Abstract:
OBJECTIVES:The aim of this study was to evaluate the efficacy and safety of mipomersen in hypercholesterolemic subjects taking stable statin therapy. BACKGROUND:Mipomersen is an apolipoprotein (apo) B synthesis inhibitor that has demonstrated significant reductions in apo B and low-density lipoprotein (LDL) cholesterol in Phase 1 clinical trials in healthy volunteers. METHODS:A randomized, placebo-controlled, dose-escalation Phase 2 study was designed to evaluate the effects of mipomersen in hypercholesterolemic subjects taking stable statin therapy. Seventy-four subjects were enrolled sequentially into 1 of 6 dose cohorts at a 4:1 (active/placebo) ratio. Subjects received 7 doses of 30 to 400 mg over 5 weeks in the first 5 cohorts and 15 doses of 200 mg over 13 weeks in the sixth cohort. Pre-specified end points included percentage change from baseline in apo B and LDL cholesterol. Safety was assessed with laboratory test results and by the incidence and severity of adverse events. RESULTS:The apo B and LDL cholesterol were reduced by 19% to 54% and 21% to 52%, respectively, at doses of 100 mg/week mipomersen and higher in the 5-week treatment cohorts. Efficacy seemed to increase upon treatment for 13 weeks at a dose of 200 mg/week. Injection site reactions (mild to moderate erythema [90%]) and hepatic transaminase increases (17%) were the most common adverse events, leading to discontinuation in 2 subjects and 1 subject, respectively. In the 13-week treatment cohort, 5 of 10 subjects (50%) had elevations >or=3x the upper limit of normal, 4 of which persisted on 2 consecutive occasions. CONCLUSIONS:Mipomersen might hold promise for treatment of patients not reaching target LDL cholesterol levels on stable statin therapy. Further studies are needed to address the mechanisms and clinical relevance of transaminase changes after mipomersen administration. (Dose-Escalating Safety Study in Subjects on Stable Statin Therapy; NCT00231569).
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Akdim F,Stroes ES,Sijbrands EJ,Tribble DL,Trip MD,Jukema JW,Flaim JD,Su J,Yu R,Baker BF,Wedel MK,Kastelein JJdoi
10.1016/j.jacc.2009.11.069subject
Has Abstractpub_date
2010-04-13 00:00:00pages
1611-8issue
15eissn
0735-1097issn
1558-3597pii
S0735-1097(10)00451-1journal_volume
55pub_type
杂志文章,多中心研究,随机对照试验abstract::The incidence of left atrial spontaneous echo contrast was evaluated in 52 patients with isolated or predominant mitral valve stenosis (Group 1) and 70 other patients who had undergone mitral valve replacement (Group 2). All patients were studied by conventional transthoracic and transesophageal two-dimensional echoca...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(88)90283-5
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abstract:BACKGROUND:Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk. OBJECTIVES:The authors performed echocardiogra...
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journal_title:Journal of the American College of Cardiology
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doi:10.1016/s0735-1097(84)80354-x
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abstract:OBJECTIVES:We sought to examine the association of apolipoprotein (apo) E genotypes with baseline plasma lipid levels and severity of coronary artery disease (CAD), as well as the response to treatment with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). BACKGROUND:Apo E genotypes have been a...
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pub_type: 临床试验,杂志文章
doi:10.1016/s0735-1097(00)00918-9
更新日期:2000-11-01 00:00:00
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journal_title:Journal of the American College of Cardiology
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更新日期:1999-01-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2011.05.063
更新日期:2011-11-15 00:00:00
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doi:10.1016/j.jacc.2019.09.041
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doi:10.1016/s0735-1097(01)01766-1
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journal_title:Journal of the American College of Cardiology
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doi:10.1016/j.jacc.2012.01.063
更新日期:2012-06-12 00:00:00
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doi:10.1016/j.jacc.2009.12.062
更新日期:2010-06-08 00:00:00
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doi:10.1016/j.jacc.2003.10.037
更新日期:2004-03-17 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章
doi:10.1016/j.jacc.2012.09.059
更新日期:2013-02-12 00:00:00
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journal_title:Journal of the American College of Cardiology
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
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更新日期:2013-09-10 00:00:00
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更新日期:2000-11-15 00:00:00
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journal_title:Journal of the American College of Cardiology
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,多中心研究
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更新日期:2019-03-05 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
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更新日期:2003-03-05 00:00:00
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journal_title:Journal of the American College of Cardiology
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更新日期:1997-05-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
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更新日期:1996-03-01 00:00:00