A Study to Investigate the Effect of Rosuvastatin (CRESTOR®) on High Density Lipoprotein Kinetics in Patients With the Metabolic Syndrome

Condition(s) targeted: Metabolic Syndrome; Dyslipidemia

Intervention: Rosuvastatin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
Gerald F. Watts, BSc PhD MD, Principal Investigator, Affiliation: University Department of Medicine, Royal Perth Hospital, University of Western Australia

The purpose of this study is to investigate the dose-related effect of treatment with rosuvastatin on production and fractional catabolism of apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), and on the plasma apoA-I, apoA-II and high-density lipoprotein cholesterol (HDL-C) concentration.

Official title: A Randomised, Double-Blind, Placebo Controlled, Crossover Dose-Ranging Study to Investigate the Effect of Rosuvastatin (CRESTOR®) on High Density Lipoprotein Kinetics in Patients With the Metabolic Syndrome

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study

Primary outcome: Determine the dose-related effect of treatment with rosuvastatin on production & fractional catabolism of apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), & on the plasma apoA-I, apoA-II & high-density lipoprotein cholesterol (HDL-C) c

Secondary outcome:

Determine the dose-related effect of treatment with rosuvastatin on cellular cholesterol efflux,total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-LDL-C, triglyceride & pre1-HDL concentrations,HDL2,HDL3 cholesterol ratio

Cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activity

Lathosterol and campesterol, total apolipoprotein B (apoB), nonesterified fatty acids (NEFA) and apolipoprotein C-III (apoC-III) plasma concentrations.

Minimum age: 30 Years. Maximum age: 70 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Signed informed consent

- male aged 30 to 70 years of age

- LDL-C <6 mmol/L

- HDL-C ≤1. 2 mmol/L

- at least 2 of the following:

- insulin resistance (fasting glucose >6 mmol/L or insulin >10 mU/L or HOMA score >2. 5)

- central obesity (waist circumference >=94 cm).

- plasma triglycerides >=1. 7 and <4. 5 mmol/L.

- blood pressure >=130/ >=85 mm Hg or on drug treatment for hypertension

Exclusion Criteria:

- LDL cholesterol >=6 mmol/L

- pre-existing or history of cardiovascular disease, diabetes, renal dysfunction,

anaemia, history of significant dyspepsia or gastrointestinal disease

- apolipoprotein genotype E2/E2

Research Site, Perth, Western Australia, Australia

Starting date: April 2004
Last updated: December 6, 2006