著者

Tamio Teramoto Masahiko Kobayashi Hiromi Tasaki Hiroaki Yagyu Toshinori Higashikata Yoshiharu Takagi Kiyoko Uno Marie T. Baccara-Dinet Atsushi Nohara

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-16-0387, (Released:2016-07-22)

参考文献数

30

被引用文献数

3 85

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Background:The ODYSSEY Japan study was designed to demonstrate the reduction in low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on to existing lipid-lowering therapy in Japanese patients with heterozygous familial hypercholesterolemia (heFH) or non-FH at high cardiovascular risk who require additional pharmacological management to achieve their LDL-C treatment goal (<2.6 or <3.1 mmol/L, depending on risk category).Methods and Results:This randomized, double-blind, parallel-group, 52-week study was conducted in Japan. Patients (n=216) with heFH, non-FH at high cardiovascular risk with coronary disease, or classified as category III were enrolled. The prespecified safety analysis was done after the last patient completed 52 weeks. Patients were randomized (2:1, alirocumab:placebo) with stratification for heFH to s.c. alirocumab (75 mg every 2 weeks [Q2 W] with increase to 150 mg if week 8 LDL-C ≥2.6/3.1 mmol/L) or placebo for 52 weeks plus stable statin therapy. At week 24, mean±SE change in LDL-C from baseline was –62.5±1.3% in the alirocumab group and 1.6±1.8% in the placebo group (difference, –64.1±2.2%; P<0.0001); the reduction was sustained to week 52 (alirocumab, –62.5±1.4%; placebo, –3.6±1.9%). No patterns were evident between treatment groups for adverse events at 52 weeks.Conclusions:In high-risk Japanese patients with hypercholesterolemia on stable statin therapy, alirocumab markedly reduced LDL-C vs. placebo and was well tolerated over 52 weeks.

著者

Tamio Teramoto Makiko Usami Yoshiharu Takagi Marie T. Baccara-Dinet for the ODYSSEY Japan Investigators

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.45070, (Released:2018-08-01)

参考文献数

39

被引用文献数

9

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Aim: To examine the efficacy and safety of alirocumab in Japanese patients with dyslipidemia with or without diabetes mellitus (DM).Methods: Patients (n=216) with heterozygous familial hypercholesterolemia (heFH), non-FH at high cardiovascular risk with coronary artery disease (CAD), or category III (primary prevention) were enrolled; 148 (68.5%) patients had a diagnosis of DM at baseline. Patients were randomized (2:1), with stratification factor (heFH, non-FH), to alirocumab (75 mg every 2 weeks [Q2W] with increase to 150 mg if week 8 LDL-C was above predefined limits) or placebo subcutaneously for 52 weeks on top of stable statin therapy.Results: At Week 24, least square (LS) mean±standard error changes in low-density lipoprotein cholesterol (LDL-C) concentration from baseline in alirocumab-treated patients were -63.1±1.6% and -60.8±2.7% in those with and without DM. These LDL-C reductions were maintained to Week 52: -63.0±1.6% (LS mean difference vs placebo -62.4±3.0%; P<0.0001) with DM and -61.3±2.8% (LS mean difference vs placebo -53.4±4.0%; P<0.0001) without DM. The most common adverse events in the alirocumab group were nasopharyngitis, back pain, injection site reaction, and fall. No particular safety signals or concerns were noted between DM and non-DM groups at 52 weeks. A dose-increase in alirocumab from 75 to 150 mg Q2W was necessary in two heFH patients, neither of whom had DM.Conclusions: In high-cardiovascular-risk Japanese patients with hypercholesterolemia on stable statin therapy, alirocumab produced substantial and sustained LDL-C reductions throughout the 52-week study regardless of DM status at baseline, with a similar safety profile to placebo.

著者

Junya Ako Kiyoshi Hibi Kenichi Tsujita Takafumi Hiro Yoshihiro Morino Ken Kozuma Toshiro Shinke Hiromasa Otake Kiyoko Uno Michael J Louie Yoshiharu Takagi Katsumi Miyauchi

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-19-0412, (Released:2019-08-20)

参考文献数

20

被引用文献数

34

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Background:In patients with acute coronary syndrome (ACS), alirocumab reduced the risk of recurring ischemic events. ODYSSEY J-IVUS assessed the effect of alirocumab on coronary atheroma volume in Japanese patients recently hospitalized with ACS and hypercholesterolemia, using intravascular ultrasound imaging analysis.Methods and Results:Patients (n=206) who at index ACS diagnosis either had low-density lipoprotein cholesterol (LDL-C) ≥2.59 mmol/L (≥100 mg/dL) despite stable statin therapy, or were not on statins with LDL-C levels above target after statin initiation, were randomized (1:1) to alirocumab (75 mg every 2 weeks [Q2 W]/up to 150 mg Q2 W), or standard of care (SoC; atorvastatin ≥10 mg/day or rosuvastatin ≥5 mg/day) for 36 weeks. The primary efficacy endpoint (week [W] 36 mean [standard error] percent change in normalized total atheroma volume [TAV] from baseline) was −3.1 (1.0)% with SoC vs. −4.8 (1.0)% with alirocumab (between-group difference: −1.6 [1.4]; P=0.23). W36 absolute change from baseline in percent atheroma volume was −1.3 (0.4)% (SoC) and −1.4 (0.4)% (alirocumab; nominal P=0.79). At W36, LDL-C was reduced from baseline by 13.4% (SoC) vs. 63.9% (alirocumab; nominal P<0.0001). In total, 61.8% (SoC) and 75.7% (alirocumab) of patients reported treatment-emergency adverse events.Conclusions:In Japanese patients with ACS and hypercholesterolemia inadequately controlled despite statin therapy, from baseline to W36, a numerically greater percent reduction in normalized TAV was observed with alirocumab vs. SoC, which did not reach statistical significance.

著者

Osamu Matsuoka Daisuke Tsuzuki Katsuhisa Suzuki Tomoyuki Tanaka Yoshiharu Takagi Philipp Oster

出版者

National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

雑誌

Japanese Journal of Infectious Diseases (ISSN:13446304)

巻号頁・発行日

pp.JJID.2020.411, (Released:2020-10-30)

参考文献数

17

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The quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (Men-ACWY-D) is licensed in Japan since 2014. An earlier registration study demonstrated the immunogenicity of one dose in Japanese adults. Immunogenicity against serogroup C was lowest. Determination of the potential to increase the serogroup C response with a second dose was of interest. This study (NCT02591290) evaluated the safety and immunogenicity of two doses administered eight weeks apart to 60 healthy Japanese adults aged 20–55 years. Blood samples were collected 28–35 days after each vaccination. Immunogenicity endpoints included seroprotection and seroconversion rates. Safety assessments included systemic adverse events (AEs), non-serious AEs, and serious AEs. Fifty-eight (96.7%) participants completed the study. Seroprotection rates for serogroups A, C, W, and Y before vaccination were 76.8%, 26.8%, 26.8%, and 50.0%, increasing to 100%, 83.9%, 91.1%, and 96.4% and 100%, 92.9%, 94.6%, and 94.6%, respectively, after two doses. Seroconversion rates for the four serogroups were 100%, 93.8%, 97.1%, and 94.1% after the first dose and 100%, 96.9%, 100%, and 100% after the second. Increases between doses were insignificant. There were no safety concerns. The two-dose series is well tolerated but clinical benefit of a second dose within 8 weeks seemed to be low.