Phase IIa clinical studies with
cerivastatin--including 2 pilot US and European dose-ranging studies, and 1 US dose-scheduling study--were conducted to establish a dosage regimen and effective therapeutic doses of
cerivastatin in the treatment of
hypercholesterolemia. Both dose-ranging studies included a 10-week dietary run-in, to which placebo was added in the last 6 weeks, before patients (n = 385) were randomized to 1 of 6 4-week treatment groups:
cerivastatin (0.025, 0.05, 0.1, and 0.2 mg/day), 40 mg/day
lovastatin (US), 20 mg/day
simvastatin (Europe), or placebo. The dose-scheduling study also included a 10-week dietary run-in and 6-week single-blind placebo run-in phase, before patients (n = 319) were randomized to 4 weeks of treatment with either 0.1 mg
cerivastatin twice daily, 0.2 mg
cerivastatin with the evening meal, 0.2 mg
cerivastatin at bedtime, or placebo in a 2:2:2:1 ratio. The 4-week dose-ranging studies showed that all 4 doses of
cerivastatin produced significantly greater reductions in
low-density lipoprotein (
LDL) cholesterol than placebo.
Cerivastatin 0.2 mg decreased
LDL cholesterol by 30.5%.
Cerivastatin also significantly decreased total
cholesterol,
triglycerides, and
apolipoprotein B, and significantly increased
high-density lipoprotein (
HDL) cholesterol. Similar reductions in
LDL cholesterol and total
cholesterol occurred with 0.2 mg/day
cerivastatin in the dose-scheduling study, although the reductions were significantly greater when
cerivastatin was administered once daily with either the evening meal or at bedtime compared with 2 divided doses.
LDL cholesterol reductions were similar when
cerivastatin was taken with the evening meal and at bedtime.
Cerivastatin was well tolerated, with the incidence of adverse events comparable to that of placebo treatment. No clinically significant increases in either hepatic
isoenzymes or
creatine phosphokinase were observed
after treatment with
cerivastatin.