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

1 novembre 2018 aggiornato da: 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).

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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).

Tipo di studio

Interventistico

Iscrizione (Effettivo)

511

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • 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
  • Cechia
      • Hradec Kralove, Cechia, 500 05
        • Research Site
      • Praha 2, Cechia, 128 08
        • Research Site
      • Praha 4, Cechia, 140 21
        • Research Site
  • Danimarca
      • Aarhus N, Danimarca, 8200
        • Research Site
      • Glostrup, Danimarca, 2600
        • Research Site
  • Francia
      • Nantes Cedex 1, Francia, 44093
        • Research Site
      • Paris Cedex 13, Francia, 75651
        • Research Site
      • Vénissieux, Francia, 69200
        • Research Site
  • Germania
      • Berlin, Germania, 13353
        • Research Site
      • Köln, Germania, 50937
        • Research Site
      • München, Germania, 80638
        • 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
  • Norvegia
      • Oslo, Norvegia, 0373
        • Research Site
      • Ålesund, Norvegia, 6003
        • Research Site
  • Nuova Zelanda
      • Christchurch, Nuova Zelanda, 8011
        • Research Site
  • Olanda
      • Amsterdam, Olanda, 1105 AZ
        • Research Site
      • Rotterdam, Olanda, 3045 PM
        • Research Site
      • Zwijndrecht, Olanda, 3331 LZ
        • Research Site
  • Regno Unito
      • Birmingham, Regno Unito, B15 2TH
        • Research Site
      • Glasgow, Regno Unito, G12 8TA
        • Research Site
      • Newcastle upon Tyne, Regno Unito, NE1 4LP
        • Research Site
  • Stati Uniti
    • California
      • Beverly Hills, California, Stati Uniti, 90211
        • Research Site
      • Huntington Beach, California, Stati Uniti, 92648
        • Research Site
      • Los Angeles, California, Stati Uniti, 90048
        • Research Site
      • San Pedro, California, Stati Uniti, 90732
        • Research Site
    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30322
        • Research Site
    • Illinois
      • Sterling, Illinois, Stati Uniti, 61081
        • Research Site
    • Kansas
      • Kansas City, Kansas, Stati Uniti, 66160
        • Research Site
    • Maryland
      • Baltimore, Maryland, Stati Uniti, 21201
        • Research Site
      • Towson, Maryland, Stati Uniti, 21204
        • Research Site
    • Michigan
      • Ann Arbor, Michigan, Stati Uniti, 48106
        • Research Site
    • Minnesota
      • Rochester, Minnesota, Stati Uniti, 55905
        • Research Site
    • Missouri
      • Saint Louis, Missouri, Stati Uniti, 63110
        • Research Site
    • New York
      • New York, New York, Stati Uniti, 10029
        • Research Site
    • North Carolina
      • Durham, North Carolina, Stati Uniti, 27710
        • Research Site
    • Ohio
      • Cleveland, Ohio, Stati Uniti, 44195
        • Research Site
    • Pennsylvania
      • York, Pennsylvania, Stati Uniti, 17405
        • Research Site
    • South Carolina
      • Charleston, South Carolina, Stati Uniti, 29425
        • Research Site
    • Texas
      • Houston, Texas, Stati Uniti, 77030
        • Research Site
  • Sud Africa
    • Gauteng
      • Johannesburg, Gauteng, Sud Africa, 2157
        • Research Site
      • Midrand, Gauteng, Sud Africa, 1685
        • Research Site
    • Western Cape
      • Observatory, Western Cape, Sud Africa, 7925
        • Research Site
      • Parow, Western Cape, Sud Africa, 7505
        • Research Site

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Altro: 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.
Droga: Atorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets
Altri nomi:
  • Lipitore
Droga: Placebo to Atorvastatin
Placebo matching to atorvastatin supplied as over-encapsulated tablets
Altro: 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.
Droga: Atorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets
Altri nomi:
  • Lipitore
Droga: Placebo to Atorvastatin
Placebo matching to atorvastatin supplied as over-encapsulated tablets
Comparatore attivo: 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.
Droga: Ezetimibe
Ezetimibe was supplied as 10 mg tablets, over-encapsulated for blinding.
Altri nomi:
  • Zezia
Altro: Placebo to Evolocumab
Placebo matching to evolocumab supplied as single-use prefilled autoinjector/pen(s)
Sperimentale: 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.
Altro: Placebo to Ezetimibe
Placebo matching to Ezetimibe supplied as over-encapsulated tablets.
Droga: Evolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
Altri nomi:
  • Repatha
Sperimentale: 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.
Droga: Evolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
Altri nomi:
  • Repatha

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
Lasso di tempo: Baseline and weeks 22 and 24
Baseline and weeks 22 and 24
Percent Change From Baseline in LDL-C at Week 24
Lasso di tempo: Baseline and week 24
Baseline and week 24

Misure di risultato secondarie

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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Amgen

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

10 dicembre 2013

Completamento primario (Effettivo)

10 novembre 2015

Completamento dello studio (Effettivo)

21 novembre 2017

Date di iscrizione allo studio

Primo inviato

8 novembre 2013

Primo inviato che soddisfa i criteri di controllo qualità

8 novembre 2013

Primo Inserito (Stima)

14 novembre 2013

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

29 novembre 2018

Ultimo aggiornamento inviato che soddisfa i criteri QC

1 novembre 2018

Ultimo verificato

1 novembre 2018

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

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

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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Condizioni

Malattie rare

Interventi farmacologici

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Sponsor / Collaboratori

Sedi

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