Clinical trial NCT02585778: 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)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab in Insulin Treated Patients With Type 1 or Type 2 Diabetes and With Hypercholesterolemia at High Cardiovascular Risk Not Adequately Controlled on Maximally Tolerated LDL-C Lowering Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolaemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2015-10-23
Enrollment: 517
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 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).

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.

Eligibility criteria: Inclusion criteria:

* 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
* 18 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

Exclusion criteria:

* 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.

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
measure: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)
timeFrame: From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)
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 Measured LDL-C at Week 24 - ITT 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 Measured LDL-C at Week 12 - ITT 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 Apolipoprotein B (Apo-B) at Week 24 - ITT 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: 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: Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL 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 LDL-C Particle Number at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis
timeFrame: Baseline, Weeks 12 and 24
measure: Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis
timeFrame: Baseline, Weeks 12 and 24
measure: Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis
timeFrame: Baseline, Weeks 12 and 24
measure: Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis
timeFrame: Baseline, Weeks 12 and 24
measure: Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis
timeFrame: Baseline, Weeks 12 and 24
measure: Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis
timeFrame: Baseline, Weeks 12 and 24
measure: Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis
timeFrame: Baseline, Weeks 12 and 24
measure: Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis
timeFrame: Baseline, Weeks 12 and 24
measure: Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis
timeFrame: Baseline, Weeks 12 and 24
measure: Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis
timeFrame: Baseline, Weeks 12 and 24
Other outcomes:
Locations:
city: Encino
country: United States
facility: Investigational Site Number 840020
state: California
city: Fresno
country: United States
facility: Investigational Site Number 840002
state: California
city: Oakland
country: United States
facility: Investigational Site Number 840029
state: California
city: Loveland
country: United States
facility: Investigational Site Number 840027
state: Colorado
city: Atlantis
country: United States
facility: Investigational Site Number 840026
state: Florida
city: Bradenton
country: United States
facility: Investigational Site Number 840006
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840023
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 840028
state: Florida
city: Ponte Vedra Beach
country: United States
facility: Investigational Site Number 840022
state: Florida
city: Roswell
country: United States
facility: Investigational Site Number 840021
state: Georgia
city: Springfield
country: United States
facility: Investigational Site Number 840007
state: Illinois
city: Indianapolis
country: United States
facility: Investigational Site Number 840011
state: Indiana
city: Valparaiso
country: United States
facility: Investigational Site Number 840015
state: Indiana
city: Des Moines
country: United States
facility: Investigational Site Number 840010
state: Iowa
city: Louisville
country: United States
facility: Investigational Site Number 840005
state: Kentucky
city: Auburn
country: United States
facility: Investigational Site Number 840018
state: Maine
city: Hyattsville
country: United States
facility: Investigational Site Number 840013
state: Maryland
city: Rockville
country: United States
facility: Investigational Site Number 840016
state: Maryland
city: Minneapolis
country: United States
facility: Investigational Site Number 840004
state: Minnesota
city: Jamaica
country: United States
facility: Investigational Site Number 840012
state: New York
city: Maumee
country: United States
facility: Investigational Site Number 840014
state: Ohio
city: Greer
country: United States
facility: Investigational Site Number 840009
state: South Carolina
city: Chattanooga
country: United States
facility: Investigational Site Number 840024
state: Tennessee
city: Austin
country: United States
facility: Investigational Site Number 840001
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840003
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840019
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840025
state: Texas
city: Ogden
country: United States
facility: Investigational Site Number 840017
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Site Number 840008
state: Utah
city: Innsbruck
country: Austria
facility: Investigational Site Number 040002
city: Linz
country: Austria
facility: Investigational Site Number 040005
city: Salzburg
country: Austria
facility: Investigational Site Number 040003
city: Salzburg
country: Austria
facility: Investigational Site Number 040004
city: Wien
country: Austria
facility: Investigational Site Number 040001
city: Edegem
country: Belgium
facility: Investigational Site Number 056002
city: Haine-Saint-Paul
country: Belgium
facility: Investigational Site Number 056003
city: Leuven
country: Belgium
facility: Investigational Site Number 056001
city: Besancon
country: France
facility: Investigational Site Number 250-008
city: Corbeil Essonnes
country: France
facility: Investigational Site Number 250-005
city: La Rochelle Cedex 1
country: France
facility: Investigational Site Number 250-004
city: Le Creusot
country: France
facility: Investigational Site Number 250-003
city: Mulhouse
country: France
facility: Investigational Site Number 250-009
city: Nantes cedex 01
country: France
facility: Investigational Site Number 250-002
city: Paris
country: France
facility: Investigational Site Number 250-007
city: Strasbourg Cedex 2
country: France
facility: Investigational Site Number 250-006
city: TOULOUSE Cedex 9
country: France
facility: Investigational Site Number 250-001
city: Aschaffenburg
country: Germany
facility: Investigational Site Number 276015
city: Berlin
country: Germany
facility: Investigational Site Number 276002
city: Dortmund
country: Germany
facility: Investigational Site Number 276011
city: Dresden
country: Germany
facility: Investigational Site Number 276019
city: Dresden
country: Germany
facility: Investigational Site Number 276014
city: Dresden
country: Germany
facility: Investigational Site Number 276009
city: Hamburg
country: Germany
facility: Investigational Site Number 276021
city: Hamburg
country: Germany
facility: Investigational Site Number 276018
city: Heidelberg
country: Germany
facility: Investigational Site Number 276005
city: Lüneburg
country: Germany
facility: Investigational Site Number 276013
city: Magdeburg
country: Germany
facility: Investigational Site Number 276022
city: Neumünster
country: Germany
facility: Investigational Site Number 276008
city: Neuwied
country: Germany
facility: Investigational Site Number 276017
city: Oldenburg
country: Germany
facility: Investigational Site Number 276004
city: Pirna
country: Germany
facility: Investigational Site Number 276003
city: Riesa
country: Germany
facility: Investigational Site Number 276006
city: Saarlouis
country: Germany
facility: Investigational Site Number 276010
city: Sulzbach-Rosenberg
country: Germany
facility: Investigational Site Number 276016
city: Catania
country: Italy
facility: Investigational Site Number 380004
city: Catanzaro
country: Italy
facility: Investigational Site Number 380003
city: Como
country: Italy
facility: Investigational Site Number 380011
city: Milano
country: Italy
facility: Investigational Site Number 380006
city: Milano
country: Italy
facility: Investigational Site Number 380007
city: Moncalieri
country: Italy
facility: Investigational Site Number 380005
city: Napoli
country: Italy
facility: Investigational Site Number 380009
city: Padova
country: Italy
facility: Investigational Site Number 380008
city: Palermo
country: Italy
facility: Investigational Site Number 380002
city: Pisa
country: Italy
facility: Investigational Site Number 380001
city: Roma
country: Italy
facility: Investigational Site Number 380010
city: Verona
country: Italy
facility: Investigational Site Number 380012
city: Apeldoorn
country: Netherlands
facility: Investigational Site Number 528002
city: Groningen
country: Netherlands
facility: Investigational Site Number 528005
city: Hoogeveen
country: Netherlands
facility: Investigational Site Number 528003
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528001
city: Utrecht
country: Netherlands
facility: Investigational Site Number 528004
city: Badalona
country: Spain
facility: Investigational Site Number 724007
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Ferrol
country: Spain
facility: Investigational Site Number 724006
city: Granada
country: Spain
facility: Investigational Site Number 724013
city: Madrid
country: Spain
facility: Investigational Site Number 724005
city: Madrid
country: Spain
facility: Investigational Site Number 724004
city: Majadahonda
country: Spain
facility: Investigational Site Number 724011
city: Málaga
country: Spain
facility: Investigational Site Number 724008
city: Oviedo
country: Spain
facility: Investigational Site Number 724014
city: Palma de Mallorca
country: Spain
facility: Investigational Site Number 724009
city: Pamplona
country: Spain
facility: Investigational Site Number 724002
city: Sant Joan Despí
country: Spain
facility: Investigational Site Number 724010
city: Segovia
country: Spain
facility: Investigational Site Number 724012
city: Sevilla
country: Spain
facility: Investigational Site Number 724003
city: Olten
country: Switzerland
facility: Investigational Site Number 756001
city: St. Gallen
country: Switzerland
facility: Investigational Site Number 756003
city: Airdrie
country: United Kingdom
facility: Investigational Site Number 826010
city: Bath
country: United Kingdom
facility: Investigational Site Number 826011
city: Bournemouth
country: United Kingdom
facility: Investigational Site Number 826009
city: Bradford
country: United Kingdom
facility: Investigational Site Number 826005
city: Bristol
country: United Kingdom
facility: Investigational Site Number 826004
city: Burton On Trent
country: United Kingdom
facility: Investigational Site Number 826001
city: Durham
country: United Kingdom
facility: Investigational Site Number 826015
city: High Wycombe
country: United Kingdom
facility: Investigational Site Number 826012
city: Manchester
country: United Kingdom
facility: Investigational Site Number 826007
city: Peterborough
country: United Kingdom
facility: Investigational Site Number 826006
city: Southampton
country: United Kingdom
facility: Investigational Site Number 826003
city: Truro
country: United Kingdom
facility: Investigational Site Number 826008
city: Welwyn Garden City
country: United Kingdom
facility: Investigational Site Number 826002
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: 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: 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.