Monoclonal Antibody Against PCSK9 to Reduce Elevated Low-density Lipoprotein Cholesterol (LDL-C) in Adults Currently Not Receiving Drug Therapy for Easing Lipid Levels

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) every 2 weeks (Q2W) or every 4 weeks (Q4W), compared with placebo, on the percent change from baseline in LDL-C when used as monotherapy in adults with hypercholesterolemia.

Official Title
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A Randomized, Placebo- and Ezetimibe-controlled, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Hypercholesterolemic Subjects With a 10-year Framingham Risk Score of 10% or Less

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 Low density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and < 190 mg/dL Framingham risk score of 10% or less Fasting triglycerides < 400 mg/dL Exclusion Criteria: History of coronary heart disease New York Heart Association (NYHA) II - IV heart failure Uncontrolled cardiac arrhythmia 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 |
| --- | --- |
| Placebo Comparator: Placebo Q2W<br>Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. | Other: Placebo to Evolocumab<br>* Administered by subcutaneous injection<br>|
| Placebo Comparator: Placebo Q4W<br>Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks. | Other: Placebo to Evolocumab<br>* Administered by subcutaneous injection<br>|
| Active Comparator: Ezetimibe<br>Participants received 10 mg ezetimibe orally once a day for 12 weeks. | Drug: Ezetimibe<br>* Administered orally once a day<br>* Other names: Zetia;|
| Experimental: Evolocumab 70 mg Q2W<br>Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 105 mg Q2W<br>Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 140 mg Q2W<br>Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|
| Experimental: Evolocumab 280 mg Q4W<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 Q4W<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 Q4W<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. | 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. | Baseline and Week 12 | 
| Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Apolipoprotein B at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 |  | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High cholesterol, Proprotein convertase subtilisin/kexin type 9 (PCSK9), Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia