Evaluation of Evolocumab (AMG 145) Efficacy in Diabetic Adults With Hypercholesterolemia/Mixed Dyslipidemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of 12 weeks of subcutaneous evolocumab taken monthly compared with subcutaneous placebo taken monthly on low density lipoprotein cholesterol (LDL-C) in adults with type 2 diabetes mellitus and high blood cholesterol on a maximally tolerated oral dose of statin of at least moderate-intensity.

Detailed Description
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This study will enroll adults with type 2 diabetes mellitus and elevated LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels on a stable, maximally tolerated statin dose of at least moderate-intensity at signing of the informed consent; statin therapy must remain unchanged during screening and the remainder of the study.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Evolocumab (AMG 145) on LDL-C in Subjects With Type 2 Diabetes Mellitus and Hypercholesterolemia/Mixed Dyslipidemia

Conditions
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Hypercholesterolemia, Mixed Dyslipidemia, Type 2 Diabetes

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years Type 2 Diabetes Mellitus Hemoglobin A1c < 10% Stable diabetes therapy Must be on maximally tolerated dose of statin of at least moderate Intensity Fasting triglycerides ≤ 600 mg/dL Not at LDL-C or Non-HDL-C goal. Exclusion Criteria: Moderate to severe renal dysfunction Uncontrolled hypertension Persistent active liver disease or hepatic dysfunction Has taken a cholesterylester transfer protein inhibitor in the last 12 months, Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke within 3 months prior to randomization

Ages Eligible for Study
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Minimum Age: 18 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<br>Participants received placebo subcutaneous injection once every month (QM) for 12 weeks. | Drug: Placebo to Evolocumab<br>* Administered by subcutaneous injection with an automated mini doser<br>|
| Experimental: Evolocumab<br>Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection with an automated mini doser<br>* Other names: AMG 145;|

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 the Mean of Weeks 10 and 12 |  | Baseline and Weeks 10 and 12 | 
| Percent Change From Baseline in LDL-C at Week 12 |  | Baseline and week 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 | 
| 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 Total Cholesterol at the Mean of Weeks 10 and 12 |  | Baseline and weeks 10 and 12 | 
| Percent Change From Baseline in Total Cholesterol at Week 12 |  | Baseline and week 12 | 
| Percentage of Participants With Mean LDL-C at Weeks 10 and 12 Less Than 70 mg/dL (1.8 mmol/L) |  | Weeks 10 and 12 | 
| Percentage of Participants With LDL-C at Week 12 Less Than 70 mg/dL (1.8 mmol/L) |  | Week 12 | 
| Percentage of Participants With at Least a 50% Reduction From Baseline in Mean LDL-C at Weeks 10 and 12 |  | Baseline and weeks 10 and 12 | 
| Percentage of Participants With at Least a 50% Reduction From Baseline in LDL-C 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 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 | 
| Percent Change From Baseline in 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high cholesterol, statin intolerant, diabetes, type 2 diabetes, high blood cholesterol, hypercholesterolemia, mixed dyslipidemia