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.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.date.updated | 2015-01-15T17:56:52Z | |
| 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.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.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.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 |
| dc.identifier.uri | http://hdl.handle.net/11427/13603 | |
| dc.identifier.uri | http://dx.doi.org/10.1186/1471-2261-14-121 | |
| 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.language.rfc3066 | en | |
| dc.publisher.department | Division of Lipidology | en_ZA |
| dc.publisher.faculty | Faculty of Health Sciences | en_ZA |
| dc.publisher.institution | University of Cape Town | |
| dc.rights | This is an Open Access article distributed under the terms of the Creative Commons Attribution License | * |
| dc.rights.holder | Colhoun et al.; licensee BioMed Central Ltd. | |
| 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 |
| uct.type.filetype | ||
| uct.type.filetype | Text | |
| uct.type.filetype | Image | |
| uct.type.publication | Research | en_ZA |
| uct.type.resource | Article | en_ZA |