Efficacy and safety of morning versus evening dose of controlled-release simvastatin tablets in patients with hyperlipidemia: a randomized, double-blind, multicenter phase III trial.

Kim, Sang-Hyun; Kim, Min-Kyung; Seo, Hong-Seok; Hyun, Min-Soo; Han, Kyoo-Rok; Cho, Seong-Wook; Kim, Young-Kwon; Hoon Park, Seong
Clinical therapeutics
2013Sep ; 35 ( 9 ) :1350-60.e1.
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Kim, Sang-Hyun -
Kim, Min-Kyung -
Seo, Hong-Seok -
Hyun, Min-Soo -
Han, Kyoo-Rok -
Cho, Seong-Wook -
Kim, Young-Kwon -
Hoon Park, Seong -
ABSTRACT
BACKGROUND: Flexibility in the recommended dosing time for a statin may improve patient compliance. OBJECTIVE: This study was designed to compare the efficacy and tolerability of morning and evening doses of controlled-release simvastatin in Korean adults with dyslipidemia. It was carried out as a requirement to obtain authorization from the Korean regulatory agency to market the product.

METHODS: In this prospective, randomized, double-blind, multicenter, placebo-controlled Phase III study, we randomly assigned 132 patients with hypercholesterolemia to a morning-dose group or an evening-dose group. Patients in the morning-dose group received 20 mg controlled-release simvastatin in the morning and a placebo in the evening, and those in the evening-dose group received a placebo in the morning and 20 mg controlled-release simvastatin in the evening.

RESULTS: After 8 weeks of the treatment, the difference in the mean change of LDL-C between the morning-dose and evening-dose groups was -2.78% (95% confidence interval, -7.65 to 2.10). The changes in total cholesterol, triglycerides, HDL-C, apolipoprotein A1, apolipoprotein B, and lipoprotein (a) after treatment did not differ between groups. Also, the achievement rates of the target LDL-C goal suggested by the dyslipidemia treatment guideline of the Korean Society of Lipidology and Atherosclerosis were not different. No serious adverse event was observed in either group. Mild and moderate adverse events were observed similarly in both groups.

CONCLUSIONS: Although controlled-release simvastatin significantly reduces LDL-C levels with good tolerability in Korean adults with dyslipidemia, the time of administration does not affect its efficacy. CI - ??2013 Elsevier HS Journals, Inc. All rights reserved.
keyword
controlled-release formulation; dyslipidemia; simvastatin; simvastatin administration and dosage
MESH
Aged, Anticholesteremic Agents/*administration & dosage/adverse effects/therapeutic use, Cholesterol, LDL/blood, Delayed-Action Preparations, Double-Blind Method, Drug Administration Schedule, Drug Chronotherapy, Female, Humans, Hypercholesterolemia/*drug therapy, Male, Middle Aged, Prospective Studies, Simvastatin/*administration & dosage/adverse effects/therapeutic use, Tablets, Triglycerides/blood
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The changes in total cholesterol, triglycerides, HDL-C, apolipoprotein A1, apolipoprotein B, and lipoprotein (a) after treatment did not differ between groups.
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DOI
10.1016/j.clinthera.2013.06.020.
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ICD 03
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