Clinical trial NCT02642159: 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)
Official title: A Randomized, Open-Label, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab Versus Usual Care in Patients With Type 2 Diabetes and Mixed Dyslipidemia at High Cardiovascular Risk With Non-HDL-C Not Adequately Controlled With Maximally Tolerated Statin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dyslipidemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2015-12-30
Enrollment: 413
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: 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.

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.

Primary outcomes:
measure: Percent Change From Baseline in Non-HDL-C at Week 24: Overall Intent-to-treat (ITT) Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Percent Change From Baseline in Measured Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24: Overall ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Measured LDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 12: Overall ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Measured LDL-C at Week 12: Overall ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Measured LDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24: Overall ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 : Overall ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein(a) at Week 24 : Overall ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein(a) at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 24: Overall ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 24 : Overall ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in LDL-C Particle Number at Week 24: Overall ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in LDL-C Particle Number at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum
timeFrame: From Baseline to Week 24
measure: Absolute Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 and 24 : Overall ITT Analysis
timeFrame: Baseline, Week 12 and 24
measure: Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 and 24 : Overall ITT Analysis
timeFrame: Baseline, Week 12 and 24
measure: Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Week 12 and 24 : Overall ITT Analysis
timeFrame: Baseline, Week 12 and 24
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Investigational Site Number 840-163
state: Arkansas
city: Fresno
country: United States
facility: Investigational Site Number 840-141
state: California
city: Huntington Beach
country: United States
facility: Investigational Site Number 840-152
state: California
city: La Jolla
country: United States
facility: Investigational Site Number 840-115
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840-118
state: California
city: Northridge
country: United States
facility: Investigational Site Number 840-106
state: California
city: Port Hueneme
country: United States
facility: Investigational Site Number 840-176
state: California
city: Tarzana
country: United States
facility: Investigational Site Number 840-122
state: California
city: Tustin
country: United States
facility: Investigational Site Number 840-156
state: California
city: Van Nuys
country: United States
facility: Investigational Site Number 840-160
state: California
city: Boca Raton
country: United States
facility: Investigational Site Number 840-107
state: Florida
city: Boynton Beach
country: United States
facility: Investigational Site Number 840-170
state: Florida
city: Bradenton
country: United States
facility: Investigational Site Number 840-114
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 840-132
state: Florida
city: Oviedo
country: United States
facility: Investigational Site Number 840-179
state: Florida
city: Tampa
country: United States
facility: Investigational Site Number 840-123
state: Florida
city: Bainbridge
country: United States
facility: Investigational Site Number 840-137
state: Georgia
city: Columbus
country: United States
facility: Investigational Site Number 840-128
state: Georgia
city: Stockbridge
country: United States
facility: Investigational Site Number 840-169
state: Georgia
city: Idaho Falls
country: United States
facility: Investigational Site Number 840-167
state: Idaho
city: Chicago
country: United States
facility: Investigational Site Number 840-161
state: Illinois
city: Crystal Lake
country: United States
facility: Investigational Site Number 840-184
state: Illinois
city: Evanston
country: United States
facility: Investigational Site Number 840-174
state: Illinois
city: Springfield
country: United States
facility: Investigational Site Number 840-138
state: Illinois
city: Louisville
country: United States
facility: Investigational Site Number 840-108
state: Kentucky
city: Paducah
country: United States
facility: Investigational Site Number 840-183
state: Kentucky
city: Metairie
country: United States
facility: Investigational Site Number 840-190
state: Louisiana
city: Rockville
country: United States
facility: Investigational Site Number 840-151
state: Maryland
city: Jefferson City
country: United States
facility: Investigational Site Number 840-113
state: Missouri
city: Saint Louis
country: United States
facility: Investigational Site Number 840-120
state: Missouri
city: Omaha
country: United States
facility: Investigational Site Number 840-148
state: Nebraska
city: Las Vegas
country: United States
facility: Investigational Site Number 840-101
state: Nevada
city: Las Vegas
country: United States
facility: Investigational Site Number 840-140
state: Nevada
city: Albany
country: United States
facility: Investigational Site Number 840-178
state: New York
city: New York
country: United States
facility: Investigational Site Number 840-181
state: New York
city: New York
country: United States
facility: Investigational Site Number 840-157
state: New York
city: Greensboro
country: United States
facility: Investigational Site Number 840-188
state: North Carolina
city: Morehead City
country: United States
facility: Investigational Site Number 840-131
state: North Carolina
city: Morganton
country: United States
facility: Investigational Site Number 840-158
state: North Carolina
city: Fargo
country: United States
facility: Investigational Site Number 840-129
state: North Dakota
city: Columbus
country: United States
facility: Investigational Site Number 840-104
state: Ohio
city: Marion
country: United States
facility: Investigational Site Number 840-105
state: Ohio
city: Maumee
country: United States
facility: Investigational Site Number 840-175
state: Ohio
city: Bend
country: United States
facility: Investigational Site Number 840-136
state: Oregon
city: Murrells Inlet
country: United States
facility: Investigational Site Number 840-187
state: South Carolina
city: Summerville
country: United States
facility: Investigational Site Number 840-111
state: South Carolina
city: Chattanooga
country: United States
facility: Investigational Site Number 840-147
state: Tennessee
city: Knoxville
country: United States
facility: Investigational Site Number 840-159
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site Number 840-153
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840-143
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840-168
state: Texas
city: Round Rock
country: United States
facility: Investigational Site Number 840-142
state: Texas
city: Tomball
country: United States
facility: Investigational Site Number 840-133
state: Texas
city: Orem
country: United States
facility: Investigational Site Number 840-185
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Site Number 840-150
state: Utah
city: Chesapeake
country: United States
facility: Investigational Site Number 840-126
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 840-171
state: Virginia
city: Herston
country: Australia
facility: Investigational Site Number 036102
city: Merewether
country: Australia
facility: Investigational Site Number 036104
city: St Leonards
country: Australia
facility: Investigational Site Number 036101
city: Campinas
country: Brazil
facility: Investigational Site Number 076103
city: Fortaleza
country: Brazil
facility: Investigational Site Number 076104
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076101
city: São paulo
country: Brazil
facility: Investigational Site Number 076105
city: São Paulo
country: Brazil
facility: Investigational Site Number 076106
city: SãO Paulo
country: Brazil
facility: Investigational Site Number 076102
city: Oulu
country: Finland
facility: Investigational Site Number 246102
city: Oulu
country: Finland
facility: Investigational Site Number 246101
city: Tampere
country: Finland
facility: Investigational Site Number 246104
city: Berlin
country: Germany
facility: Investigational Site Number 276112
city: Berlin
country: Germany
facility: Investigational Site Number 276109
city: Dippoldiswalde
country: Germany
facility: Investigational Site Number 276104
city: Dresden
country: Germany
facility: Investigational Site Number 276101
city: Essen
country: Germany
facility: Investigational Site Number 276110
city: Essen
country: Germany
facility: Investigational Site Number 276108
city: Goch
country: Germany
facility: Investigational Site Number 276111
city: Karlsruhe
country: Germany
facility: Investigational Site Number 276107
city: Künzing
country: Germany
facility: Investigational Site Number 276103
city: Oldenburg in Holstein
country: Germany
facility: Investigational Site Number 276102
city: Beer Sheva
country: Israel
facility: Investigational Site Number 376101
city: Petach Tikva
country: Israel
facility: Investigational Site Number 376103
city: Petach tikva
country: Israel
facility: Investigational Site Number 376104
city: Rehovot
country: Israel
facility: Investigational Site Number 376102
city: Tel-Aviv
country: Israel
facility: Investigational Site Number 376106
city: Bergamo
country: Italy
facility: Investigational Site Number 380104
city: Catanzaro
country: Italy
facility: Investigational Site Number 380107
city: Napoli
country: Italy
facility: Investigational Site Number 380103
city: Padova
country: Italy
facility: Investigational Site Number 380108
city: Partinico
country: Italy
facility: Investigational Site Number 380106
city: Pisa
country: Italy
facility: Investigational Site Number 380101
city: Roma
country: Italy
facility: Investigational Site Number 380105
city: Torino
country: Italy
facility: Investigational Site Number 380102
city: Kuwait
country: Kuwait
facility: Investigational Site Number 414101
city: Beirut
country: Lebanon
facility: Investigational Site Number 422101
city: Hazmieh
country: Lebanon
facility: Investigational Site Number 422102
city: Oslo
country: Norway
facility: Investigational Site Number 578101
city: Oslo
country: Norway
facility: Investigational Site Number 578102
city: Göteborg
country: Sweden
facility: Investigational Site Number 752102
city: Stockholm
country: Sweden
facility: Investigational Site Number 752101
city: Genève
country: Switzerland
facility: Investigational Site Number 756101
city: Olten
country: Switzerland
facility: Investigational Site Number 756102
city: Reinach
country: Switzerland
facility: Investigational Site Number 756103
city: Adana
country: Turkey
facility: Investigational Site Number 792105
city: Ankara
country: Turkey
facility: Investigational Site Number 792106
city: Ankara
country: Turkey
facility: Investigational Site Number 792102
city: Corum
country: Turkey
facility: Investigational Site Number 792108
city: Hatay
country: Turkey
facility: Investigational Site Number 792109
city: Izmir
country: Turkey
facility: Investigational Site Number 792104
city: Izmir
country: Turkey
facility: Investigational Site Number 792101
city: Izmir
country: Turkey
facility: Investigational Site Number 792110
city: Kayseri
country: Turkey
facility: Investigational Site Number 792107
city: Samsun
country: Turkey
facility: Investigational Site Number 792103
city: Dubai
country: United Arab Emirates
facility: Investigational Site Number 784101
city: Exeter
country: United Kingdom
facility: Investigational Site Number 826104
city: Manchester
country: United Kingdom
facility: Investigational Site Number 826106
city: Middlesborough
country: United Kingdom
facility: Investigational Site Number 826105
city: Stevenage
country: United Kingdom
facility: Investigational Site Number 826103
city: Torquay
country: United Kingdom
facility: Investigational Site Number 826101
city: West Bromwich
country: United Kingdom
facility: Investigational Site Number 826102
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.