Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials

 

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dc.contributor.author Colhoun, Helen M
dc.contributor.author Robinson, Jennifer G
dc.contributor.author Farnier, Michel
dc.contributor.author Cariou, Bertrand
dc.contributor.author Blom, Dirk
dc.contributor.author Kereiakes, Dean J
dc.contributor.author Lorenzato, Christelle
dc.contributor.author Pordy, Robert
dc.contributor.author Chaudhari, Umesh
dc.date.accessioned 2015-07-30T03:58:48Z
dc.date.available 2015-07-30T03:58:48Z
dc.date.issued 2014-09-20
dc.identifier.citation Colhoun, H. M., Robinson, J. G., Farnier, M., Cariou, B., Blom, D., Kereiakes, D. J., ... & Chaudhari, U. (2014). Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. BMC cardiovascular disorders, 14(1), 121.
dc.identifier.uri http://hdl.handle.net/11427/13603
dc.identifier.uri http://dx.doi.org/10.1186/1471-2261-14-121
dc.description.abstract Abstract Background Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9) under investigation for treatment of hypercholesterolemia and reduction of cardiovascular events. Methods/design The COMBO studies, part of the Phase 3 ODYSSEY clinical trial program, are designed to evaluate the efficacy and safety of alirocumab as add-on therapy to stable, maximally tolerated daily statin, with or without other lipid-lowering therapy (LLT), in a planned 966 patients with hypercholesterolemia at high cardiovascular risk. COMBO I ( http://clinicaltrials.gov/show/NCT01644175 ) is placebo-controlled, with a double-blind treatment period of 52 weeks, and 306 planned patients who may receive other LLTs in addition to statin therapy. COMBO II ( http://clinicaltrials.gov/show/NCT01644188 ) has a double-blind treatment period of 104 weeks, comparing alirocumab with ezetimibe in 660 planned patients receiving statin therapy (but no other LLTs). The primary efficacy endpoint is the difference between treatment arms in percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 24. Both studies utilized a starting dose of alirocumab 75 mg every 2 weeks (Q2W; administered as 1 mL solution via auto-injector). Patients with LDL-C levels ≥70 mg/dL after 8 weeks of treatment were up-titrated in a blinded manner at week 12 to alirocumab 150 mg Q2W (also 1 mL auto-injector). Discussion In conclusion, the COMBO studies will provide information on the long-term efficacy and safety of alirocumab in high-risk patients when administered in addition to maximally tolerated statin therapy, with a flexible dosing strategy which allows for individualized therapy based on the degree of LDL-C lowering needed to achieve the desired treatment response. Trial registrations COMBO I: NCT01644175 ( NCT01644175 ). COMBO II: NCT01644188 ( NCT01644188 ).
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License *
dc.rights.uri http://creativecommons.org/licenses/by/4.0 *
dc.source BMC Cardiovascular Disorders en_ZA
dc.source.uri http://www.biomedcentral.com/bmccardiovascdisord/
dc.subject.other Alirocumab en_ZA
dc.subject.other Ezetimibe en_ZA
dc.subject.other Low-density lipoprotein cholesterol en_ZA
dc.subject.other Monoclonal antibody en_ZA
dc.subject.other Proprotein convertase subtilisin kexin type 9 en_ZA
dc.title Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials
dc.type Journal Article en_ZA
dc.date.updated 2015-01-15T17:56:52Z
dc.language.rfc3066 en
dc.rights.holder Colhoun et al.; licensee BioMed Central Ltd.
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Lipidology en_ZA
uct.type.filetype
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Colhoun, H. M., Robinson, J. G., Farnier, M., Cariou, B., Blom, D., Kereiakes, D. J., ... Chaudhari, U. (2014). Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. <i>BMC Cardiovascular Disorders</i>, http://hdl.handle.net/11427/13603 en_ZA
dc.identifier.chicagocitation Colhoun, Helen M, Jennifer G Robinson, Michel Farnier, Bertrand Cariou, Dirk Blom, Dean J Kereiakes, Christelle Lorenzato, Robert Pordy, and Umesh Chaudhari "Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials." <i>BMC Cardiovascular Disorders</i> (2014) http://hdl.handle.net/11427/13603 en_ZA
dc.identifier.vancouvercitation Colhoun HM, Robinson JG, Farnier M, Cariou B, Blom D, Kereiakes DJ, et al. Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. BMC Cardiovascular Disorders. 2014; http://hdl.handle.net/11427/13603. en_ZA
dc.identifier.ris TY - Journal Article AU - Colhoun, Helen M AU - Robinson, Jennifer G AU - Farnier, Michel AU - Cariou, Bertrand AU - Blom, Dirk AU - Kereiakes, Dean J AU - Lorenzato, Christelle AU - Pordy, Robert AU - Chaudhari, Umesh AB - Abstract Background Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9) under investigation for treatment of hypercholesterolemia and reduction of cardiovascular events. Methods/design The COMBO studies, part of the Phase 3 ODYSSEY clinical trial program, are designed to evaluate the efficacy and safety of alirocumab as add-on therapy to stable, maximally tolerated daily statin, with or without other lipid-lowering therapy (LLT), in a planned 966 patients with hypercholesterolemia at high cardiovascular risk. COMBO I ( http://clinicaltrials.gov/show/NCT01644175 ) is placebo-controlled, with a double-blind treatment period of 52 weeks, and 306 planned patients who may receive other LLTs in addition to statin therapy. COMBO II ( http://clinicaltrials.gov/show/NCT01644188 ) has a double-blind treatment period of 104 weeks, comparing alirocumab with ezetimibe in 660 planned patients receiving statin therapy (but no other LLTs). The primary efficacy endpoint is the difference between treatment arms in percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 24. Both studies utilized a starting dose of alirocumab 75 mg every 2 weeks (Q2W; administered as 1 mL solution via auto-injector). Patients with LDL-C levels ≥70 mg/dL after 8 weeks of treatment were up-titrated in a blinded manner at week 12 to alirocumab 150 mg Q2W (also 1 mL auto-injector). Discussion In conclusion, the COMBO studies will provide information on the long-term efficacy and safety of alirocumab in high-risk patients when administered in addition to maximally tolerated statin therapy, with a flexible dosing strategy which allows for individualized therapy based on the degree of LDL-C lowering needed to achieve the desired treatment response. Trial registrations COMBO I: NCT01644175 ( NCT01644175 ). COMBO II: NCT01644188 ( NCT01644188 ). DA - 2014-09-20 DB - OpenUCT DO - 10.1186/1471-2261-14-121 DP - University of Cape Town J1 - BMC Cardiovascular Disorders LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials TI - Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials UR - http://hdl.handle.net/11427/13603 ER - en_ZA


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