Atherosclerotic Carotid Disease
Conditions
Interventions
Product Name: Lipitor 10 mg tablets (overencapsulated)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Atorvastatin
Concentration unit: mg
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria are met: 1. Signed written informed consent prior to beginning study-related procedures (subject must understand the aims, investigational procedures and possible consequences of the study). 2. Male or female aged 18 to 80 years of age at Screen. Female subjects must be of non-childbearing potential (post-menopausal females who have been amenorrheic >1 year, or pre-menopausal females with a documented hysterectomy or bilateral oophorectomy). 3. Positive USPIO-enhanced MRI of carotid plaque confirmed by a consultant neuroradiologist. This is defined as a signal decrease of =10% in 2 or more quadrants between pre-Sinerem and post-Sinerem MRI scans. 4. Must either be statin naïve or have been on a stable dose of a statin1 for =4 weeks prior to screening, with no evidence of statin intolerability. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Required continued use of non-statin lipid modifying therapies (e.g. fibric acid derivatives, niacin, resins, ezetimibe, fish oil supplements, etc.) or therapy with any other lipid regulating medications not specified as study treatment in the protocol.2 2. History of statin intolerance. 3. History of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody), or other chronic hepatic disorders; or ALT or AST >1.5 x ULN, or alkaline phosphatase or total bilirubin >1.5 x ULN of laboratory reference range at screening. 4. Renal impairment with creatinine clearance 400 mg/dl (4.52 mmol/L) at screening. 12. Untreated or uncontrolled hypothyroidism or thyrotoxicosis. 13. Patients with poorly controlled diabetes mellitus with HbA1c =8.5%. 14. Patients with poorly controlled hypertension (SBP=160 mmHg and/or DBP=100 mmHg). 15. History of malignancy within the past 2 years, other than non-melanoma skin cancer. 16. Evidence of recent ( 8 oz (240 ml) daily], itraconazole, ketoconazole, etc.). 20. Chronic use of NSAIDS and oral steroids therapy.3 21. Chronic use of immunosuppressants (cyclosporine, methotrexate, etc.). 22. Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication. 23. Any other subject the investigator and GSK medical monitor deems unsuitable for the study (e.g., due to either medical
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To establish whether inflammatory activity of the atherosclerotic plaque, as measured by USPIO-enhanced MRI, can be modified after the administration of high- or low- dose of atorvastatin.; Secondary Objective: • To investigate MRI-derived tensile stress in carotid plaques following the administration of high or low dose atorvastatin. • To quantify changes in cerebral micro-embolization occurring in patients with carotid plaques treated with high and low dose atorvastatin • To investigate the effects of high and low dose of atorvastatin on selected soluble plasma biomarkers • To compare macrophage content as determined by USPIO-enhanced MRI with histology of carotid plaques following the administration of high or low dose atorvastatin. • To assess appearance of new lesions on brain MR and correlate these with USPIO uptake in the carotid plaque and micro-embolic burden. • To assess the pharmacokinetic parameters of atorvastatin. ;Primary end point(s): • Changes from baseline in USPIO-enhanced MRI signal in carotid plaques at 6 weeks | — |
Countries
United Kingdom
Outcome results
None listed