title: Effects of NK-104, a new hydroxymethylglutaryl-coenzyme reductase inhibitor, on low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia. Hokuriku NK-104 Study Group.
abstract: The clinical efficacy of NK-104, a novel and totally synthetic hydroxymethylglutaryl-coenzyme A reductase inhibitor, was assessed in 30 patients (men/women = 15/15, mean age 51 years) with heterozygous familial hypercholesterolemia. After a placebo phase of >4 weeks, NK-104 was given at an initial dose of 2 mg/day for 8 weeks, which was increased to 4 mg/day for a further 8 weeks. As a result of 2 mg/day of NK-104 treatment, mean +/- SD of total and low-density lipoprotein cholesterol levels decreased significantly (p<0.0001) from baseline, namely from 8.80+/-1.38 to 6.11+/-1.09 mmol/L (-31%) and from 6.81+/-1.52 to 4.09+/-1.03 mmol/L (-40%), respectively. They decreased further (p<0.0001) as a result of 4-mg/day administration, to 5.52+/-0.81 mmol/L (-37%) and 3.55+/-0.85 mmol/L (-48%), respectively. Changes in high-density lipoprotein cholesterol levels failed to reach statistical significance. Serum triglyceride levels decreased significantly (p<0.0001) from baseline as a result of 4 mg/day of NK-104, from 1.99+/-1.72 to 1.35+/-0.90 mmol/L (-23%). Serum apolipoprotein B, CII, CIII, and E levels significantly decreased: mean changes from baseline at the end of the study were -41% (p<0.0001), -27% (p<0.0001), -19% (p = 0.002), and -37% (p<0.0001), respectively. On the other hand, apolipoprotein AI and All levels significantly increased as a result of the treatment: + 10% (p = 0.002) and +6% (p = 0.008), respectively. There were no adverse events observed in either clinical or laboratory findings that could be attributed to the treatment. These results suggest that the potency of NK-104 appears to be dose-dependent, and that NK-104 is safe and well tolerated in the treatment of patients with heterozygous familial hypercholesterolemia, and thus also provides a new therapeutic choice for subjects requiring lipid-modifying therapy.
authors.affiliation: The Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan. kajinami@med.kanazawa-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Kajinami
authors.forename: J
authors.initials: J
authors.lastname: Koizumi
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.forename: S
authors.initials: S
authors.lastname: Miyamoto
authors.forename: T
authors.initials: T
authors.lastname: Takegoshi
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D005260:Female; D006579:Heterozygote; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000627:therapeutic use*
chemical_list: D008055:Lipids; D008077:Lipoproteins, LDL; D011804:Quinolines; D006903:Hydroxymethylglutaryl CoA Reductases; C108475:pitavastatin