigational Site Number 756103

Reinach, 4153, Switzerland

Location

Investigational Site Number 792105

Adana, 01250, Turkey (Türkiye)

Location

Investigational Site Number 792106

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number 792102

Ankara, Turkey (Türkiye)

Location

Investigational Site Number 792108

Çorum, Turkey (Türkiye)

Location

Investigational Site Number 792109

Hatay, 31030, Turkey (Türkiye)

Location

Investigational Site Number 792104

Izmir, 35340, Turkey (Türkiye)

Location

Investigational Site Number 792101

Izmir, Turkey (Türkiye)

Location

Investigational Site Number 792110

Izmir, Turkey (Türkiye)

Location

Investigational Site Number 792107

Kayseri, 38039, Turkey (Türkiye)

Location

Investigational Site Number 792103

Samsun, Turkey (Türkiye)

Location

Investigational Site Number 784101

Dubai, 4545, United Arab Emirates

Location

Investigational Site Number 826104

Exeter, EX25DW, United Kingdom

Location

Investigational Site Number 826106

Manchester, m139wl, United Kingdom

Location

Investigational Site Number 826105

Middlesbrough, TS4 3BW, United Kingdom

Location

Investigational Site Number 826103

Stevenage, SG14AB, United Kingdom

Location

Investigational Site Number 826101

Torquay, TQ27AA, United Kingdom

Location

Investigational Site Number 826102

West Bromwich, B714HJ, United Kingdom

Location

Related Publications (5)

• 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

• Colhoun HM, Leiter LA, Muller-Wieland D, Cariou B, Ray KK, Tinahones FJ, Domenger C, Letierce A, Israel M, Samuel R, Del Prato S. Effect of alirocumab on individuals with type 2 diabetes, high triglycerides, and low high-density lipoprotein cholesterol. Cardiovasc Diabetol. 2020 Feb 8;19(1):14. doi: 10.1186/s12933-020-0991-1.

  PMID: 32035487 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

• Ray KK, Leiter LA, Muller-Wieland D, Cariou B, Colhoun HM, Henry RR, Tinahones FJ, Bujas-Bobanovic M, Domenger C, Letierce A, Samuel R, Del Prato S. Alirocumab vs usual lipid-lowering care as add-on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM-DYSLIPIDEMIA randomized trial. Diabetes Obes Metab. 2018 Jun;20(6):1479-1489. doi: 10.1111/dom.13257. Epub 2018 Mar 23.

  PMID: 29436756 DERIVED

• Muller-Wieland D, Leiter LA, Cariou B, Letierce A, Colhoun HM, Del Prato S, Henry RR, Tinahones FJ, Aurand L, Maroni J, Ray KK, Bujas-Bobanovic M. Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk. Cardiovasc Diabetol. 2017 May 25;16(1):70. doi: 10.1186/s12933-017-0552-4.

  PMID: 28545518 DERIVED

MeSH Terms

Conditions

Dyslipidemias

Interventions

alirocumab; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ezetimibe; Fenofibrate; Niacin; Fatty Acids, Omega-3; Hypoglycemic Agents

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils; Physiological Effects of Drugs

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 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2015
• First Posted: December 30, 2015
• Study Start: March 15, 2016
• Primary Completion: March 22, 2017
• Study Completion: May 15, 2017
• Last Updated: May 1, 2018
• Results First Posted: May 1, 2018

Record last verified: 2018-03

Locations

NO (2); TU (10); FI (3); US (57); DE (10); AU (3); BR (6); AE (1); IL (5); SE (2); LE (2); IT (8); KU (1); CH (3); GB (6)