Abstract 1500: Efficacy and Safety of the MTP-inhibitor, AEGR-733, as Monotherapy and in Combination with Ezetimibe
Numerous studies have demonstrated the critical importance of lowering LDL-C on the reduction in CV events. While statin therapy remains the foundation of such treatment, not all patients can achieve target LDL-C level with statin monotherapy, and some patients cannot tolerate statins. Microsomal triglyceride transfer protein (MTP) represents a potential new target for lipid-lowering therapy, given its central role in the production of apo B-containing lipoproteins. Additionally, there are no human studies evaluating the additive cholesterol-lowering efficacy when combining an MTP-inhibitor with a cholesterol absorption inhibitor (CAI), a likely therapeutic option in statin-intolerant patients. AEGR-733 is a potent MTP-inhibitor in phase 2 development. In this double-blind, double-dummy study, we evaluated the lipid-lowering efficacy and safety of AEGR-733 alone and in combination with the CAI, ezetimibe. A total of 75 patients (25/arm) were randomized to one of 3 arms: AEGR-733 alone, ezetimibe 10 mg alone, or the combination of AEGR-733 plus ezetimibe 10 mg. Patients randomized to AEGR-733 were treated initially with 5 mg for 4 weeks and then force-titrated to 7.5 mg for 4 weeks followed by an additional 4 weeks at 10 mg for a total of 12 weeks of treatment. Patients randomized to ezetimibe received 10 mg over the entire 12 weeks of treatment. The primary efficacy endpoint was percent reduction in LDL-C from baseline. Secondary efficacy endpoints included changes in total cholesterol, triglycerides, non-HDL-C and HDL-C. All adverse events were captured and the Gastrointestinal symptom rating scale was used to quantify GI side effects. Results from this study will demonstrate whether therapy with the MTP-inhibitor, AEGR-733, provides a viable approach in lipid-lowering therapy that serves as an important adjunctive therapeutic tool in achieving target LDL-C levels in a greater number of patients.