SCH 48461, an inhibitor of gastrointestinal absorption of
cholesterol, was evaluated for its effects on
lipid parameters in patients with primary
hypercholesterolemia 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 (placebo 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
lovastatin 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 reduction from baseline in directly measured
low-density lipoprotein cholesterol (
LDL-C) levels than patients in the placebo group (p < or = 0.03). Overall, the percent reductions 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 reduced
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
lovastatin-treated group compared to placebo. This study demonstrated a clinically and statistically significant
cholesterol-lowering effect of
SCH 48461 in patients with primary
hypercholesterolemia.