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Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans - A randomized phase II dose-response study
- Source :
- Circulation, 105(18), 2159-2165. LIPPINCOTT WILLIAMS & WILKINS, Circulation, 105, 2159-65, Circulation, 105, 18, pp. 2159-65, Circulation, 105(18), 2159-2165. Lippincott Williams and Wilkins
- Publication Year :
- 2002
-
Abstract
- Background — Cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids between lipoproteins. High plasma levels of CETP are correlated with low HDL cholesterol levels, a strong risk factor for coronary artery disease. In earlier studies, JTT-705, a novel CETP inhibitor, was shown to increase plasma HDL cholesterol and to inhibit the progression of atherosclerosis in cholesterol-fed rabbits. This study describes the first results using this CETP inhibitor in humans. Methods and Results — In a randomized, double-blind, and placebo-controlled trial, we evaluated the efficacy and safety of daily treatment with 300, 600, and 900 mg JTT-705 in 198 healthy subjects with mild hyperlipidemia. Treatment with 900 mg JTT-705 for 4 weeks led to a 37% decrease in CETP activity ( P P P =0.017), whereas levels of triglycerides, phospholipid transfer protein, and lecithin-cholesterol acyltransferase were unaffected. In line with the increase of total HDL, a rise of HDL 2, HDL 3 , and apolipoprotein A-I was also noted. JTT-705 showed no toxicity with regard to physical examination and routine laboratory tests. Conclusions — We show that the use of the CETP inhibitor JTT-705 in humans is an effective means to raise HDL cholesterol levels with minor gastrointestinal side effects ( P =0.06). Although these results hold promise, further studies are needed to investigate whether the observed increase in HDL cholesterol translates into a concomitant reduction in coronary artery disease risk.
- Subjects :
- Adult
Male
medicine.medical_specialty
HDL
Adolescent
Lipoproteins
Dalcetrapib
Hyperlipidemias
Lipoproteïnen en atherosclerose
Dose-Response Relationship
chemistry.chemical_compound
Double-Blind Method
Anacetrapib
Physiology (medical)
Phospholipid transfer protein
Internal medicine
Cholesterylester transfer protein
medicine
Humans
Sulfhydryl Compounds
CETP inhibitor
Aged
Glycoproteins
Hypolipidemic Agents
Lipoproteins and atherosclerose
Dose-Response Relationship, Drug
biology
business.industry
Cholesterol
Cholesterol, HDL
Torcetrapib
Esters
Middle Aged
Amides
Lipids
Cholesterol Ester Transfer Proteins
Kinetics
Apolipoproteins
Endocrinology
chemistry
biology.protein
Female
lipids (amino acids, peptides, and proteins)
Drug
Carrier Proteins
Cardiology and Cardiovascular Medicine
business
Evacetrapib
Subjects
Details
- Language :
- English
- ISSN :
- 00097322
- Volume :
- 105
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- Circulation
- Accession number :
- edsair.doi.dedup.....c37f9c664f9a7ed2b945344cea8d140c