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

1. november 2018 oppdatert av: 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).

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert 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).

Studietype

Intervensjonell

Registrering (Faktiske)

511

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2015
        • Research Site
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
        • Research Site
    • South Australia
      • Ashford, South Australia, Australia, 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
  • Forente stater
    • California
      • Beverly Hills, California, Forente stater, 90211
        • Research Site
      • Huntington Beach, California, Forente stater, 92648
        • Research Site
      • Los Angeles, California, Forente stater, 90048
        • Research Site
      • San Pedro, California, Forente stater, 90732
        • Research Site
    • Georgia
      • Atlanta, Georgia, Forente stater, 30322
        • Research Site
    • Illinois
      • Sterling, Illinois, Forente stater, 61081
        • Research Site
    • Kansas
      • Kansas City, Kansas, Forente stater, 66160
        • Research Site
    • Maryland
      • Baltimore, Maryland, Forente stater, 21201
        • Research Site
      • Towson, Maryland, Forente stater, 21204
        • Research Site
    • Michigan
      • Ann Arbor, Michigan, Forente stater, 48106
        • Research Site
    • Minnesota
      • Rochester, Minnesota, Forente stater, 55905
        • Research Site
    • Missouri
      • Saint Louis, Missouri, Forente stater, 63110
        • Research Site
    • New York
      • New York, New York, Forente stater, 10029
        • Research Site
    • North Carolina
      • Durham, North Carolina, Forente stater, 27710
        • Research Site
    • Ohio
      • Cleveland, Ohio, Forente stater, 44195
        • Research Site
    • Pennsylvania
      • York, Pennsylvania, Forente stater, 17405
        • Research Site
    • South Carolina
      • Charleston, South Carolina, Forente stater, 29425
        • Research Site
    • Texas
      • Houston, Texas, Forente stater, 77030
        • Research Site
  • Frankrike
      • Nantes Cedex 1, Frankrike, 44093
        • Research Site
      • Paris Cedex 13, Frankrike, 75651
        • Research Site
      • Vénissieux, Frankrike, 69200
        • Research Site
  • Italia
      • Bologna, Italia, 40138
        • Research Site
      • Cagliari, Italia, 09134
        • Research Site
      • Cinisello Balsamo (MI), Italia, 20092
        • Research Site
      • Ferrara, Italia, 44100
        • Research Site
      • Perugia, Italia, 06129
        • Research Site
      • Pisa, Italia, 56124
        • Research Site
  • Nederland
      • Amsterdam, Nederland, 1105 AZ
        • Research Site
      • Rotterdam, Nederland, 3045 PM
        • Research Site
      • Zwijndrecht, Nederland, 3331 LZ
        • Research Site
  • New Zealand
      • Christchurch, New Zealand, 8011
        • Research Site
  • Norge
      • Oslo, Norge, 0373
        • Research Site
      • Ålesund, Norge, 6003
        • Research Site
  • Storbritannia
      • Birmingham, Storbritannia, B15 2TH
        • Research Site
      • Glasgow, Storbritannia, G12 8TA
        • Research Site
      • Newcastle upon Tyne, Storbritannia, NE1 4LP
        • Research Site
  • Sør-Afrika
    • Gauteng
      • Johannesburg, Gauteng, Sør-Afrika, 2157
        • Research Site
      • Midrand, Gauteng, Sør-Afrika, 1685
        • Research Site
    • Western Cape
      • Observatory, Western Cape, Sør-Afrika, 7925
        • Research Site
      • Parow, Western Cape, Sør-Afrika, 7505
        • Research Site
  • Tsjekkia
      • Hradec Kralove, Tsjekkia, 500 05
        • Research Site
      • Praha 2, Tsjekkia, 128 08
        • Research Site
      • Praha 4, Tsjekkia, 140 21
        • Research Site
  • Tyskland
      • Berlin, Tyskland, 13353
        • Research Site
      • Köln, Tyskland, 50937
        • Research Site
      • München, Tyskland, 80638
        • Research Site

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 80 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Annen: 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.
Legemiddel: Atorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets
Andre navn:
  • Lipitor
Legemiddel: Placebo to Atorvastatin
Placebo matching to atorvastatin supplied as over-encapsulated tablets
Annen: 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.
Legemiddel: Atorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets
Andre navn:
  • Lipitor
Legemiddel: 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.
Legemiddel: Ezetimibe
Ezetimibe was supplied as 10 mg tablets, over-encapsulated for blinding.
Andre navn:
  • Zetia
Annen: Placebo to Evolocumab
Placebo matching to evolocumab supplied as single-use prefilled autoinjector/pen(s)
Eksperimentell: 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.
Annen: Placebo to Ezetimibe
Placebo matching to Ezetimibe supplied as over-encapsulated tablets.
Legemiddel: Evolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
Andre navn:
  • Repatha
Eksperimentell: 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.
Legemiddel: Evolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
Andre navn:
  • Repatha

Hva måler studien?

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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Amgen

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

10. desember 2013

Primær fullføring (Faktiske)

10. november 2015

Studiet fullført (Faktiske)

21. november 2017

Datoer for studieregistrering

Først innsendt

8. november 2013

Først innsendt som oppfylte QC-kriteriene

8. november 2013

Først lagt ut (Anslag)

14. november 2013

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

29. november 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

1. november 2018

Sist bekreftet

1. november 2018

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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