NCT01375764

Brief Summary

The primary objective was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia unable to tolerate an effective dose of a statin.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
160

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2011

Shorter than P25 for phase_2

Geographic Reach
8 countries

42 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 16, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 17, 2011

Completed
1 month until next milestone

Study Start

First participant enrolled

July 28, 2011

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 8, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 8, 2012

Completed
3.6 years until next milestone

Results Posted

Study results publicly available

December 23, 2015

Completed
Last Updated

November 7, 2022

Status Verified

November 1, 2022

Enrollment Period

10 months

First QC Date

June 16, 2011

Results QC Date

September 2, 2015

Last Update Submit

November 4, 2022

Conditions

Keywords

Proprotein convertase subtilisin/kexin type 9 (PCSK9)CholesterolHigh CholesterolRaised CholesterolElevated CholesterolStatin intolerantHypercholesterolemia

Outcome Measures

Primary Outcomes (2)

  • Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

    LDL-C was measured using ultracentrifugation. Least squares (LS) means are based off an analysis of covariance (ANCOVA) model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.

    Baseline and Week 12

  • Percent Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe

    LDL-C was measured using ultracentrifugation. LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.

    Baseline and Week 12

Secondary Outcomes (10)

  • Change From Baseline in LDL-C at Week 12

    Baseline and Week 12

  • Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe

    Baseline and Week 12

  • Percent Change From Baseline in Non-HDL-C at Week 12

    Baseline and Week 12

  • Percent Change From Baseline in Non-HDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe

    Baseline and Week 12

  • Percent Change From Baseline in Apolipoprotein B at Week 12

    Baseline and Week 12

  • +5 more secondary outcomes

Study Arms (5)

Ezetimibe

ACTIVE COMPARATOR

Participants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.

Drug: EzetimibeOther: Placebo to Evolocumab

Evolocumab + Ezetimibe

EXPERIMENTAL

Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.

Biological: EvolocumabDrug: Ezetimibe

Evolocumab 280 mg

EXPERIMENTAL

Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Biological: Evolocumab

Evolocumab 350 mg

EXPERIMENTAL

Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Biological: Evolocumab

Evolocumab 420 mg

EXPERIMENTAL

Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Biological: Evolocumab

Interventions

EvolocumabBIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha
Evolocumab + EzetimibeEvolocumab 280 mgEvolocumab 350 mgEvolocumab 420 mg

Administered orally once a day

Also known as: Zetia
Evolocumab + EzetimibeEzetimibe

Administered by subcutaneous injection

Ezetimibe

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female ≥ 18 to ≤ 75 years of age
  • On a statin or a low dose statin with stable dose for at least 4 weeks
  • Lipid lowering therapy has been stable prior to enrollment
  • Fasting triglycerides must be \< 400 mg/dL.
  • Subject not at LDL-C goal

You may not qualify if:

  • New York Heart Association (NYHA) III or IV heart failure or known left ventricular ejection fraction \< 30%
  • Uncontrolled cardiac arrhythmia
  • Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
  • Type 1 diabetes or newly diagnosed type 2 diabetes (HbA1c \> 8.5%)
  • Uncontrolled hypertension

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (42)

Research Site

Anaheim, California, 92801, United States

Location

Research Site

Mission Viejo, California, 92691, United States

Location

Research Site

Westlake Village, California, 91361, United States

Location

Research Site

Atlanta, Georgia, 30338, United States

Location

Research Site

Atlanta, Georgia, 30342, United States

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Research Site

Savannah, Georgia, 31406, United States

Location

Research Site

Auburn, Maine, 04210, United States

Location

Research Site

Chevy Chase, Maryland, 20815, United States

Location

Research Site

Butte, Montana, 59701, United States

Location

Research Site

Henderson, Nevada, 89052, United States

Location

Research Site

Las Vegas, Nevada, 89117, United States

Location

Research Site

New York, New York, 10029, United States

Location

Research Site

Raleigh, North Carolina, 27609, United States

Location

Research Site

Akron, Ohio, 44311, United States

Location

Research Site

Cincinnati, Ohio, 45212, United States

Location

Research Site

Bristol, Tennessee, 37620, United States

Location

Research Site

Camperdown, New South Wales, 2015, Australia

Location

Research Site

Sydney, New South Wales, 2022, Australia

Location

Research Site

Melbourne, Victoria, 3004, Australia

Location

Research Site

Perth, Western Australia, 6000, Australia

Location

Research Site

Brussels, 1200, Belgium

Location

Research Site

Uccle, 1180, Belgium

Location

Research Site

Saint John’s, Newfoundland and Labrador, A1A 3R5, Canada

Location

Research Site

St. John's, Newfoundland and Labrador, A1A 3R5, Canada

Location

Research Site

Lachine, Quebec, H8S 2E4, Canada

Location

Research Site

Ballerup Municipality, 2750, Denmark

Location

Research Site

Vejle, 7100, Denmark

Location

Research Site

Helsinki, 00029, Finland

Location

Research Site

OYS, 90029, Finland

Location

Research Site

Zaragoza, Aragon, 50009, Spain

Location

Research Site

Zaragoza, Aragón, 50009, Spain

Location

Research Site

Barcelona, Catalonia, 08036, Spain

Location

Research Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Research Site

Reus, Catalonia, 43204, Spain

Location

Research Site

Barcelona, Cataluña, 08036, Spain

Location

Research Site

L'Hospitalet de Llobregat, Cataluña, 08907, Spain

Location

Research Site

Reus, Cataluña, 43204, Spain

Location

Research Site

Göteborg, 411 36, Sweden

Location

Research Site

Gothenburg, 411 36, Sweden

Location

Research Site

Lund, 222 21, Sweden

Location

Research Site

Stockholm, 111 35, Sweden

Location

Research Site

Stockholm, 141 86, Sweden

Location

Related Publications (1)

  • Sullivan D, Olsson AG, Scott R, Kim JB, Xue A, Gebski V, Wasserman SM, Stein EA. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA. 2012 Dec 19;308(23):2497-506. doi: 10.1001/jama.2012.25790.

    PMID: 23128163BACKGROUND

Related Links

MeSH Terms

Conditions

HyperlipidemiasHypercholesterolemia, Autosomal Dominant, 3Hypercholesterolemia

Interventions

evolocumabEzetimibe

Condition Hierarchy (Ancestors)

DyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

AzetidinesAzetinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Study Director
Organization
Amgen Inc.

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 16, 2011

First Posted

June 17, 2011

Study Start

July 28, 2011

Primary Completion

May 8, 2012

Study Completion

May 8, 2012

Last Updated

November 7, 2022

Results First Posted

December 23, 2015

Record last verified: 2022-11

Locations