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Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-3 (GAUSS-3)

2018年11月1日 更新者：Amgen

A Double-blind, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Evolocumab, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor Due to Muscle Related Side Effects

The primary objective of this study was to evaluate the effect of 24 weeks of evolocumab administered subcutaneously (SC) every month, compared with ezetimibe, on low-density lipoprotein cholesterol (LDL-C) levels in adults with high cholesterol who are unable to tolerate an effective dose of a statin due to muscle-related side effects (MRSE).

研究概览

地位

完全的

条件

干预/治疗

详细说明

The study is divided into 3 parts (A, B, C). After an initial 4-week washout period in which any statins, ezetimibe, or other lipid-lowering agents were discontinued, participants were enrolled in phase A, a double-blind, placebo-controlled crossover procedure to rechallenge patients with atorvastatin. Patients were randomly assigned in a 1:1 ratio to receive either atorvastatin (20 mg daily) or matching placebo for the first 10 weeks (period 1), then underwent a 2-week washout period, followed by crossover to the alternate therapy for a second 10-week period (period 2). Patients who experienced intolerable muscle symptoms during the first period did not complete the full 10 weeks of exposure but entered a 2-week washout period before proceeding to period 2.

Participants who did not develop muscle-related side effects were removed from the study, as were patients who reported muscle-related side effects during a placebo period.

After completion of phase A, patients who experienced muscle-related adverse effects while taking atorvastatin but not placebo were eligible for phase B, a 24-week, double-blind randomization to ezetimibe or evolocumab using a double-dummy design in which patients received either injectable placebo and oral ezetimibe or injectable evolocumab and oral placebo. A patient could proceed directly to phase B if they had a documented history of creatine kinase (CK) elevation more than 10 times the upper limit of normal accompanied by muscle symptoms while taking statin therapy, with documented resolution of both CK elevation and symptoms upon discontinuation of statin therapy.

These study procedures were designed to ensure that only patients with reproducible statin-associated muscle symptoms entered phase B of the study. For phase B, participants were randomized 2:1 to receive subcutaneously administered evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). Randomization in part B was stratified by screening LDL-C level (< 180 mg/dL [4.66 mmol/L] vs. ≥ 180 mg/dL) at study baseline.

Participants who completed phase B and did not discontinue SC investigational product for any reason, including an adverse event, were eligible to proceed to the 2-year open-label extension phase C to evaluate the long-term safety and efficacy of evolocumab in statin-intolerant patients. Participants in phase C were allowed to choose quarterly between evolocumab 420 mg SC QM or evolocumab 140 mg SC every 2 weeks (Q2W).

研究类型

介入性

注册 (实际的)

511

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 丹麦
      • Aarhus N、丹麦、8200
        • Research Site
      • Glostrup、丹麦、2600
        • Research Site
  • 加拿大
      • Quebec、加拿大、G1V 4M6
        • Research Site
    • British Columbia
      • Vancouver、British Columbia、加拿大、V5Z 1M9
        • Research Site
    • Ontario
      • Hamilton、Ontario、加拿大、L8L 2X2
        • Research Site
      • London、Ontario、加拿大、N6A 4V2
        • Research Site
      • Peterborough、Ontario、加拿大、K9J 0B2
        • Research Site
    • Quebec
      • Montreal、Quebec、加拿大、H2W 1R7
        • Research Site
      • St-Charles-Borromee、Quebec、加拿大、J6E 6J2
        • Research Site
  • 南非
    • Gauteng
      • Johannesburg、Gauteng、南非、2157
        • Research Site
      • Midrand、Gauteng、南非、1685
        • Research Site
    • Western Cape
      • Observatory、Western Cape、南非、7925
        • Research Site
      • Parow、Western Cape、南非、7505
        • Research Site
  • 德国
      • Berlin、德国、13353
        • Research Site
      • Köln、德国、50937
        • Research Site
      • München、德国、80638
        • Research Site
  • 意大利
      • Bologna、意大利、40138
        • Research Site
      • Cagliari、意大利、09134
        • Research Site
      • Cinisello Balsamo (MI)、意大利、20092
        • Research Site
      • Ferrara、意大利、44100
        • Research Site
      • Perugia、意大利、06129
        • Research Site
      • Pisa、意大利、56124
        • Research Site
  • 挪威
      • Oslo、挪威、0373
        • Research Site
      • Ålesund、挪威、6003
        • Research Site
  • 捷克语
      • Hradec Kralove、捷克语、500 05
        • Research Site
      • Praha 2、捷克语、128 08
        • Research Site
      • Praha 4、捷克语、140 21
        • Research Site
  • 新西兰
      • Christchurch、新西兰、8011
        • Research Site
  • 法国
      • Nantes Cedex 1、法国、44093
        • Research Site
      • Paris Cedex 13、法国、75651
        • Research Site
      • Vénissieux、法国、69200
        • Research Site
  • 澳大利亚
    • New South Wales
      • Camperdown、New South Wales、澳大利亚、2015
        • Research Site
    • Queensland
      • Woolloongabba、Queensland、澳大利亚、4102
        • Research Site
    • South Australia
      • Ashford、South Australia、澳大利亚、5035
        • Research Site
  • 美国
    • California
      • Beverly Hills、California、美国、90211
        • Research Site
      • Huntington Beach、California、美国、92648
        • Research Site
      • Los Angeles、California、美国、90048
        • Research Site
      • San Pedro、California、美国、90732
        • Research Site
    • Georgia
      • Atlanta、Georgia、美国、30322
        • Research Site
    • Illinois
      • Sterling、Illinois、美国、61081
        • Research Site
    • Kansas
      • Kansas City、Kansas、美国、66160
        • Research Site
    • Maryland
      • Baltimore、Maryland、美国、21201
        • Research Site
      • Towson、Maryland、美国、21204
        • Research Site
    • Michigan
      • Ann Arbor、Michigan、美国、48106
        • Research Site
    • Minnesota
      • Rochester、Minnesota、美国、55905
        • Research Site
    • Missouri
      • Saint Louis、Missouri、美国、63110
        • Research Site
    • New York
      • New York、New York、美国、10029
        • Research Site
    • North Carolina
      • Durham、North Carolina、美国、27710
        • Research Site
    • Ohio
      • Cleveland、Ohio、美国、44195
        • Research Site
    • Pennsylvania
      • York、Pennsylvania、美国、17405
        • Research Site
    • South Carolina
      • Charleston、South Carolina、美国、29425
        • Research Site
    • Texas
      • Houston、Texas、美国、77030
        • Research Site
  • 英国
      • Birmingham、英国、B15 2TH
        • Research Site
      • Glasgow、英国、G12 8TA
        • Research Site
      • Newcastle upon Tyne、英国、NE1 4LP
        • Research Site
  • 荷兰
      • Amsterdam、荷兰、1105 AZ
        • Research Site
      • Rotterdam、荷兰、3045 PM
        • Research Site
      • Zwijndrecht、荷兰、3331 LZ
        • Research Site

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 80年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Male or female ≥ 18 to ≤ 80 years of age
  • Subject not at LDL-C goal
  • History of statin intolerance
  • Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks
  • Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria:

  • New York Heart Association (NYHA) III or IV heart failure
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled hypertension
  • Type 1 diabetes
  • Poorly controlled type 2 diabetes
  • Uncontrolled hypothyroidism or hyperthyroidism

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
其他：Part A: Atorvastatin 20 mg => Placebo
Participants received atorvastatin 20 mg orally for 10 weeks (period 1) followed by placebo orally for 10 weeks (period 2), separated by a 2-week washout period.
药品：Atorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets
其他名称：
  • 立普妥
药品：Placebo to Atorvastatin
Placebo matching to atorvastatin supplied as over-encapsulated tablets
其他：Part A: Placebo => Atorvastatin 20 mg
Participants received placebo orally for 10 weeks (period 1) followed by atorvastatin 20 mg orally for 10 weeks (period 2), separated by a 2-week washout period.
药品：Atorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets
其他名称：
  • 立普妥
药品：Placebo to Atorvastatin
Placebo matching to atorvastatin supplied as over-encapsulated tablets
有源比较器：Part B: Ezetimibe
Participants received 10 mg ezetimibe orally only a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks.
药品：Ezetimibe
Ezetimibe was supplied as 10 mg tablets, over-encapsulated for blinding.
其他名称：
  • 泽蒂亚
其他：Placebo to Evolocumab
Placebo matching to evolocumab supplied as single-use prefilled autoinjector/pen(s)
实验性的：Part B: Evolocumab
Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks.
其他：Placebo to Ezetimibe
Placebo matching to Ezetimibe supplied as over-encapsulated tablets.
药品：Evolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
其他名称：
  • 修复
实验性的：Part C: Open-label Evolocumab
Participants who completed part B and were eligible to proceed to open-label extension part C and could choose quarterly between evolocumab 420 mg once a month or evolocumab 140 mg every 2 weeks for up to 2 years.
药品：Evolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
其他名称：
  • 修复

研究衡量的是什么？

主要结果指标

结果测量
大体时间
Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
大体时间：Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in LDL-C at Week 24
大体时间：Baseline and week 24
Baseline and week 24

次要结果测量

结果测量
大体时间
Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
大体时间：Baselie and weeks 22 and 24
Baselie and weeks 22 and 24
Change From Baseline in LDL-C at Week 24
大体时间：Baseline and week 24
Baseline and week 24
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL
大体时间：Weeks 22 and 24
Weeks 22 and 24
Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL
大体时间：Week 24
Week 24
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24
大体时间：Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in Total Cholesterol at Week 24
大体时间：Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 22 and 24
大体时间：Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in Non-HDL-C at Week 24
大体时间：Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24
大体时间：Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in Apolipoprotein B at Week 24
大体时间：Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 22 and 24
大体时间：Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 24
大体时间：Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 22 and 24
大体时间：Baseline and Weeks 22 and 24
Baseline and Weeks 22 and 24
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24
大体时间：Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24
大体时间：Baseline and Weeks 22 and 24
Baseline and Weeks 22 and 24
Percent Change From Baseline in Lipoprotein(a) at Week 24
大体时间：Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24
大体时间：Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in Triglycerides at Week 24
大体时间：Baseline and week 24
Baseline and week 24
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24
大体时间：Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in HDL-C at Week 24
大体时间：Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 22 and 24
大体时间：Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in VLDL-C at Week 24
大体时间：Baseline and week 24
Baseline and week 24

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Amgen

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2013年12月10日

初级完成 (实际的)

2015年11月10日

研究完成 (实际的)

2017年11月21日

研究注册日期

首次提交

2013年11月8日

首先提交符合 QC 标准的

2013年11月8日

首次发布 (估计)

2013年11月14日

研究记录更新

最后更新发布 (实际的)

2018年11月29日

上次提交的符合 QC 标准的更新

2018年11月1日

最后验证

2018年11月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 20120332
  • 2013-000935-29 (EudraCT编号)

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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