Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-3 (GAUSS-3)
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
調査の概要
状態
条件
詳細な説明
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).
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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California
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Beverly Hills、California、アメリカ、90211
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Huntington Beach、California、アメリカ、92648
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Los Angeles、California、アメリカ、90048
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San Pedro、California、アメリカ、90732
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Georgia
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Atlanta、Georgia、アメリカ、30322
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Illinois
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Sterling、Illinois、アメリカ、61081
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Kansas
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Kansas City、Kansas、アメリカ、66160
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Maryland
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Baltimore、Maryland、アメリカ、21201
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Towson、Maryland、アメリカ、21204
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Michigan
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Ann Arbor、Michigan、アメリカ、48106
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Minnesota
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Rochester、Minnesota、アメリカ、55905
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Missouri
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Saint Louis、Missouri、アメリカ、63110
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New York
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New York、New York、アメリカ、10029
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North Carolina
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Durham、North Carolina、アメリカ、27710
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Ohio
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Cleveland、Ohio、アメリカ、44195
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Pennsylvania
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York、Pennsylvania、アメリカ、17405
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South Carolina
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Charleston、South Carolina、アメリカ、29425
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Texas
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Houston、Texas、アメリカ、77030
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Birmingham、イギリス、B15 2TH
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Glasgow、イギリス、G12 8TA
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Newcastle upon Tyne、イギリス、NE1 4LP
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Bologna、イタリア、40138
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Cagliari、イタリア、09134
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Cinisello Balsamo (MI)、イタリア、20092
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Ferrara、イタリア、44100
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Perugia、イタリア、06129
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Pisa、イタリア、56124
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Amsterdam、オランダ、1105 AZ
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Rotterdam、オランダ、3045 PM
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Zwijndrecht、オランダ、3331 LZ
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New South Wales
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Camperdown、New South Wales、オーストラリア、2015
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Queensland
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Woolloongabba、Queensland、オーストラリア、4102
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South Australia
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Ashford、South Australia、オーストラリア、5035
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Quebec、カナダ、G1V 4M6
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British Columbia
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Vancouver、British Columbia、カナダ、V5Z 1M9
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Ontario
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Hamilton、Ontario、カナダ、L8L 2X2
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London、Ontario、カナダ、N6A 4V2
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Peterborough、Ontario、カナダ、K9J 0B2
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Quebec
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Montreal、Quebec、カナダ、H2W 1R7
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St-Charles-Borromee、Quebec、カナダ、J6E 6J2
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Hradec Kralove、チェコ、500 05
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Praha 2、チェコ、128 08
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Praha 4、チェコ、140 21
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Aarhus N、デンマーク、8200
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Glostrup、デンマーク、2600
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Berlin、ドイツ、13353
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Köln、ドイツ、50937
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München、ドイツ、80638
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Christchurch、ニュージーランド、8011
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Oslo、ノルウェー、0373
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Ålesund、ノルウェー、6003
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Nantes Cedex 1、フランス、44093
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Paris Cedex 13、フランス、75651
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Vénissieux、フランス、69200
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Gauteng
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Johannesburg、Gauteng、南アフリカ、2157
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Midrand、Gauteng、南アフリカ、1685
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Western Cape
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Observatory、Western Cape、南アフリカ、7925
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Parow、Western Cape、南アフリカ、7505
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
他の：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.
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Atorvastatin was supplied as over-encapsulated 20 mg tablets
他の名前：
Placebo matching to atorvastatin supplied as over-encapsulated tablets
|
|
他の：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.
|
Atorvastatin was supplied as over-encapsulated 20 mg tablets
他の名前：
Placebo matching to atorvastatin supplied as over-encapsulated tablets
|
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アクティブコンパレータ：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.
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Ezetimibe was supplied as 10 mg tablets, over-encapsulated for blinding.
他の名前：
Placebo matching to evolocumab supplied as single-use prefilled autoinjector/pen(s)
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実験的：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.
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Placebo matching to Ezetimibe supplied as over-encapsulated tablets.
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
他の名前：
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実験的：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.
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Evolocumab supplied as single-use prefilled autoinjector/pen(s)
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
時間枠：Baseline and weeks 22 and 24
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Baseline and weeks 22 and 24
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Percent Change From Baseline in LDL-C at Week 24
時間枠：Baseline and week 24
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Baseline and week 24
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
時間枠：Baselie and weeks 22 and 24
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Baselie and weeks 22 and 24
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Change From Baseline in LDL-C at Week 24
時間枠：Baseline and week 24
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Baseline and week 24
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Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL
時間枠：Weeks 22 and 24
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Weeks 22 and 24
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Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL
時間枠：Week 24
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Week 24
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Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24
時間枠：Baseline and weeks 22 and 24
|
Baseline and weeks 22 and 24
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Percent Change From Baseline in Total Cholesterol at Week 24
時間枠：Baseline and week 24
|
Baseline and week 24
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Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 22 and 24
時間枠：Baseline and weeks 22 and 24
|
Baseline and weeks 22 and 24
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Percent Change From Baseline in Non-HDL-C at Week 24
時間枠：Baseline and week 24
|
Baseline and week 24
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Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24
時間枠：Baseline and weeks 22 and 24
|
Baseline and weeks 22 and 24
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Percent Change From Baseline in Apolipoprotein B at Week 24
時間枠：Baseline and week 24
|
Baseline and week 24
|
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Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 22 and 24
時間枠：Baseline and weeks 22 and 24
|
Baseline and weeks 22 and 24
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Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 24
時間枠：Baseline and week 24
|
Baseline and week 24
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Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 22 and 24
時間枠：Baseline and Weeks 22 and 24
|
Baseline and Weeks 22 and 24
|
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Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24
時間枠：Baseline and week 24
|
Baseline and week 24
|
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Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24
時間枠：Baseline and Weeks 22 and 24
|
Baseline and Weeks 22 and 24
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Percent Change From Baseline in Lipoprotein(a) at Week 24
時間枠：Baseline and week 24
|
Baseline and week 24
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Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24
時間枠：Baseline and weeks 22 and 24
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Baseline and weeks 22 and 24
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Percent Change From Baseline in Triglycerides at Week 24
時間枠：Baseline and week 24
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Baseline and week 24
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Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24
時間枠：Baseline and weeks 22 and 24
|
Baseline and weeks 22 and 24
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Percent Change From Baseline in HDL-C at Week 24
時間枠：Baseline and week 24
|
Baseline and week 24
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Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 22 and 24
時間枠：Baseline and weeks 22 and 24
|
Baseline and weeks 22 and 24
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Percent Change From Baseline in VLDL-C at Week 24
時間枠：Baseline and week 24
|
Baseline and week 24
|
協力者と研究者
スポンサー
出版物と役立つリンク
一般刊行物
- Cho L, Dent R, Stroes ESG, Stein EA, Sullivan D, Ruzza A, Flower A, Somaratne R, Rosenson RS. Persistent Safety and Efficacy of Evolocumab in Patients with Statin Intolerance: a Subset Analysis of the OSLER Open-Label Extension Studies. Cardiovasc Drugs Ther. 2018 Aug;32(4):365-372. doi: 10.1007/s10557-018-6817-7.
- Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.
- Nissen SE, Stroes E, Dent-Acosta RE, Rosenson RS, Lehman SJ, Sattar N, Preiss D, Bruckert E, Ceska R, Lepor N, Ballantyne CM, Gouni-Berthold I, Elliott M, Brennan DM, Wasserman SM, Somaratne R, Scott R, Stein EA; GAUSS-3 Investigators. Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial. JAMA. 2016 Apr 19;315(15):1580-90. doi: 10.1001/jama.2016.3608.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 20120332
- 2013-000935-29 (EudraCT番号)
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。