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)

NCT ID: NCT02642159

Last Updated: 2018-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 413 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-15
• Study Completion Date: 2017-05-15

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).

Detailed Description

The maximum study duration was approximately 9 months per participant, including a 6 month treatment period, a screening period of up to 3 weeks, and an 8 week safety observation period.

For the purpose of scientific communication, a first-step analysis (both efficacy and safety) was performed at the Week 24 cut-off date. A second-step analysis was performed once all participants had completed the study to include a final update of the safety analysis.

Conditions

Dyslipidemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Alirocumab 75 mg Q2W/Up to 150 mg Q2W

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.

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

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

Statins

Intervention Type: DRUG

Statins at stable dose without other LMT as clinically indicated.

Antihyperglycemic Drug

Intervention Type: DRUG

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

Usual Care

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.

Group Type: ACTIVE_COMPARATOR

Statins

Intervention Type: DRUG

Statins at stable dose without other LMT as clinically indicated.

Ezetimibe

Intervention Type: DRUG

Pharmaceutical form: tablet Route of administration: oral

Fenofibrate

Intervention Type: DRUG

Pharmaceutical form: tablet Route of administration: oral

Nicotinic acid

Intervention Type: DRUG

Pharmaceutical form: tablet Route of administration: oral

Omega-3 fatty acids

Intervention Type: DRUG

Pharmaceutical form: tablet Route of administration: oral

Antihyperglycemic Drug

Intervention Type: DRUG

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

Interventions

Alirocumab

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

Intervention Type: DRUG

Statins

Statins at stable dose without other LMT as clinically indicated.

Intervention Type: DRUG

Ezetimibe

Pharmaceutical form: tablet Route of administration: oral

Intervention Type: DRUG

Fenofibrate

Pharmaceutical form: tablet Route of administration: oral

Intervention Type: DRUG

Nicotinic acid

Pharmaceutical form: tablet Route of administration: oral

Intervention Type: DRUG

Omega-3 fatty acids

Pharmaceutical form: tablet Route of administration: oral

Intervention Type: DRUG

Antihyperglycemic Drug

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

Intervention Type: DRUG

Other Intervention Names

SAR236553; REGN727; Praluent

Eligibility Criteria

Inclusion Criteria

• 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.
• 18 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840-163

Little Rock, Arkansas, United States

Investigational Site Number 840-141

Fresno, California, United States

Investigational Site Number 840-152

Huntington Beach, California, United States

Investigational Site Number 840-115

La Jolla, California, United States

Investigational Site Number 840-118

Los Angeles, California, United States

Investigational Site Number 840-106

Northridge, California, United States

Investigational Site Number 840-176

Port Hueneme, California, United States

Investigational Site Number 840-122

Tarzana, California, United States

Investigational Site Number 840-156

Tustin, California, United States

Investigational Site Number 840-160

Van Nuys, California, United States

Investigational Site Number 840-107

Boca Raton, Florida, United States

Investigational Site Number 840-170

Boynton Beach, Florida, United States

Investigational Site Number 840-114

Bradenton, Florida, United States

Investigational Site Number 840-132

Ocoee, Florida, United States

Investigational Site Number 840-179

Oviedo, Florida, United States

Investigational Site Number 840-123

Tampa, Florida, United States

Investigational Site Number 840-137

Bainbridge, Georgia, United States

Investigational Site Number 840-128

Columbus, Georgia, United States

Investigational Site Number 840-169

Stockbridge, Georgia, United States

Investigational Site Number 840-167

Idaho Falls, Idaho, United States

Investigational Site Number 840-161

Chicago, Illinois, United States

Investigational Site Number 840-184

Crystal Lake, Illinois, United States

Investigational Site Number 840-174

Evanston, Illinois, United States

Investigational Site Number 840-138

Springfield, Illinois, United States

Investigational Site Number 840-108

Louisville, Kentucky, United States

Investigational Site Number 840-183

Paducah, Kentucky, United States

Investigational Site Number 840-190

Metairie, Louisiana, United States

Investigational Site Number 840-151

Rockville, Maryland, United States

Investigational Site Number 840-113

Jefferson City, Missouri, United States

Investigational Site Number 840-120

St Louis, Missouri, United States

Investigational Site Number 840-148

Omaha, Nebraska, United States

Investigational Site Number 840-101

Las Vegas, Nevada, United States

Investigational Site Number 840-140

Las Vegas, Nevada, United States

Investigational Site Number 840-178

Albany, New York, United States

Investigational Site Number 840-181

New York, New York, United States

Investigational Site Number 840-157

New York, New York, United States

Investigational Site Number 840-188

Greensboro, North Carolina, United States

Investigational Site Number 840-131

Morehead City, North Carolina, United States

Investigational Site Number 840-158

Morganton, North Carolina, United States

Investigational Site Number 840-129

Fargo, North Dakota, United States

Investigational Site Number 840-104

Columbus, Ohio, United States

Investigational Site Number 840-105

Marion, Ohio, United States

Investigational Site Number 840-175

Maumee, Ohio, United States

Investigational Site Number 840-136

Bend, Oregon, United States

Investigational Site Number 840-187

Murrells Inlet, South Carolina, United States

Investigational Site Number 840-111

Summerville, South Carolina, United States

Investigational Site Number 840-147

Chattanooga, Tennessee, United States

Investigational Site Number 840-159

Knoxville, Tennessee, United States

Investigational Site Number 840-153

Dallas, Texas, United States

Investigational Site Number 840-143

Houston, Texas, United States

Investigational Site Number 840-168

Houston, Texas, United States

Investigational Site Number 840-142

Round Rock, Texas, United States

Investigational Site Number 840-133

Tomball, Texas, United States

Investigational Site Number 840-185

Orem, Utah, United States

Investigational Site Number 840-150

Salt Lake City, Utah, United States

Investigational Site Number 840-126

Chesapeake, Virginia, United States

Investigational Site Number 840-171

Richmond, Virginia, United States

Investigational Site Number 036102

Herston, , Australia

Investigational Site Number 036104

Merewether, , Australia

Investigational Site Number 036101

St Leonards, , Australia

Investigational Site Number 076103

Campinas, , Brazil

Investigational Site Number 076104

Fortaleza, , Brazil

Investigational Site Number 076105

São Paulo, , Brazil

Investigational Site Number 076101

São Paulo, , Brazil

Investigational Site Number 076106

São Paulo, , Brazil

Investigational Site Number 076102

São Paulo, , Brazil

Investigational Site Number 246102

Oulu, , Finland

Investigational Site Number 246101

Oulu, , Finland

Investigational Site Number 246104

Tampere, , Finland

Investigational Site Number 276112

Berlin, , Germany

Investigational Site Number 276109

Berlin, , Germany

Investigational Site Number 276104

Dippoldiswalde, , Germany

Investigational Site Number 276101

Dresden, , Germany

Investigational Site Number 276110

Essen, , Germany

Investigational Site Number 276108

Essen, , Germany

Investigational Site Number 276111

Goch, , Germany

Investigational Site Number 276107

Karlsruhe, , Germany

Investigational Site Number 276103

Künzing, , Germany

Investigational Site Number 276102

Oldenburg in Holstein, , Germany

Investigational Site Number 376101

Beersheba, , Israel

Investigational Site Number 376103

Petah Tikva, , Israel

Investigational Site Number 376104

Petah Tikva, , Israel

Investigational Site Number 376102

Rehovot, , Israel

Investigational Site Number 376106

Tel Aviv, , Israel

Investigational Site Number 380104

Bergamo, , Italy

Investigational Site Number 380107

Catanzaro, , Italy

Investigational Site Number 380103

Napoli, , Italy

Investigational Site Number 380108

Padua, , Italy

Investigational Site Number 380106

Partinico, , Italy

Investigational Site Number 380101

Pisa, , Italy

Investigational Site Number 380105

Roma, , Italy

Investigational Site Number 380102

Torino, , Italy

Investigational Site Number 414101

Kuwait City, , Kuwait

Investigational Site Number 422101

Beirut, , Lebanon

Investigational Site Number 422102

Hazmiyeh, , Lebanon

Investigational Site Number 578101

Oslo, , Norway

Investigational Site Number 578102

Oslo, , Norway

Investigational Site Number 752102

Gothenburg, , Sweden

Investigational Site Number 752101

Stockholm, , Sweden

Investigational Site Number 756101

Geneva, , Switzerland

Investigational Site Number 756102

Olten, , Switzerland

Investigational Site Number 756103

Reinach, , Switzerland

Investigational Site Number 792105

Adana, , Turkey (Türkiye)

Investigational Site Number 792106

Ankara, , Turkey (Türkiye)

Investigational Site Number 792102

Ankara, , Turkey (Türkiye)

Investigational Site Number 792108

Çorum, , Turkey (Türkiye)

Investigational Site Number 792109

Hatay, , Turkey (Türkiye)

Investigational Site Number 792104

Izmir, , Turkey (Türkiye)

Investigational Site Number 792101

Izmir, , Turkey (Türkiye)

Investigational Site Number 792110

Izmir, , Turkey (Türkiye)

Investigational Site Number 792107

Kayseri, , Turkey (Türkiye)

Investigational Site Number 792103

Samsun, , Turkey (Türkiye)

Investigational Site Number 784101

Dubai, , United Arab Emirates

Investigational Site Number 826104

Exeter, , United Kingdom

Investigational Site Number 826106

Manchester, , United Kingdom

Investigational Site Number 826105

Middlesbrough, , United Kingdom

Investigational Site Number 826103

Stevenage, , United Kingdom

Investigational Site Number 826101

Torquay, , United Kingdom

Investigational Site Number 826102

West Bromwich, , United Kingdom

Countries

United States; Australia; Brazil; Finland; Germany; Israel; Italy; Kuwait; Lebanon; Norway; Sweden; Switzerland; Turkey (Türkiye); United Arab Emirates; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33078867 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32035487 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31706300 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29436756 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28545518 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-001934-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1172-5262

Identifier Type: OTHER

Identifier Source: secondary_id

LPS14354

Identifier Type: -

Identifier Source: org_study_id