Reduction of LDL cholesterol in patients with primary hypercholesterolemiaby SCH 48461: Results of a multicenter dose-ranging study

SCH 48461, an inhibitor of gastrointestinal absorption of cholesterol, was evaluated for its effects on lipid parameters in patients with primary hype rcholesterolemia in a multicenter, double-blind randomized, parallel-group study Following the baseline phase, which consisted of a 2- to 10-week drug washout and dietary stabilization phase and a 4-week placebo lead-in (plac ebo baseline phase), 190 patients were randomized to an 8-week double-blind active drug (SCH 48461 1, 6.25, 25, 100, 200, or 400 mg) or 40 mg lovastat in once daily each morning or placebo treatment phase. By week 2, patients who received SCH 48461 6.25 to 400 mg or lovastatin demonstrated greater re duction from baseline in directly measured low-density lipoprotein choleste rol (LDL-C) levels than patients in the placebo group (p less than or equal to 0.03). Overall, the percent reducfions in LDL-C from baseline increased as the dose of SCH 48461 increased, with 0.6% to 15.5% reductions from the minimum dose of 1 mg to the maximum dose of 400 mg. Lovastatin 40 mg/day r educed LDL-C by 30.7% (p < 0.01). Statistically significant decreases were also seen for total cholesterol and apolipoprotein B (apo B) with doses of 25 mg to 400 mg of SCH 48461 and lovastatin. SCH 48461 was well tolerated. There was a similar incidence of adverse events in each SCH 48461- or lovas tatin-treated group compared to placebo. This study demonstrated a clinical ly and statistically significant cholesterol-lowering effect of SCH 48461 i n patients with primary hypercholesterolemia. Journal of Clinical Pharmacol ogy, 2001;41:70-78 (C) 2001 the American College of Clinical Pharmacology.