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

Cardiovascular Diabetology

Study Protocol

Alexia Letierce¹  Francisco J. Tinahones²  Stefano Del Prato³  Dirk Müller-Wieland⁴  Kausik K. Ray⁵  Bertrand Cariou⁶  Lawrence A. Leiter⁷  Jaman Maroni⁸  Lisa Aurand⁹  Maja Bujas-Bobanovic^1,10  Robert R. Henry^1,11  Helen M. Colhoun^1,12 

[1] Biostatistics and Programming Department, Sanofi, Chilly-Mazarin, France;CIBERobn, Hospital Virgen de la Victoria, Málaga University, Málaga, Spain;Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;Department of Internal Medicine I, University Hospital Aachen, Pauwelsstr. 30, 52074, Aachen, Germany;Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London, UK;Institut du Thorax, CHU Nantes, Nantes, France;Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada;Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA;Sanofi, Bridgewater, NJ, USA;Sanofi, Paris, France;University of California San Diego School of Medicine, Center for Metabolic Research, Veterans Affairs, San Diego Healthcare System, San Diego, CA, USA;University of Edinburgh, Edinburgh, Scotland, UK;

关键词: Alirocumab;    PCSK9;    Diabetes;    Mixed dyslipidaemia;    Non-HDL-C;    ODYSSEY;   

DOI  :  10.1186/s12933-017-0552-4

 received in 2017-03-09, accepted in 2017-05-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundType 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator.MethodsDM-DYSLIPIDEMIA is a Phase 3b/4, randomised, open-label, parallel group, multinational study that planned to enrol 420 individuals. Main inclusion criteria were T2DM and mixed dyslipidaemia (non-HDL-C ≥100 mg/dl [≥2.59 mmol/l], and triglycerides ≥150 and <500 mg/dl [≥1.70 and <5.65 mmol/l]) with documented atherosclerotic cardiovascular disease or ≥1 additional cardiovascular risk factor. Participants were randomised (2:1) to alirocumab 75 mg every 2 weeks (Q2W) or lipid-lowering usual care on top of maximally tolerated statin (or no statin if intolerant). If randomised to usual care, investigators were able to add their pre-specified choice of one of the following to the patient’s current statin regimen: ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid, in accordance with local standard-of-care. Alirocumab-treated individuals with non-HDL-C ≥100 mg/dl at week 8 will undergo a blinded dose increase to 150 mg Q2W at week 12. The primary efficacy endpoint is non-HDL-C change from baseline to week 24 with alirocumab versus usual care; other lipid levels (including LDL-C), glycaemia-related measures, safety and tolerability will also be assessed. Alirocumab will be compared to fenofibrate in a secondary analysis.ResultsRecruitment completed with 413 individuals randomised in 14 countries worldwide. Results of this trial are expected in the second quarter of 2017.ConclusionsODYSSEY DM-DYSLIPIDEMIA will provide information on the efficacy and safety of alirocumab versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk using non-HDL-C as the primary efficacy endpoint.Trial registration NCT02642159 (registered December 24, 2015)

【 授权许可】

CC BY   
© The Author(s) 2017