Safety and Efficacy of Evolocumab in Combination With Statin Therapy in Adults With Diabetes and Hyperlipidemia or Mixed Dyslipidemia

Study Overview
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Brief Summary
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The primary objective of this study was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145) in combination with statin therapy (atorvastatin) on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in diabetic adults with hyperlipidemia or mixed dyslipidemia.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety and Efficacy of Evolocumab (AMG 145) in Combination With Statin Therapy in Diabetic Subjects With Hyperlipidemia or Mixed Dyslipidemia (BERSON)

Conditions
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Diabetes, Hyperlipidemia, Mixed Dyslipidemia

Intervention / Treatment
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* Biological: Evolocumab
* Drug: Atorvastatin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females with type 2 diabetes (receiving pharmacologic treatment for at least 6 months or longer) with stable diabetes therapy Lipid-lowering therapy must be unchanged for at least 4 weeks or more Subjects receiving statin therapy at screening must have a fasting LDL-C of greater than or equal to 100 mg/dL Subjects not receiving statin therapy at screening must have a fasting LDL-C of greater than or equal to 130 mg/dL Exclusion criteria: New York Heart Association (NYHA) class III or IV heart failure Uncontrolled cardiac arrhythmia Uncontrolled hypertension Type 1 diabetes or 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: Atorvastatin (Q2W)<br>Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks. | Drug: Atorvastatin<br>* Administered orally once a day<br>* Other names: Lipitor;Other: Placebo<br>* Placebo to evolocumab administered by subcutaneous injection<br>|
| Active Comparator: Atorvastatin (QM)<br>Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks. | Drug: Atorvastatin<br>* Administered orally once a day<br>* Other names: Lipitor;Other: Placebo<br>* Placebo to evolocumab administered by subcutaneous injection<br>|
| Experimental: Evolocumab Q2W + Atorvastatin<br>Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;Drug: Atorvastatin<br>* Administered orally once a day<br>* Other names: Lipitor;|
| Experimental: Evolocumab QM + Atorvastatin<br>Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;Drug: Atorvastatin<br>* Administered orally once a day<br>* Other names: Lipitor;|

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 B100 at the Mean of Weeks 10 and 12 |  | Baseline and weeks 10 and 12 | 
| Percent Change From Baseline in Apolipoprotein B100 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 | 
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 |  | Baseline and weeks 10 and 12 | 
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 |  | Baseline and week 12 | 
| Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 |  | Baseline and weeks 10 and 12 | 
| Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio 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 Less Than 70 mg/dL (1.8 mmol/L) at Week 12 |  | 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 |