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

1. november 2018 opdateret af: 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).

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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).

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

511

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 80 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Andet: 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.
Medicin: Atorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets
Andre navne:
  • Lipitor
Medicin: Placebo to Atorvastatin
Placebo matching to atorvastatin supplied as over-encapsulated tablets
Andet: 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.
Medicin: Atorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets
Andre navne:
  • Lipitor
Medicin: Placebo to Atorvastatin
Placebo matching to atorvastatin supplied as over-encapsulated tablets
Aktiv komparator: 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.
Medicin: Ezetimibe
Ezetimibe was supplied as 10 mg tablets, over-encapsulated for blinding.
Andre navne:
  • Zetia
Andet: Placebo to Evolocumab
Placebo matching to evolocumab supplied as single-use prefilled autoinjector/pen(s)
Eksperimentel: 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.
Andet: Placebo to Ezetimibe
Placebo matching to Ezetimibe supplied as over-encapsulated tablets.
Medicin: Evolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
Andre navne:
  • Repatha
Eksperimentel: 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.
Medicin: Evolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
Andre navne:
  • Repatha

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
Tidsramme: Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in LDL-C at Week 24
Tidsramme: Baseline and week 24
Baseline and week 24

Sekundære resultatmål

Resultatmål
Tidsramme
Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
Tidsramme: Baselie and weeks 22 and 24
Baselie and weeks 22 and 24
Change From Baseline in LDL-C at Week 24
Tidsramme: 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
Tidsramme: Weeks 22 and 24
Weeks 22 and 24
Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL
Tidsramme: Week 24
Week 24
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24
Tidsramme: Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in Total Cholesterol at Week 24
Tidsramme: 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
Tidsramme: Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in Non-HDL-C at Week 24
Tidsramme: Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24
Tidsramme: Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in Apolipoprotein B at Week 24
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24
Tidsramme: Baseline and Weeks 22 and 24
Baseline and Weeks 22 and 24
Percent Change From Baseline in Lipoprotein(a) at Week 24
Tidsramme: Baseline and week 24
Baseline and week 24
Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24
Tidsramme: Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in Triglycerides at Week 24
Tidsramme: Baseline and week 24
Baseline and week 24
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24
Tidsramme: Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in HDL-C at Week 24
Tidsramme: 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
Tidsramme: Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in VLDL-C at Week 24
Tidsramme: Baseline and week 24
Baseline and week 24

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Amgen

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

10. december 2013

Primær færdiggørelse (Faktiske)

10. november 2015

Studieafslutning (Faktiske)

21. november 2017

Datoer for studieregistrering

Først indsendt

8. november 2013

Først indsendt, der opfyldte QC-kriterier

8. november 2013

Først opslået (Skøn)

14. november 2013

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

29. november 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

1. november 2018

Sidst verificeret

1. november 2018

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Atorvastatin

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Sponsorer og samarbejdspartnere

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Betingelser

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Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

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