COLT, Multicenter CaPre ® Open Label Randomized Dose-Ranging Phase II Trial to Assess Efficacy/Safety in Patients with Mild-to-High Hypertriglyceridemia

Background: Long-chain polyunsaturated omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to reduce hepatic secretion of TG rich lipoproteins and plasma TG levels. CaPre® is a novel highly purified omega-3 krill oil extract with a high content of EPA and DHA phospholipid conjugates. Objective/Purpose: To evaluate the efficacy of CaPre® to reduce fasting plasma TG ranging between 200-877 mg/dL after 4 and 8 weeks vs. Standard Of Care (SOC). Additional endpoints were changes in TC, LDL-C, HDL-C, non-HDL-C, and HbA1c. Methods: Total of 288 patients from 34 centers aged 18-75 were randomized to Standard of Care (SOC), or CaPre® given daily with dose doubling at week 4 for 0.5g, 1g, and 2g groups while the 4g group was dosed for 8 weeks. Standard safety assessments were performed during the trial. Statistical analysis was performed using ANOVA followed by post-hoc contrast analysis assessing % change between baseline, week 4 and 8 with CaPre® compared to SOC. Results: CaPre® SOC-compared 4-week TG % difference was -8% (p=NS), -16% (p=0.007), -13% (p=0.025) and -18% (p=0.002), for 0.5g, 1g, 2g, and 4g, respectively, while the SOC-compared 8-week TG % difference was 2% (p=NS), 16% (p=0.021), -6% (p=NS) and -14% (p=0.038), for 0.5g, 1g, 2g, and 4g, respectively. CaPre® 4g SOC-compared 8-week TC % difference was -7% (p=0.06) and while the nonHDL-C was -10% (p=0.036). Similarly to beneficial lipid effects, HbA1c was significantly lowered with CaPre® 2g (-18%, p=0.013) and 4g (-15%, p=0.039). CaPre® was safe, well-tolerated, with incidence of AEs similar to SOC. Conclusions: CaPre® at daily doses of 1g-4g was effective and safe in reducing serum triglycerides and increasing HDL-C without deleterious effects on increasing LDL-C in patients with mild-to-high hypertriglyceridemia (NCT01516151).