Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01984424
First received: November 8, 2013
Last updated: December 15, 2014
Last verified: December 2014
  Purpose

The study is divided into 3 parts (A, B, C). Part A is a double-blind, placebo-controlled, two-period cross-over rechallenge of atorvastatin 20 mg. Part B is a 24-week double-blind, double-dummy comparison of evolocumab and ezetimibe. Part C is a 2-year open-label evolocumab extension. The primary hypothesis is that evolocumab will be well tolerated and will result in greater reduction of LDL-C than ezetimibe, defined by the mean percent change from baseline at Weeks 22 and 24 of Part B and percent change from baseline at Week 24 of Part B, in statin-intolerant hypercholesterolemic subjects.


Condition Intervention Phase
Hyperlipidemia
Drug: Part A, Atorvastatin
Other: Part A, Placebo (administered orally)
Drug: Part B, Evolocumab
Other: Part B, Placebo (administered orally)
Drug: Part B, Ezetimibe
Other: Part B, Placebo (administered subcutaneously)
Drug: Part C, Evolocumab
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 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

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: 22 and 24 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: 24 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: 22 and 24 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: 24 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: 22 and 24 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: 24 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 total cholesterol [ Time Frame: 22 and 24 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in total cholesterol

  • Percent change from baseline in total cholesterol [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in total cholesterol

  • Mean percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 22 and 24 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: 24 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: 22 and 24 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in apolipoprotein B

  • Percent change from baseline in apolipoprotein B [ Time Frame: 24 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: 22 and 24 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: 24 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: 22 and 24 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: 24 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: 22 and 24 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in lipoprotein (a)

  • Percent change from baseline in lipoprotein (a) [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in lipoprotein (a)

  • Mean percent change from baseline in triglycerides [ Time Frame: 22 and 24 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in triglycerides

  • Percent change from baseline in triglycerides [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in triglycerides

  • Mean percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 22 and 24 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: 24 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: 22 and 24 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: 24 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in very low density lipoprotein-cholesterol


Enrollment: 519
Study Start Date: December 2013
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A (two-period cross-over), Arm 1
Atorvastatin
Drug: Part A, Atorvastatin
Subjects will receive atorvastatin daily
Other: Part A, Placebo (administered orally)
Subjects will receive oral placebo daily
Placebo Comparator: Part A (two-period cross-over), Arm 2
Placebo
Drug: Part A, Atorvastatin
Subjects will receive atorvastatin daily
Other: Part A, Placebo (administered orally)
Subjects will receive oral placebo daily
Experimental: Part B, Arm 1
Evolocumab
Drug: Part B, Evolocumab
Subjects will receive subcutaneous evolocumab every month
Other: Part B, Placebo (administered orally)
Subjects will receive oral placebo every day
Active Comparator: Part B, Arm 2
Ezetimbe
Drug: Part B, Ezetimibe
Subjects will receive oral ezetimibe daily
Other: Part B, Placebo (administered subcutaneously)
Subjects will receive subcutaneous placebo every month.
Experimental: Part C, Arm 1
Evolocumab
Drug: Part C, Evolocumab
Subjects will receive subcutaneous evolocumab every 2 weeks or monthly

  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
  • 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:

  • 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: NCT01984424

  Hide Study Locations
Locations
United States, California
Research Site
Beverly Hills, California, United States, 90211
Research Site
Huntington Beach, California, United States, 92648
Research Site
Los Angeles, California, United States, 90048
Research Site
San Pedro, California, United States, 90732
United States, Georgia
Research Site
Atlanta, Georgia, United States, 30322
United States, Illinois
Research Site
Sterling, Illinois, United States, 61081
United States, Kansas
Research Site
Kansas City, Kansas, United States, 66160
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21201
Research Site
Towson, Maryland, United States, 21204
United States, Michigan
Research Site
Ann Arbor, Michigan, United States, 48106
United States, Minnesota
Research Site
Rochester, Minnesota, United States, 55905
United States, Missouri
Research Site
St. Louis, Missouri, United States, 63110
United States, New York
Research Site
New York, New York, United States, 10029
United States, North Carolina
Research Site
Durham, North Carolina, United States, 27705
United States, Ohio
Research Site
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Research Site
York, Pennsylvania, United States, 17405
United States, South Carolina
Research Site
Charleston, South Carolina, United States, 29425
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
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Research Site
Ashford, South Australia, Australia, 5035
Canada, British Columbia
Research Site
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
Research Site
Hamilton, Ontario, Canada, L8L 2X2
Research Site
London, Ontario, Canada, N6A 4V2
Research Site
Peterborough, Ontario, Canada, K9J 0B2
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H2W 1R7
Research Site
St-Charles-Borromee, Quebec, Canada, J6E 6J2
Canada
Research Site
Quebec, Canada, G1V 4M6
Czech Republic
Research Site
Hradec Kralove, Czech Republic, 500 05
Research Site
Praha 2, Czech Republic, 128 08
Research Site
Praha 4, Czech Republic, 140 21
Denmark
Research Site
Aarhus N, Denmark, 8200
Research Site
Glostrup, Denmark, 2600
France
Research Site
Nantes Cedex 1, France, 44093
Research Site
Paris Cedex 13, France, 75651
Research Site
Vénissieux, France, 69200
Germany
Research Site
Berlin, Germany, 13353
Research Site
Köln, Germany, 50937
Research Site
München, Germany, 80638
Italy
Research Site
Bologna, Italy, 40138
Research Site
Cagliari, Italy, 09134
Research Site
Cinisello Balsamo (MI), Italy, 20092
Research Site
Ferrara, Italy, 44100
Research Site
Perugia, Italy, 06129
Research Site
Pisa, Italy, 56124
Netherlands
Research Site
Amsterdam, Netherlands, 1105 AZ
Research Site
Rotterdam, Netherlands, 3045 PM
Research Site
Zwijndrecht, Netherlands, 3331 LZ
New Zealand
Research Site
Christchurch, New Zealand, 8011
Norway
Research Site
Oslo, Norway, 0373
Research Site
Ålesund, Norway, 6003
South Africa
Research Site
Johannesburg, Gauteng, South Africa, 2157
Research Site
Midrand, Gauteng, South Africa, 1685
Research Site
Observatory, Western Cape, South Africa, 7925
Research Site
Parow, Western Cape, South Africa, 7505
United Kingdom
Research Site
Birmingham, United Kingdom, B15 2TH
Research Site
Glasgow, United Kingdom, G12 8TA
Research Site
Newcastle upon Tyne, United Kingdom, NE1 4LP
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01984424     History of Changes
Other Study ID Numbers: 20120332
Study First Received: November 8, 2013
Last Updated: December 15, 2014
Health Authority: Netherlands: Centrale Commissie Mensgebonden Onderzoek (CCMO)
Norway: Norwegian Medicines Agency (Statens legemiddelverk)
Czech Republic: State Institute for Drug Control (SUKL)
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
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-Institute
Denmark: Danish Health and Medicines Authority
South Africa: Medicines Control Council
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

ClinicalTrials.gov processed this record on March 03, 2015