Rationale and design of a randomized study to assess the efficacy and safety of evolocumab in patients with diabetes and dyslipidemia: The BERSON clinical trial.

Type 2 diabetes mellitus (T2DM) is a major independent risk factor for cardiovascular disease, and diabetic dyslipidemia is a major contributor to cardiovascular risk in these patients. Here we report the rationale and design of a phase 3, double-blind study specifically designed to evaluate the lipid-lowering efficacy of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab in patients with T2DM and hyperlipidemia or mixed dyslipidemia who are on background statin therapy. In the BERSON (evolocumaB Efficacy for LDL-C Reduction in subjectS with T2DM On background statiN) trial, patients with T2DM, a screening low-density lipoprotein cholesterol (LDL-C) level of ≥ 2.6 mmol/L (≥100 mg/dL) or ≥ 3.4 mmol/L (≥130 mg/dL), and with or without statin treatment at screening, respectively, were enrolled and started on atorvastatin 20 mg/day for a lipid stabilization period of at least 4 weeks. Then, patients were randomly assigned in a 2:2:1:1 ratio to receive atorvastatin 20 mg once daily plus either evolocumab 140 mg every 2 weeks (Q2W), evolocumab 420 mg every month (QM), placebo Q2W, or placebo QM. The co-primary outcome measures were the percentage change from baseline in LDL-C at week 12 and the percentage change from baseline in LDL-C at the mean of weeks 10 and 12. The BERSON trial has completed enrollment. The study completed in the first half of 2018, and will provide information on the efficacy and safety of evolocumab in patients with T2DM and dyslipidemia.