Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale
Abstract Background Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase su...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12944-017-0513-7 |
| _version_ | 1828229654894346240 |
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| author | Tamio Teramoto Akira Kondo Arihiro Kiyosue Mariko Harada-Shiba Yasushi Ishigaki Kimimasa Tobita Yumiko Kawabata Asuka Ozaki Marie T. Baccara-Dinet Masataka Sata |
| author_facet | Tamio Teramoto Akira Kondo Arihiro Kiyosue Mariko Harada-Shiba Yasushi Ishigaki Kimimasa Tobita Yumiko Kawabata Asuka Ozaki Marie T. Baccara-Dinet Masataka Sata |
| author_sort | Tamio Teramoto |
| collection | DOAJ |
| description | Abstract Background Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). Methods The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated. Discussion The ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone). Trial registration ClinicalTrials.gov number: NCT02584504 |
| first_indexed | 2024-04-12T18:36:28Z |
| format | Article |
| id | doaj.art-21f99023cfbb491cbec1701399a79970 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-12T18:36:28Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-21f99023cfbb491cbec1701399a799702022-12-22T03:20:55ZengBMCLipids in Health and Disease1476-511X2017-06-011611810.1186/s12944-017-0513-7Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationaleTamio Teramoto0Akira Kondo1Arihiro Kiyosue2Mariko Harada-Shiba3Yasushi Ishigaki4Kimimasa Tobita5Yumiko Kawabata6Asuka Ozaki7Marie T. Baccara-Dinet8Masataka Sata9Teikyo Academic Research Center, Teikyo UniversityAsia Pacific Development, R&DDepartment of Cardiovascular Medicine, Graduate School of Medicine, University of TokyoDepartment of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research InstituteDivision of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical UniversityAsia Pacific Development, R&DSanofi JapanSanofi JapanPCSK9 Development and Launch UnitDepartment of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate SchoolAbstract Background Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). Methods The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated. Discussion The ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone). Trial registration ClinicalTrials.gov number: NCT02584504http://link.springer.com/article/10.1186/s12944-017-0513-7AlirocumabHypercholesterolemiaStatinStatin intoleranceCardiovascular riskPCSK9 inhibitor |
| spellingShingle | Tamio Teramoto Akira Kondo Arihiro Kiyosue Mariko Harada-Shiba Yasushi Ishigaki Kimimasa Tobita Yumiko Kawabata Asuka Ozaki Marie T. Baccara-Dinet Masataka Sata Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale Lipids in Health and Disease Alirocumab Hypercholesterolemia Statin Statin intolerance Cardiovascular risk PCSK9 inhibitor |
| title | Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale |
| title_full | Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale |
| title_fullStr | Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale |
| title_full_unstemmed | Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale |
| title_short | Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale |
| title_sort | efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non statin lipid lowering therapy or the lowest strength of statin odyssey nippon study design and rationale |
| topic | Alirocumab Hypercholesterolemia Statin Statin intolerance Cardiovascular risk PCSK9 inhibitor |
| url | http://link.springer.com/article/10.1186/s12944-017-0513-7 |
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