study of pharmacokinetics and pharmacodynamics effects of gsk256073a on healthy volunteers

Conditions: Healthy Subjects; Dyslipidaemias

Summary: the purpose of this study is to compare the effects of single and repeat doses of gsk256073 with placebo in hvt subjects.


Eligibility criteria:
inclusion criteria: * healthy adult males or females between 18 and 55 years of age, inclusive. * female subjects must be of non-childbearing potential * body weight \> 50 kg (110 pounds) and body mass index (bmi) 19 and 31 where: * subjects with qtc \< 450 msec at screening (or qtc \< 480 msec for subjects with bundle branch block). * a signed and dated written informed consent prior to admission to the study. * the subject is able to understand and comply with protocol requirements, instructions and protocol-stated restriction exclusion criteria: * systolic blood pressure \< 100 mmhg or 150 mmhg and/or diastolic blood pressure = 100 mmhg at screening. * history of significant cardiac arrhythmias * active peptic ulcer disease (pud) and/or history of pud within 1 year. * a serum uric acid concentration 8mg/dl * screening test positive for h. pylori using the non-radioactive breath test * history of gout and/or hyperuricemia * history of gilbert's syndrome * a serum creatinine concentration above the normal reference range * history of kidney stones * pt and/or aptt above the reference range * history of recurrent indigestion, stomach upset or diarrhea * liver function tests (lfts) or creatinine phosphokinase (cpk) 1.5x uln * screening stool test positive for occult blood * screening peripheral blood smear with abnormal rbcs * cbc, mcv, and/or reticulocyte count corrected for haemoglobin level above the reference range at screening * reduced g6pd activity * serum haptoglobin outside the reference range at screening * total serum ldh \> 1.25% above the uln at screening * positive hiv, hepatitis b or hepatitis c at screening * the subject has a positive pre-study urine drug/ serum alcohol screen. * history of alcohol consumption exceeding, on average, 7 drinks/week for women or 14 drinks/week for men within 6 months of the first dose of study medication or a positive alcohol test at screening * history of use of tobacco or nicotine containing products within 6 months of screening or a positive urine cotinine screen * use of prescription (including hormone replacement therapy) or non-prescription drugs and vitamins within 7 days or 5 half-lives prior to administration of study medication. an exception is acetaminophen which is allowed at doses of 2g/day. * use of dietary/herbal supplements within 14 days prior to treatment with study medication * treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing. * exposure to more than four new chemical entities within 12 months prior to the first dosing day. * history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. * where participation in study would result in donation of blood in excess of 500 ml within a 56 day period. * unwillingness of male subjects to use a condom/spermicide * pregnant or nursing women. * history of flushing (\>1 episode annually). * fasting blood glucose 110 mg/dl and/or history of type i or type ii dm * history of intra-ocular pathology * history of recurrent gum bleeding * history of bleeding haemorrhoids

Keywords: dose escalation gsk256073a,