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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01984424
First received: November 8, 2013
Last updated: August 6, 2014
Last verified: August 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


Estimated Enrollment: 500
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

Contacts
Contact: Amgen Call Center 866-572-6436

  Show 48 Study Locations
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: August 6, 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

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

ClinicalTrials.gov processed this record on October 01, 2014