کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3492361 1234186 2017 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 stu
ترجمه فارسی عنوان
خودکارآمدی، ایمنی و تحمل یک آنتی بادی مونوکلونال برای proprotein convertase subtilisin / kexin نوع 9 در ترکیب با استاتین در بیماران مبتلا به هیپرکلسترولمی (لاپلاس-TIMI 57): یک کارآزمایی بالینی تصادفی کنترل شده با پلاسبو، دامنه دوز ، فاز 2 STU
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی و دندانپزشکی (عمومی)
چکیده انگلیسی

SummaryBackgroundLDL cholesterol (LDL-C) is a well established risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds LDL receptors, targeting them for degradation. We therefore assessed the efficacy, safety, and tolerability of AMG 145, a human monoclonal IgG2 antibody against PCSK9, in stable patients with hypercholesterolemia on a statin.MethodsIn a phase 2, dose-ranging study done in 78 centres in the USA, Canada, Denmark, Hungary, and Czech Republic, patients (aged 18–80 years) with LDL-C greater than 2·2 mmol/L on a stable dose of statin (with or without ezetimibe), were randomly assigned equally, through an interactive voice response system, to subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, or matching placebo every 2 weeks; or subcutaneous injections of AMG 145 280 mg, 350 mg, or 420 mg, or matching placebo every 4 weeks. Everyone was masked to treatment assignment within the every 2 weeks and every 4 weeks schedules. The primary endpoint was the percentage change in LDL-C concentration from baseline after 12 weeks. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01380730.Findings631 patients with hypercholesterolaemia were randomly assigned to AMG 145 70 mg (n=79), 105 mg (n=79), or 140 mg (n=78), or matching placebo (n=78) every 2 weeks; or AMG 145 280 mg (n=79), 350 mg (n=79), and 420 mg (n=80), and matching placebo (n=79) every 4 weeks. At the end of the dosing interval at week 12, the mean LDL-C concentrations were reduced generally dose dependently by AMG 145 every 2 weeks (ranging from 41·8% to 66·1%; p<0·0001 for each dose vs placebo) and AMG 145 every 4 weeks (ranging from 41·8% to 50·3%; p<0·0001). No treatment-related serious adverse events occurred. The frequencies of treatment-related adverse events were similar in the AMG 145 and placebo groups (39 [8%] of 474 vs 11 [7%] of 155); none of these events were severe or life-threatening.InterpretationThe results suggest that PCSK9 inhibition could be a new model in lipid management. Inhibition of PCSK9 warrants assessment in phase 3 clinical trials.FundingAmgen.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 380, Issue 9858, 8–14 December 2012, Pages 2007–2017
نویسندگان
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