A double-blind, placebo-controlled, parallel group study to evaluate the effects of two regimens of GW856553, over a period of 3 months, on in-vivo macrophage activity, as assessed by FDG-PET/CT imaging, in the carotid arteries and aorta of subjects with established atherosclerosis.
- Conditions
- GW-856553 is under development as a potential anti-atherosclerosis agent for reduction of major cardiovascular events in high risk patient populations.MedDRA version: 9.1 Level: LLT Classification code 10003601 Term: Atherosclerosis
- Registration Number
- EUCTR2007-005338-35-GB
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1. Male and female subjects, between 50 and 80 years of age, inclusive, with a body weight > 50 kg and body mass index (BMI) between 19 and 35 kg/m2
2. Subjects who have either:
• experienced a CV event (i.e. acute coronary syndrome, unstable agina, CABG, PCI, stroke, MI, TIA, carotid endarterectomy), but have been clinically stable for at least 6 months since that event [note: if subject with carotid endarterectomy includedtarget vessel for TBR measurement can not be the carotid artery],
• or, have peripheral vascular disease (PVD), as indicated by;
symptoms of claudication a positive imaging/treadmill test or
reduced ankle branchial pressure index,
or, have a diagnosis of CAD corroborated by stress testing (exercise or pharmacological) or any other confirmed diagnosis of atherosclerotic arterial disease
• Individuals who have experienced a CV event or have PVD will be given preference for enrolment in the study, if they also have one of the following:
• metabolic syndrome, as defined by NCEP ATP III
• Framingham score > 20
• Current smokers (at least 1pack/day)
• Well-controlled diabetes, defined for the purposes of this study as HbA1c = 8%, or fasting blood glucose = 126mg/dL (7mmol/L)
3. Subjects must be on a stable dose of statin for at least 3 months prior to first dose of study medication. Subjects must be capable of continuing statin therapy from screening until the final follow up visit.
4. Either carotid or ascending aortic TBR=1.6, as measured on FDG-PET/CT, signifying active inflammation.
5. AST and ALT <2x ULN at screening; alkaline phospatase and bilirubin= 1.5x ULN at screening (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
6. A signed and dated written informed consent prior to admission to the study.
6. The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
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
1. Any medical history or clinically relevant abnormality identified on the screening medical examination, vital sign measurement, 12-lead ECG recording and/or clinical laboratory examination that is deemed by the principal investigator and/or medical monitor to make the subject ineligible for inclusion because of a safety concern.
2. History of heart failure defined as NYHA class II - IV or those with known severe LV systolic dysfunction (EF<30%) regardless of symptomatic status
3. Subjects with atrial fibrillation (AF) at screening will be excluded
4. Type 1 or Type 2 diabetes requiring insulin therapy.
5. Diabetics with fasting glucose > 126mg/dL (7mmol/L) or HbAc1 levels > 8%, at screening [note: fasting glucose to be checked again at first FDG-PET scan, and if glucose > 11mmol/L at that visit, subject will be excluded from study]
6. A positive pre-study hepatitis B surface antigen or hepatitis C antibody results within 3 months of screening.
7. Current or chronic history of liver disease, or known hepatic or biliar abnormalities (with the exception of Glibert's syndrome or asymptomatic gallstones).
8.. Renal impairment with creatinine clearance of <40 ml/min at screening, or history of kidney transplant or history of contrast nephropathy.
9. Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic inflammation (e.g. Inflammatory Bowel Disease).
10. Subjects with chronic infections such as HIV, gingivitis, periodonitis, prostatitis, gastritis, and urinary tract infections, or any active diseases, including active tuberculosis or a history of active tuberculosis.
11. Subjects with any acute infection, symptoms suggestive of sinusitis, or significant trauma (burns, fractures)
12. History of malignancy within the past 5 years, other than non-melanoma skin cancer.
13. History of skeletal muscle myopathy or rhabdomyolysis
14. Previous exposure to GW856553.
15. Current use of steroids (inhaled or oral).
16. Subjects who have donated more than 500 mL of blood within 56 days prior to the study medication administration.
17. Participation in a clinical study where the subject has received a drug or new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of the drug (whichever is longer) prior to the first dose of study medication
18. History of alcohol/drug abuse or dependence within 12 months of the study
19. The subject has a three month prior history of regular alcohol consumption exceeding an average weekly intake of >28 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of > 21 units (or an average daily intake of greater than 2 units) for females. 1 unit is equivalent to a halfpint (284mL) of beer/lager; 25mL measure of spirits or 125mL of wine; or a positive alcohol breath test at the screening visit
20. A positive urine test for drugs of abuse (not related to known medications the subject is taking, e.g. codeine for pain management) or alcohol at screening or prior to study medication administration.
21. QTc interval > 450 msec (using average va
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method