+11

(+5, +23)
 

-29

(-43, -16)
 

-37

(-54, -23)
 

-32

(-42, -23)
 

ZOCOR 80 mg/day 
74

-32

(-38, -24)
 

-37

(-46, -26)
 

+15

(+5, +23)
 

-34

(-45, -18)
 

-41

(-57, -28)
 

-38

(-49, -32)
 
Dysbetalipoproteinemia (Fredrickson type lll)

The results of a subgroup analysis in 7 patients with type lll hyperlipidemia (dysbetalipoproteinemia) (apo E2/2) (VLDL-C/TG>0.25) from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in Table 7.

Table 7: Six-week, Lipid-lowering Effects of Simvastatin in Type lll Hyperlipidemia Median Percent Change (min, max) from Baseline*  TREATMENT N Total-C LDL-C + IDL HDL-C TG VLDL-C+IDL Non-HDL-C
* The median baseline values (mg/dL) were: total-C = 324, LDL-C = 121, HDL-C = 31, TG = 411, VLDL-C = 170, and non-HDL-C = 291. 
Placebo 7 -8

(-24, +34) -8

(-27, +23) -2

(-21, +16) +4

(-22, +90) -4

(-28, +78) -8

(-26, -39)

ZOCOR 40 mg/day 
7

-50

(-66, -39)

-50

(-60, -31)

+7

(-8, +23)

-41

(-74, -16)

-58

(-90, -37)

-57

(-72, -44)

ZOCOR 80 mg/day 
7

-52

(-55, -41)

-51

(-57, -28)

+7

(-5, +29)

-38

(-58, +2)

-60

(-72, -39)

-59

(-61, -46)
 
Homozygous Familial Hypercholesterolemia

In a controlled clinical study, 12 patients 15-39 years of age with homozygous familial hypercholesterolemia received simvastatin 40 mg/day in a single dose or in 3 divided doses, or 80 mg/day in 3 divided doses. In 11 patients with reductions in LDL-C, the mean LDL-C changes for the 40- and 80-mg doses were 14% (range 8% to 23%, median 12%) and 30% (range 14% to 46%, median 29%), respectively. One patient had an increase of 15% in LDL-C. Another patient with absent LDL-C receptor function had an LDL-C reduction of 41% with the 80-mg dose.

Endocrine Function

In clinical studies, simvastatin did not impair adrenal reserve or significantly reduce basal plasma cortisol concentration. Small reductions from baseline in basal plasma testosterone in men were observed in clinical studies with simvastatin, an effect also observed with other statins and the bile acid sequestrant cholestyramine. There was no effect on plasma gonadotropin levels. In a placebo-controlled, 12-week study there was no significant effect of simvastatin 80 mg on the plasma testosterone response to human chorionic gonadotropin. In another 24-week study, simvastatin 20-40 mg had no detectable effect on spermatogenesis. In 4S, in which 4,444 patients were randomized to simvastatin 20-40 mg/day or placebo for a median duration of 5.4 years, the incidence of male sexual adverse events in the two treatment groups was not significantly different. Because of these factors, the small changes in plasma testosterone are unlikely to be clinically significant. The effects, if any, on the pituitary-gonadal axis in pre-menopausal women are unknown.
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3 D.R. Taves, Minimization: a new method of assigning patients to treatment and control groups. Clin. Pharmacol. Ther. 15 (1974), pp. 443-453

14.2 Clinical Studies in AdolescentsIn a doub