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 riskReport as inadecuate




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 - Download this document for free, or read online. Document in PDF available to download.

Cardiovascular Diabetology

, 16:70

First Online: 25 May 2017Received: 09 March 2017Accepted: 15 May 2017DOI: 10.1186-s12933-017-0552-4

Cite this article as: Müller-Wieland, D., Leiter, L.A., Cariou, B. et al. Cardiovasc Diabetol 2017 16: 70. doi:10.1186-s12933-017-0552-4

Abstract

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

KeywordsAlirocumab PCSK9 Diabetes Mixed dyslipidaemia Non-HDL-C ODYSSEY AbbreviationsApoapolipoprotein

DMdiabetes mellitus

FPGfasting plasma glucose

HbA1cglycated haemoglobin

HDL-Chigh-density lipoprotein cholesterol

IDLintermediate-density lipoprotein

I-TAQinjection-treatment acceptance questionnaire

ITTintent-to-treat

LDLlow-density lipoprotein

LDL-Clow-density lipoprotein cholesterol

LDL-Plow-density lipoprotein particle

LDLRlow-density lipoprotein receptor

Lpalipoproteina

MMRMmixed effect model with repeated measures

non-HDL-Cnon-high-density lipoprotein cholesterol

PCSK9proprotein convertase subtilisin-kexin type 9

Q2Wevery 2 weeks

SDstandard deviation

T2DMtype 2 diabetes mellitus

TCtotal cholesterol

TEAEtreatment-emergent adverse events

TGtriglyceride

TRLtriglyceride-rich lipoprotein

VLDLvery low-density lipoprotein

Electronic supplementary materialThe online version of this article doi:10.1186-s12933-017-0552-4 contains supplementary material, which is available to authorized users.





Author: Dirk Müller-Wieland - Lawrence A. Leiter - Bertrand Cariou - Alexia Letierce - Helen M. Colhoun - Stefano Del Prato - Ro

Source: https://link.springer.com/







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