GW-856553 is under development as a potential anti-atherosclerosis agent for reduction of major cardiovascular events in high risk patient populations
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy adult male and females between 18 and 75 years of age, inclusive. 2. To be eligible, female subjects must have a negative pregnancy test (i.e. Urine or serum B-hCG (for females) and be of: a. non-childbearing potential (i.e. physiologically incapable of becoming pregnant). This includes any female who is post-menopausal. For the purposes of this study, post menopausal is defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. Postmenopausal status will be confirmed by serum FSH and oestradiol concentrations at screening. Surgical sterility will be defined as females who have had a hysterectomy and/or bilateral oophorectomy or tubal ligation. OR b. childbearing potential and agree to commit to one of the protocol-approved methods of contraception as detailed in Section 7.3. 3. Body weight > 50 kg and body mass index (BMI) between 19 and 32kg/m2 4. Subjects with high LDLc levels, as per NCEP ATPIII criteria:fasting LDLc level > 4.1 mmol/L (160 mg/dL), inclusive. Fasting TG level should be =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of symptomatic coronary artery disease, stroke, or other known atherosclerotic disease. 2. Subjects who are current smokers and require a cigarette within 30 minutes after they wake in the morning, or cannot abstain from smoking for approximately 5 hours. 3. History of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody), or other chronic hepatic disorders. 4. History of increased liver function tests (ALT, AST) due to acute or chronic liver conditions, above the upper limit of normal in the past 6 months and/or liver function tests (bilirubin, ALT, AST) above the upper limit of normal at Screening. 5. Renal impairment with creatinine clearance of 180 mmHg systolic and/or >100mmHg diastolic) or any subject who has experienced a modified regimen of antihypertensive medication within 6 weeks prior to first dose of study medication, or any subject who is likely to commence treatment of a hypertensive medication 7. Current poorly controlled diabetes mellitus, defined as HbA1c >10% at Screen. 8. History of heart failure defined as NYHA class II - IV or those with known severe LV dysfunction (EF 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 half-pint (284mL) of beer/lager; 25mL measure of spirits or 125mL of wine; or a positive alcohol breath test at the screening visit 18. A positive urine test for drugs of abuse (not related to known medications the subject is taking, ie, codeine for pain management) or alc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of GW-856553 on endothelium function as compared to placebo in subjects with dyslipidaemia ; Secondary Objective: • To determine the effect of GW856553 on endothelium-independent vasodilation as compared to placebo in subjects with dyslipidaemia • To determine the effect of GW856553 on basal NO activity in endothelium as compared to placebo • To characterize vascular compliance modifications in response to GW856553 administration in subjects with dyslipidaemia • To assess the pharmacodynamic effect of daily doses over four weeks of GW856553 (7.5mg BD) as measured by the level of phosphorylated heat shock protein-27 (pHSP-27) in sorbitol induced whole blood cells of patients with dyslipidaemia. • Examine safety and tolerability of GW856553 ;Primary end point(s): Forearm blood flow ratio, as measured by venous occlusion plethysmography, in response to maximum dose of intra-arterial acetylcholine infusion. | — |
Countries
United Kingdom
Outcome results
None listed