Results:

A total of 406 participants were randomized to the AMG 145 treatment arms, placebo arms, and the ezetimibe arm, with approximately 45 participants per arm. The mean age of the patients was 51 years, 34% were men, and 79% were white. Mean LDL-C concentration at baseline was 3.7 mmol/L. Of the patients enrolled, 21% of patients had two or more cardiovascular risk factors, 32% had metabolic syndrome, and no one had a history of coronary artery disease. AMG 145 significantly reduced LDL-C concentrations in all dose groups. The changes from baseline were –41.0% (95% confidence interval –46.2 to –35.8) for the AMG 70 mg/2-week dose; –43.9% (–49.0 to –38.7) for the 105 mg/2-week dose; and –50.9% (–56.2 to –45.7) for the 140 mg/2-week dose. Doses given every 4 weeks also resulted in reduced LDL-C. The changes from baseline were –39.0% (–44.1 to –34.0) for the 280 mg/4-week dose; –43.2% (–48.3 to –38.1) for the 350 mg/4-week dose; and –48.0% (–53.1 to –42.9) for the 420 mg/4-week dose. The placebo groups had changes in LDL-C including placebo every 2 weeks –3.7% (–9.0 to 1.6); placebo every 4 weeks 4.5% (–0.7 to 9.8). For the ezetimibe group, the change from baseline was –14.7% (–18.6 to –10.8). Reductions observed in the AMG 145 arms were statistically different from either of the placebo arms and the ezetimibe arm (p < 0.001). Treatment-emergent adverse events occurred in 136 (50%) of 271 patients in the AMG 145 groups, 41 (46%) of 90 patients in the placebo groups, and 26 (58%) of 45 patients in the ezetimibe group; no deaths or serious treatment-related adverse events were reported.