A Study to Evaluate Tolerability and Efficacy of Evolocumab (AMG 145) in Japanese Subjects

Study Overview
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Brief Summary
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The primary objective is to evaluate the effect of 12 weeks of subcutaneous evolocumab every 2 weeks or every 4 weeks, compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) when used in addition to statin therapy in Japanese adults with hypercholesterolemia and high cardiovascular risk.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Stable Statin Therapy in Japanese Subjects With Hypercholesterolemia and High Cardiovascular Risk

Conditions
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Hypercholesterolemia and High Risk for Cardiovascular Events

Intervention / Treatment
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* Biological: Evolocumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese adult, on statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks, fasting LDL-C greater than or equal to 115 mg/dL (3.0 mmol/L), fasting triglycerides less than or equal to 400 mg/dL (4.5 mmol/L); Exclusion Criteria: New York Heart Association (NYHA) class III or IV, poorly controlled hypertension, recently diagnosed or poorly controlled type 2 diabetes, last known left ventricular ejection fraction < 30%, myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, planned cardiac surgery or revascularization within 6 months of randomization, uncontrolled cardiac arrhythmia.

Ages Eligible for Study
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Minimum Age: 20 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: Triple


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<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<br>* Administered by subcutaneous injection<br>|
| 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 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 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 Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | LDL-C was measured using ultracentrifugation. | Baseline and Week 12 | 
| Percentage of Participants With an LDL-C Response at Week 12 | An LDL-C response was defined as LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12. LDL-C was measured using ultracentrifugation. | Week 12 | 
| Percent Change From Baseline to Week 12 in Non-HDL-C |  | Baseline and Week 12 | 
| Percent Change From Baseline to Week 12 in Apolipoprotein B |  | Baseline and Week 12 | 
| Percent Change From Baseline to Week 12 in VLDL-C |  | Baseline and Week 12 | 
| Percent Change From Baseline to Week 12 in Total Cholesterol/HDL-C Ratio |  | Baseline and Week 12 | 
| Percent Change From Baseline to Week 12 in Apolipoprotein B/Apolipoprotein A-1 Ratio |  | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese, hypercholesterolemia, high risk for cardiovascular events