B Cariou1, L A Leiter2, D Müller-Wieland3, G Bigot4, H M Colhoun5, S Del Prato6, R R Henry7, F J Tinahones8, A Letierce9, L Aurand10, J Maroni11, K K Ray12, M Bujas-Bobanovic13. 1. Institut du thorax, CHU Nantes, INSERM, CNRS, UNIV Nantes, 44093 Nantes cedex 1, France. Electronic address: bertrand.cariou@univ.nantes.fr. 2. Li KaShing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. 3. Department of Internal Medicine I, University Hospital Aachen, Aachen, Germany. 4. IVIDATA, 92300 Levallois-Perret, France. 5. University of Edinburgh, Edinburgh, Scotland, UK. 6. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 7. University of California San Diego School of Medicine, Center for Metabolic Research, Veterans Affairs, San Diego Healthcare System, San Diego, CA, USA. 8. CIBERobn, Hospital Virgen de la Victoria, Málaga University, Spain. 9. Sanofi, 91380 Chilly-Mazarin, France. 10. Sanofi, Bridgewater, NJ, USA. 11. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 12. Department of Primary Care and Public Health, School of Public Health, Imperial College, London, UK. 13. Sanofi, 75008 Paris, France.
Abstract
AIMS: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. METHODS: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening≥70mg/dL (1.81mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24weeks of alirocumab 75mg every 2weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C≥70mg/dL at week 8 underwent a blinded dose increase to 150mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. RESULTS: This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017. CONCLUSION: The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy.
RCT Entities:
AIMS: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. METHODS: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DMpatients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening≥70mg/dL (1.81mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24weeks of alirocumab 75mg every 2weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C≥70mg/dL at week 8 underwent a blinded dose increase to 150mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. RESULTS: This is an ongoing clinical trial, with 76 T1 and 441 T2 DMpatients enrolled; results are expected in mid-2017. CONCLUSION: The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy.
Authors: Dirk Müller-Wieland; Lawrence A Leiter; Bertrand Cariou; Alexia Letierce; Helen M Colhoun; Stefano Del Prato; Robert R Henry; Francisco J Tinahones; Lisa Aurand; Jaman Maroni; Kausik K Ray; Maja Bujas-Bobanovic Journal: Cardiovasc Diabetol Date: 2017-05-25 Impact factor: 9.951
Authors: Lawrence A Leiter; Bertrand Cariou; Dirk Müller-Wieland; Helen M Colhoun; Stefano Del Prato; Francisco J Tinahones; Kausik K Ray; Maja Bujas-Bobanovic; Catherine Domenger; Jonas Mandel; Rita Samuel; Robert R Henry Journal: Diabetes Obes Metab Date: 2017-10-10 Impact factor: 6.577