Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2

Study Overview
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Brief Summary
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The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneous (SC) monotherapy every 2 weeks (Q2W) and monthly (QM), compared with placebo and ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with a 10-year Framingham risk score of 10% or less.

Official Title
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A Double-blind, Randomized, Placebo and Ezetimibe-controlled, Multicenter Study to Evaluate Safety and Efficacy of Lipid Lowering Monotherapy With AMG 145 in 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
* Biological: Placebo to Evolocumab
* Other: Placebo to Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 to ≤ 80 years of age National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) Framingham risk score of 10% or less Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L) and <190 mg/dL Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L) Exclusion Criteria: History of coronary heart disease New York Heart Association (NYHA) III or IV heart failure Uncontrolled cardiac arrhythmia Uncontrolled hypertension Diabetes mellitus (Type 1 diabetes, poorly controlled type 2 diabetes) Uncontrolled hypothyroidism or hyperthyroidism

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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) and placebo tablets once a day for up to 12 weeks. | Biological: Placebo to Evolocumab<br>* Administered by subcutaneous injection<br>Other: Placebo to Ezetimibe<br>* Administered orally once daily<br>|
| Placebo Comparator: Placebo QM<br>Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. | Biological: Placebo to Evolocumab<br>* Administered by subcutaneous injection<br>Other: Placebo to Ezetimibe<br>* Administered orally once daily<br>|
| Active Comparator: Ezetimibe (Q2W)<br>Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. | Drug: Ezetimibe<br>* Administered orally once a day<br>* Other names: Zetia;Biological: Placebo to Evolocumab<br>* Administered by subcutaneous injection<br>|
| Active Comparator: Ezetimibe (QM)<br>Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. | Drug: Ezetimibe<br>* Administered orally once a day<br>* Other names: Zetia;Biological: Placebo to Evolocumab<br>* Administered by subcutaneous injection<br>|
| Experimental: Evolocumab Q2W<br>Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;Other: Placebo to Ezetimibe<br>* Administered orally once daily<br>|
| Experimental: Evolocumab QM<br>Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;Other: Placebo to Ezetimibe<br>* Administered orally once daily<br>|

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 |  | Baseline and Week 12 | 
| Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Change From Baseline in LDL-C at Week 12 |  | Baseline and Week 12 | 
| Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL |  | Weeks 10 and 12 | 
| Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 |  | Week 12 | 
| Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in Non-HDL-C at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in Apolipoprotein B at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in Lipoprotein (a) at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in Triglycerides at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in VLDL-C at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in HDL-C 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, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia