Lifibrol: A novel lipid-lowering drug for the therapy of hypercholesterolemia*

Abstract

To determine the effects of lifibrol on serum lipids in adult patients with primary hypercholesterolemia. These were two double-blind, randomized placebo-controlled studies. Each patient in each study had an 8-week dietary lead-in period on the American Heart Association Step I diet before administration of lifibrol or placebo. The first study consisted of active dosing of 4 weeks, and the second study had 12 weeks of active dosing. The setting for the study involved outpatients in private or university hospitals in the United States. All patients had primary hypercholesterolemia with low-density lipoprotein (LDL) cholesterol levels of > 160 mg/dl after the dietary lead-in period. There were 155 patients in the 4-week study and 336 patients in the 12-week study. In the first study, patients were randomly assigned to receive either 150, 300, 450, 600, or 900 mg lifibrol as a single daily dose for 4 weeks. In the second study, patients were randomized to receive either 150, 300, or 600 mg lifibrol for 12 weeks. Efficacy was determined by serial measurements of serum lipids either on a weekly or biweekly basis during each study. Compared with baseline, lifibrol reduced LDL cholesterol (> 40%, p < 0.0001) and apolipoprotein B (approximately 40%, p < 0.0001) by 4 weeks in both studies. After 6 weeks, high-density lipoprotein (HDL) cholesterol levels increased in the placebo and 150 and 300 mg lifibrol groups. In the 600 mg lifibrol group, triglycerides (approximately 25%, p < 0.001), lipoprotein (a) (approximately 30%, p < 0.001), and HDL cholesterol (approximately 5%, p < 0.002) decreased. Lifibrol reduced key sterol intermediates (e.g., lanosterol, lathosterol, beta-sitosterol, and campesterol) and increased serum bile acids, but it had no effect on urinary mevalonic acid excretion. The pharmacokinetics of lifibrol are independent of dose and are similar in men and women. Lifibrol was well tolerated. The most frequent medical event in both studies was skin rash. Lifibrol is a potent lipid-lowering drug in patients with hypercholesterolemia.