Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2 (GAUSS-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01763905
First received: January 7, 2013
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

The primary hypothesis is that both dosing regimens of Evolocumab (AMG 145) will be well tolerated and will result in greater reduction of Low Density Lipoprotein (LDL-C), than ezetimibe in hypercholesterolemic subjects unable to tolerate an effective dose of a statin.


Condition Intervention Phase
Hyperlipidemia
Biological: Evolocumab (AMG 145)
Other: Placebo (administered subcutaneously)
Drug: Ezetimibe
Other: Placebo (administered orally)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of Evolocumab (AMG 145), Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Mean percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in low density lipoprotein-cholesterol

  • Percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in low density lipoprotein-cholesterol


Secondary Outcome Measures:
  • Mean change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean change from baseline in low density lipoprotein-cholesterol

  • Change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Change from baseline in low density lipoprotein-cholesterol

  • Mean low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])

  • Low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])

  • Mean percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in non-high density lipoprotein-cholesterol

  • Percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in non-high density lipoprotein-cholesterol

  • Mean percent change from baseline in apolipoprotein B [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in apolipoprotein B

  • Percent change from baseline in apolipoprotein B [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in apolipoprotein B

  • Mean percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio

  • Percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio

  • Mean percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio

  • Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio

  • Mean percent change from baseline in lipoprotein (a) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in lipoprotein (a)

  • Percent change from baseline in lipoprotein (a) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in lipoprotein (a)

  • Mean percent change from baseline in triglycerides [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in triglycerides

  • Percent change from baseline in triglycerides [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in triglycerides

  • Mean percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in high density lipoprotein-cholesterol

  • Percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in high density lipoprotein-cholesterol

  • Mean percent change from baseline in very low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in very low density lipoprotein-cholesterol

  • Percent change from baseline in very low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in very low density lipoprotein-cholesterol


Enrollment: 307
Study Start Date: January 2013
Study Completion Date: January 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Dose 1 of subcutaneous Evolocumab(AMG 145) every 2 weeks and placebo orally/daily
Biological: Evolocumab (AMG 145)
Subjects will receive Evolocumab (AMG 145) every 2 weeks or monthly
Other: Placebo (administered orally)
Subject will receive Placebo daily
Experimental: Arm 2
Dose 2 of subcutaneous Evolocumab(AMG 145) monthly and placebo orally/daily
Biological: Evolocumab (AMG 145)
Subjects will receive Evolocumab (AMG 145) every 2 weeks or monthly
Other: Placebo (administered orally)
Subject will receive Placebo daily
Active Comparator: Arm 3
Dose 3 of subcutaneous placebo every 2 weeks and Ezetimibe orally/daily
Other: Placebo (administered subcutaneously)
Subjects will receive Placebo every 2 weeks or monthly. All patients at screening will participate in the placebo run-in.
Drug: Ezetimibe
Subjects will receive Ezetimibe daily
Active Comparator: Arm 4
Dose 4 of subcutaneous placebo monthly and Ezetimibe orally/daily
Other: Placebo (administered subcutaneously)
Subjects will receive Placebo every 2 weeks or monthly. All patients at screening will participate in the placebo run-in.
Drug: Ezetimibe
Subjects will receive Ezetimibe daily

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female ≥ 18 to ≤ 80 years of age
  • Not on a statin or on a low dose statin with stable dose for at least 4 weeks
  • History of intolerance to at least 2 statins
  • Subject not at LDL-C goal
  • Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks.
  • Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria:

  • NYHA III or IV heart failure
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled hypertension
  • Type 1 diabetes, poorly controlled type 2 diabetes
  • Uncontrolled hypothyroidism or hyperthyroidism
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763905

  Hide Study Locations
Locations
United States, California
Research Site
Carmichael, California, United States, 95608
Research Site
Los Angeles, California, United States, 90048
Research Site
Mission Viejo, California, United States, 92691
Research Site
Thousand Oaks, California, United States, 91360
United States, Georgia
Research Site
Atlanta, Georgia, United States, 30338
Research Site
Atlanta, Georgia, United States, 30342
Research Site
Savannah, Georgia, United States, 31406
United States, Maine
Research Site
Auburn, Maine, United States, 04210
United States, Michigan
Research Site
Traverse City, Michigan, United States, 49684
United States, Missouri
Research Site
St. Louis, Missouri, United States, 63110
United States, Nevada
Research Site
Henderson, Nevada, United States, 89052
Research Site
Las Vegas, Nevada, United States, 89117
Research Site
Las Vegas, Nevada, United States, 89148
United States, New York
Research Site
New York, New York, United States, 10029
United States, North Carolina
Research Site
Raleigh, North Carolina, United States, 27609
United States, Ohio
Research Site
Akron, Ohio, United States, 44311
Research Site
Cincinnati, Ohio, United States, 45212
Research Site
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Research Site
Norman, Oklahoma, United States, 73069
United States, Texas
Research Site
Houston, Texas, United States, 77030
Australia, New South Wales
Research Site
Camperdown, New South Wales, Australia, 2015
Australia, Queensland
Research Site
Milton, Queensland, Australia, 4064
Australia, Victoria
Research Site
Melbourne, Victoria, Australia, 3004
Australia, Western Australia
Research Site
Perth, Western Australia, Australia, 6000
Belgium
Research Site
Brussels, Belgium, 1200
Research Site
Gent, Belgium, 9000
Research Site
La Louvière, Belgium, 7100
Canada, Ontario
Research Site
Newmarket, Ontario, Canada, L3Y 5G8
Canada, Quebec
Research Site
Lachine, Quebec, Canada, H8S 2E4
Research Site
Pointe-Claire, Quebec, Canada, H9R 3J1
Denmark
Research Site
Aalborg, Denmark, 9000
Research Site
Ballerup, Denmark, 2750
Research Site
Vejle, Denmark, 7100
France
Research Site
Lille Cedex, France, 59037
Research Site
Paris Cedex 13, France, 75651
Research Site
Vénissieux, France, 69200
Germany
Research Site
Bad Krozingen, Germany, 79189
Research Site
Dresden, Germany, 01307
Research Site
Heppenheim, Germany, 64646
Hong Kong
Research Site
Hong Kong, Hong Kong
Research Site
New Territories, Hong Kong
Netherlands
Research Site
Alkmaar, Netherlands, 1815 JD
Research Site
Amsterdam, Netherlands, 1105 AZ
Research Site
Groningen, Netherlands, 9713 GZ
Poland
Research Site
Lodz, Poland, 90-368
Research Site
Warszawa, Poland, 04-730
South Africa
Research Site
Midrand, Gauteng, South Africa, 1685
Research Site
Observatory, Western Cape, South Africa, 7925
Research Site
Somerset West, Western Cape, South Africa, 7130
Spain
Research Site
Cordoba, Andalucía, Spain, 14004
Research Site
Zaragoza, Aragón, Spain, 50009
Research Site
Reus, Cataluña, Spain, 43204
Switzerland
Research Site
Lugano, Switzerland, 6900
Research Site
Reinach, Switzerland, 4153
United Kingdom
Research Site
Liverpool, United Kingdom, L22 0LG
Research Site
London, United Kingdom, NW3 2QG
Research Site
Telford, United Kingdom, TF1 6TF
Research Site
West Bromwich, United Kingdom, B71 4HJ
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01763905     History of Changes
Other Study ID Numbers: 20110116
Study First Received: January 7, 2013
Last Updated: May 29, 2014
Health Authority: Hong Kong: Department of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Australia: Department of Health and Ageing Therapeutic Goods Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Spain: Agencia Española de Medicamentos y Productos Sanitarios
South Africa: Medicines Control Council
Switzerland: Swissmedic
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Health and Medicines Authority
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by Amgen:
High Cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Additional relevant MeSH terms:
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Ezetimibe
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014