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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01984424
First Posted: November 14, 2013
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Amgen
  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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 ]
    Mean percent change from baseline in low density lipoprotein-cholesterol

  • Percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 24 Weeks ]
    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 ]
    Mean change from baseline in low density lipoprotein-cholesterol

  • Change from baseline in low density lipoprotein-cholesterol [ Time Frame: 24 Weeks ]
    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 ]
    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 ]
    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 ]
    Mean percent change from baseline in total cholesterol

  • Percent change from baseline in total cholesterol [ Time Frame: 24 Weeks ]
    Percent change from baseline in total cholesterol

  • Mean percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 22 and 24 Weeks ]
    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 ]
    Percent change from baseline in non-high density lipoprotein-cholesterol

  • Mean percent change from baseline in apolipoprotein B [ Time Frame: 22 and 24 Weeks ]
    Mean percent change from baseline in apolipoprotein B

  • Percent change from baseline in apolipoprotein B [ Time Frame: 24 Weeks ]
    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 ]
    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 ]
    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 ]
    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 ]
    Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio

  • Mean percent change from baseline in lipoprotein (a) [ Time Frame: 22 and 24 Weeks ]
    Mean percent change from baseline in lipoprotein (a)

  • Percent change from baseline in lipoprotein (a) [ Time Frame: 24 Weeks ]
    Percent change from baseline in lipoprotein (a)

  • Mean percent change from baseline in triglycerides [ Time Frame: 22 and 24 Weeks ]
    Mean percent change from baseline in triglycerides

  • Percent change from baseline in triglycerides [ Time Frame: 24 Weeks ]
    Percent change from baseline in triglycerides

  • Mean percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 22 and 24 Weeks ]
    Mean percent change from baseline in high density lipoprotein-cholesterol

  • Percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 24 Weeks ]
    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 ]
    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 ]
    Percent change from baseline in very low density lipoprotein-cholesterol


Enrollment: 511
Actual Study Start Date: December 10, 2013
Estimated Study Completion Date: November 14, 2017
Primary Completion Date: November 10, 2015 (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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01984424


  Show 58 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01984424     History of Changes
Other Study ID Numbers: 20120332
First Submitted: November 8, 2013
First Posted: November 14, 2013
Last Update Posted: July 2, 2017
Last Verified: June 2017

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

Additional relevant MeSH terms:
Hyperlipidemias
Hyperlipoproteinemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin Calcium
Ezetimibe
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs