A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Administering Multiple Oral Doses of GSK1292263 Alone and With Atorvastatin

This compound has been studied in healthy subjects and subjects with type II diabetes and is
now being studied in subjects with dyslipidemia. Because many patients with dyslipidemia are
on statins, it is important to study how GSK1292263 behaves when taken with a potent statin,
atorvastatin. The cholesterol lowering drug, ezetimibe, is included for comparison.

Inclusion Criteria:

- Healthy adult males and females of non-child-bearing-potential, aged 18-75 years who
is capable of giving informed consent.

- 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. In questionable cases, a blood sample with simultaneous
follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol <40 pg/ml (<140
pmol/L) is confirmatory in the absence of a clear post-menopausal history.

- Females on hormone replacement therapy (HRT) must discontinue HRT to allow
confirmation of post-menopausal status prior to study enrollment. For most forms
of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the
blood draw; this interval depends on the type and dosage of HRT. Following
confirmation of their post-menopausal status, they can resume use of HRT during
the study.

- Male subjects must agree to use one of the contraception methods listed in the
protocol. This criterion must be followed from the time of the first dose of study
medication until seven days following the last dose.

- Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19.0 and 39.0
(inclusive).

- Part A: (i) Subjects who are on 80mg or 40mg atorvastatin for >= 4 weeks and are
tolerating the drug well, or (ii) Subjects not on lipid-modifying therapy who have a
fasting low density lipoprotein cholesterol (LDLc) >= 130mg/dL.

- In Part B at Screening: Subjects who are on statins or Vytorin treatment for >= 4
weeks.

- Part B at the end of the 4 week washout: Subjects who have a fasting LDL cholesterol
of >=120mg/dL and <=180mg/dL and fasting triglycerides of >=100mg/dL and <=400mg/dL.

- Part B at the end of the 4 week run-in on atorvastatin: Subjects who are tolerating
well atorvastatin 10mg or 80mg (as determined by the Investigator).

- Part B: Subjects must be willing to discontinue statins or Vytorin for the duration of
the study.

- Liver enzymes, AST and ALT < 2x upper limit of normal (ULN); alkaline phosphatase and
bilirubin =< 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%). Subjects with Gilbert's syndrome are allowed
to participate in the study.

- Average QTcB or QTcF < 450msec; or QTc < 480msec in subjects with right bundle branch
block.

Exclusion Criteria:

- A medical history of the following:

- Clinical or angiographic cardiovascular disease, including history or current
evidence of coronary heart disease, heart failure, cerebrovascular disease
(including stroke and transient ischemic attack [mini-stroke]), peripheral
vascular disease. Subjects pending diagnostic procedures for any of those
conditions at the time of screening will not be eligible for participation.

- Homozygous familial hypercholesterolemia or family history of familial
hypercholesterolemia (Part B only). Note: Subjects with heterozygous familial
hypercholesterolemia on 80mg atorvastatin who are tolerating this drug well and
fulfill the other eligibility criteria may participate in Part A only.

- History of recurrent or unexplained muscle aches (e.g., fibromyalgia), myopathy
or myositis, whether or not it is related to treatment with statins or other
lipid modifying drugs.

- Renal impairment as defined by a calculated glomerular filtration rate < 60
mL/min

- History of diabetes mellitus, or history of post-prandial and/or random blood
glucose > 200 mg/dl or fasting glucose > 125 mg/dL or currently taking diabetes
medications to manage fasting glucose levels (e.g., thiazolidinediones,
sulfonylureas, insulin, metformin).

- History of pancreatitis within 10 years of screening.

- Any concurrent serious illness (e.g., severe chronic obstructive pulmonary
disease, sleep apnea, 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.

- Current or chronic history of liver disease, or known hepatic or biliary
abnormalities.

- Active peptic ulcer disease and/or history of peptic ulcer disease or
gastrointestinal bleeding within 12 months prior to screening.

- History of kidney stones within 10 years of screening.

- History of uncorrected thyroid dysfunction or an abnormal thyroid function test
assessed by thyroid stimulating hormone (TSH) at Screening. (NOTE: subjects with
hypothyroidism on a stable dose of thyroid replacement therapy for at least 3
months prior to screening and who have a screening TSH within the normal range
may participate.)

- Symptomatic cholelithiasis or obstructive or inflammatory gallbladder disease
within 3 months prior to screening.

- Gastrointestinal disease that could affect fat or bile acid absorption, or the
pharmacokinetics or pharmacodynamics of the study drugs, including inflammatory
bowel disease, chronic diarrhea, Crohn's disease or malabsorption syndromes
within the past year.

- Gastrointestinal surgery that may affect the pharmacokinetics or pharmacodynamics
of the study drugs.

Note: Subjects may be enrolled in the study if they have had a cholecystectomy three or
more months before the time of screening and are stable and asymptomatic.

- Subjects taking ezetimibe monotherapy, fibrates, bile acid binding resins, nicotinic
acid or fat absorption inhibitors are not eligible for Parts A and B.

- For females a hemoglobin < 11.5g/dL, and for males a hemoglobin < 12.5g/dL.

- Current inadequately controlled hypertension (blood pressure >= 160mmHg systolic or >=
100mmHg diastolic at screening). If blood pressure medication is changed as a result
of screening, blood pressure will be re-measured after 6 weeks and must again meet
these criteria.

- Significant electrocardiogram (ECG) abnormalities, defined as follows:

Heart Rate < 50 and >100bpm PR Interval <120 and > 220ms QRS duration < 70 and >120ms QTC
Interval (Bazett) > 450ms Or, has clinically significant rhythm abnormalities identified
during 24-hour screening Holter assessment. Subjects with left bundle branch block are
excluded from the study. Subjects with partial right bundle branch block may be considered
for inclusion following consultation with the GlaxoSmithKline (GSK) Medical Monitor.
Subjects with Wolf-Parkinson-White (WPW) syndrome are excluded from the study.

- Creatinine phosphokinase (CPK) >= 2x ULN at screening.

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.

- A positive test for HIV antibody.

- The subject has a positive pre-study drug-of-abuse 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 ml) of wine or 12 ounces (360
ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.

- Subjects will be excluded if they require treatment with systemic corticosteroids.

- 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 or untoward reaction to the study medications (GSK1292263,
atorvastatin or ezetimibe), or components thereof or a history of drug or other
allergy that, in the opinion of the physician responsible, contraindicates their
participation.

- History of intolerance to statins.

- Any change in concomitant medication (including multivitamins, herbal remedies,
dietary supplements, and over-the-counter medication) within six weeks prior to
screening that is not approved by GSK.

- On a diet that may affect study outcomes, or any change in diet, exercise habits or
smoking status within six weeks prior to screening or planned change during study
(e.g., new exercise program) other than that in the dietary instructions in the Study
Procedures Manual.

- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
dose of study medication, unless in the opinion of the Investigator and GSK Medical
Monitor the medication will not interfere with the study procedures or compromise
subject safety.

- Where participation in study would result in donation of blood in excess of
approximately 500mL within a 56 day period.

- Subject is mentally or legally incapacitated.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Pregnant females as determined by positive urine hCG test at screening or prior to
dosing.

- Lactating females.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or
pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior
to the first dose of study medication.

- Unwilling to abstain from caffeine-or xanthine-containing products from Day -2 until
Day 15.

- Subject is either an immediate family member of a participating investigator, study
coordinator, employee of an investigator; or is a member of the staff conducting the
study.