
    emerging gsk1322322 pre-clinical data id'd potentially reactive metabolites previously not seen
    that changed the risk: benefit profile and led to a termination
  
['infections, bacterial']
['gsk1322322 1200 mg', 'gsk1322322 3000 mg', 'placebo', 'moxifloxacin']

        Inclusion Criteria:

          -  Healthy as determined by a responsible and experienced physician, based on a medical
             evaluation including medical history, physical examination, laboratory tests and
             cardiac monitoring. A subject with a clinical abnormality or laboratory parameters
             outside the reference range for the population being studied may be included only if
             the Investigator feels that the finding is unlikely to introduce additional risk
             factors and will not interfere with the study procedures

          -  Male or female (of non childbearing potential) between 18 and 65 years of age
             inclusive, at the time of signing the 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 milli
             international units [mIU]/millilitre [mL] and estradiol <40 picograms [pg]/mL or <147
             picomole [pmol]/litre [L] is confirmatory)

          -  Male subjects with female partners of child-bearing potential must agree to use one of
             the following contraception methods from the time of the first dose of study
             medication until the final follow up visit - Condom plus partner use of a highly
             effective contraceptive; Abstinence, defined as sexual inactivity consistent with the
             preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar,
             ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable
             methods of contraception

          -  Body weight >=50 kilograms (kg) for men and >=45 kg for women and body mass index
             (BMI) within the range 18.5-31.0 kg/(square metre) m^2 (inclusive)

          -  Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5 x Upper limit
             of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35%) at screening and check-in (repeat allowed at
             check-in only)

          -  Serum Potassium, Calcium and Magnesium lab parameters within normal limits at
             screening and check-in (repeat allowed at check-in only)

          -  QTcB <450 milliseconds (msec) at screening and check-in

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form

        Exclusion Criteria:

          -  History/evidence of any arrhythmia (for example, first, second or third degree heart
             block, atrial fibrillation, supraventricular tachycardia, sinus bradycardia,
             junctional rhythm) or clinically significant cardiac disease or procedure(mitral valve
             regurgitation, heart murmur, angina/ischemia, congenital heart abnormalities, coronary
             artery bypass grafting (CABG) surgery or percutaneous transluminal coronary
             angioplasty (PCTA). Personal or family history of long QT syndrome

          -  Subjects with a pre-existing condition interfering with normal gastrointestinal
             anatomy or motility, hepatic and/or renal function, that could interfere with the
             absorption, metabolism, and/or excretion of the study drugs. Subjects with a history
             of cholecystectomy, inflammatory bowel disease or pancreatitis. Subjects with active
             peptic ulcer disease or a history of upper gastrointestinal bleeding

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones)

          -  History of regular alcohol consumption within 6 months of the study defined as an
             average weekly intake of >14 drinks for males or >7 drinks for females. One drink is
             equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of
             wine or 1.5 ounces (45 mL) of 80 proof distilled spirits

          -  A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody
             result, or a positive test for Human Immunodeficiency Virus (HIV) antibody within 3
             months of screening

          -  A positive pre-study drug/alcohol screen

          -  The subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first dosing day in the current
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer)

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day

          -  Unable to refrain from the 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 GlaxoSmithKline (GSK) Medical Monitor the medication will not
             interfere with the study procedures or compromise subject safety due to potential drug
             interaction

          -  History of sensitivity to any of the study medications, quinolone antibiotics,
             (including moxifloxacin), or components thereof or a history of drug or other allergy
             that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their
             participation

          -  Where participation in the study would result in donation of blood or blood products
             in excess of 500 mL within a 56 day period

          -  Pregnant females as determined by positive (serum or urine) Human chorionic
             gonadotropin (hCG) test at screening or prior to dosing

          -  Lactating females

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

          -  Subject is mentally or legally incapacitated

          -  History of sensitivity to heparin or heparin-induced thrombocytopenia

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products within 6 months prior to screening

          -  Unable to refrain from 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

          -  Exclusion criteria for screening Holter and ECG (a single repeat is allowed for
             eligibility determination): Heart rate <45 and >100 beats per minute (bpm) for males
             or <50 and >100 bpm for females; PR Interval <120 and >220 msec; QRS duration <70 and
             >120 msec; QTc interval (Bazett) >=450 msec (Note: The waveforms must enable the QT
             interval to be clearly defined); Q wave >30 msec

          -  Evidence of previous myocardial infarction (does not include ST segment changes
             associated with repolarization)

          -  Any conduction abnormality (including but not specific to left or right bundle branch
             block, Atrioventricular (AV) block [2nd degree or higher], Wolf Parkinson White [WPW]
             syndrome), sinus pauses>3 seconds, non-sustained or sustained ventricular tachycardia
             (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in
             the opinion of the principal investigator and GSK medical monitor, will interfere with
             the safety of the individual subject
      