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

Phase 2
Completed
Conditions
Hyperlipidemia
Interventions
Biological: Evolocumab
Other: Placebo to Evolocumab
Registration Number
NCT01375764
Lead Sponsor
Amgen
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
160
Inclusion Criteria
  • 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
Exclusion Criteria
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Evolocumab + EzetimibeEvolocumabParticipants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
EzetimibePlacebo to EvolocumabParticipants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab 280 mgEvolocumabParticipants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 350 mgEvolocumabParticipants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mgEvolocumabParticipants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
EzetimibeEzetimibeParticipants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab + EzetimibeEzetimibeParticipants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12Baseline and 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.

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

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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in LDL-C at Week 12Baseline and Week 12

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

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

LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.

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

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

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

LS means are based off an ANCOVA model which includes treatment group (evolocumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.

Percent Change From Baseline in Apolipoprotein B at Week 12Baseline and Week 12

LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.

Percent Change From Baseline in Apolipoprotein B at Week 12: Ezetimibe Alone Versus Evolocumab + EzetimibeBaseline and Week 12

LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe) and stratification factors as covariates.

Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12Baseline and Week 12

LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12Baseline and Week 12

LS means are based off an ANCOVA model which includes treatment group (3 evolocumab alone dose groups and the ezetimibe group) and stratification factors as covariates.

Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + EzetimibeBaseline and Week 12

LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.

Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + EzetimibeBaseline and Week 12

LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates.

Trial Locations

Locations (1)

Research Site

🇸🇪

Stockholm, Sweden

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