Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -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 subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin (HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors).

Official Title
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A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, 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: Placebo to Evolocumab
* Drug: Ezetimibe
* Drug: 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 Not on a statin or on a low dose statin with stable dose for at least 4 weeks History of intolerance to at least 2 statins Subject not at LDL-C goal Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks. Fasting triglycerides ≤ 400 mg/dL Exclusion Criteria: New York Heart Association (NYHA) III or IV heart failure Uncontrolled cardiac arrhythmia Uncontrolled hypertension 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 |
| --- | --- |
| 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: Placebo to Evolocumab<br>* Subcutaneous injection<br>Drug: Ezetimibe<br>* Tablet for oral administration<br>* Other names: Zetia;|
| 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: Placebo to Evolocumab<br>* Subcutaneous injection<br>Drug: Ezetimibe<br>* Tablet for oral administration<br>* Other names: Zetia;|
| 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>* Subcutaneous injection<br>* Other names: Repatha;Drug: Placebo to Ezetimibe<br>* Tablet for oral administration<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>* Subcutaneous injection<br>* Other names: Repatha;Drug: Placebo to Ezetimibe<br>* Tablet for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in 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 With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) |  | Weeks 10 and 12 | 
| Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 |  | Week 12 | 
| Percent Change From Baseline in 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 the 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 the 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 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 High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 |  | Baseline and Week 12 | 
| Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol 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