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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor

Conditions
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Hyperlipidemia

Intervention / Treatment
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* Biological: Evolocumab
* Drug: Ezetimibe
* Other: Placebo to Evolocumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ezetimibe<br>Participants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks. | Drug: Ezetimibe<br>* Administered orally once a day<br>* Other names: Zetia;Other: Placebo to Evolocumab<br>* Administered by subcutaneous injection<br>|
| Experimental: Evolocumab + Ezetimibe<br>Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;Drug: Ezetimibe<br>* Administered orally once a day<br>* Other names: Zetia;|
| Experimental: Evolocumab 280 mg<br>Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 350 mg<br>Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 420 mg<br>Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in LDL-C at 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. | Baseline and Week 12 | 
| 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 (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates. | Baseline and Week 12 | 
| Percent Change From Baseline in Non-HDL-C at 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. | Baseline and Week 12 | 
| Percent Change From Baseline in Non-HDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | 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 | 
| Percent Change From Baseline in Apolipoprotein B at 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. | Baseline and Week 12 | 
| Percent Change From Baseline in Apolipoprotein B at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe) and stratification factors as covariates. | Baseline and Week 12 | 
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at 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. | Baseline and Week 12 | 
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates. | Baseline and Week 12 | 
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at 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. | Baseline and Week 12 | 
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe | LS means are based off an ANCOVA model which includes treatment group (evoloumab + ezetimibe and ezetimibe alone) and stratification factors as covariates. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proprotein convertase subtilisin/kexin type 9 (PCSK9), Cholesterol, High Cholesterol, Raised Cholesterol, Elevated Cholesterol, Statin intolerant, Hypercholesterolemia