Study to Test GSK256073 in Patients With Dyslipidemia

Inclusion Criteria

• Signed written informed consent prior to beginning study-related procedures. Subjects must understand the aims, investigational procedures and possible consequences of the study and must be able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
• Male or female 18-75 years of age at screening.
• A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea.
• Male subjects must agree to use one of several pre-specified contraception methods. This criterion must be followed from the time of the first dose of study medication until three days following the last dose.
• Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19 and 39 (inclusive)
• LDLc concentration ≥100 mg/dL at screening and within 4 weeks of randomization (if screening occurs > 4 weeks prior to randomization)
• Fasting triglyceride concentration ≤ 300 mg/dL at screening and within 4 weeks of randomization (if screening occurs > 4 weeks prior to randomization)
• HDLc ≤ 45 mg/dL for males or ≤ 55 mg/dL for females at screening and within 4 weeks of randomization (if screening occurs > 4 weeks prior to randomization)
• Subject currently receiving lipid-modifying medication(s) must agree to stop medication(s) for at least 6 weeks prior to randomization. After this washout period LDL, TG and HDL values must be remeasured and meet the above criteria prior to randomization in the study
• AST and ALT 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 20% while on or titrated off lipid lowering medication. Subjects pending diagnostic procedures for any of those conditions at the time of screening will not be eligible for participation.
• Renal impairment (for males) as defined by a calculated GFR 200 mg/dl or fasting glucose > 125 mg/dL or currently taking diabetes medications to manage fasting glucose levels (e.g. glitazones, sulfonylureas, insulin, metformin, etc.).
• History of anemia or treatment of anemia within 12 months of screening or Hgb or Hct below the lower limit of reference range for age and gender at screening
• History of pancreatitis
• Any concurrent serious illness (e.g., severe COPD, HIV positive, liver cirrhosis, history of malignancy other than skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject from completing the study
• Active peptic ulcer disease (PUD) and/or history of PUD or other gastrointestinal bleeding within 12 months prior to screening.
• History of kidney stones
• History of gout and/or hyperuricemia or taking drugs for hyperuricemia: allopurinol and/or probenecid
• History of Gilbert's syndrome
• Current inadequately controlled hypertension (blood pressure ≥160 mmHg systolic or ≥100 mmHg diastolic at screening). If blood pressure medication is changed, blood pressure will be re-measured after 6 weeks and must again meet these criteria.
• An unwillingness of subjects currently taking aspirin to reduce the daily dose to 81 mg starting 2 weeks prior to first dose and until the follow-up visit.
• Creatinine phosphokinase (CPK) 2X ULN at screening.
• A serum uric acid exceeding by ≥ 15% the upper limit of the reference range at screening.
• PT and/or aPTT above the reference range.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• The subject has a positive pre-study drug screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• History of regular alcohol consumption within 6 months of the study defined as:
• An average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 m