Dose-Ranging Study of GSK2140944 in the Treatment of Subjects With Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections

Inclusion Criteria

• The subject is an adult male at least 18 years of age or an adult female at least 18 years of age who meets one of the following criteria: A female of child-bearing potential who is either 1) sexually inactive by abstinence, 2) whose sole male partner has been sterilized, or 3) uses a contraceptive method with a failure rate of 40 milli-international units per milliliter (MIU/mL) and estradiol =38 degrees Celsius); white blood cells (WBC) elevation (>10000 /cubic millimetre [mm^3] or >10% immature neutrophils regardless of WBC count); C-reactive protein > upper limit of normal (ULN). Note: Systemic markers of infection are not required for subjects >70 years of age or for known or suspected (based on blood glucose levels) diabetics.
• The subject has provided written, dated, informed consent and is willing and able to comply with the study protocol.

Exclusion Criteria

• The subject is pregnant or nursing.
• The subject has an immune-compromising illness; including known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), organ (including bone marrow) transplant recipients, hematological malignancy, and immunosuppressive therapy, including high-dose corticosteroids (e.g., greater than 40mg prednisone or equivalent per day for greater than two weeks).
• Body mass index (BMI)>= 40.0 kilogram per square meter.
• The subject has a serious underlying disease that could be imminently life-threatening, or is unlikely to survive for the duration of the study period.
• The subject has a medical condition or requires medication that may be aggravated by inhibition of acetylcholinesterase, such as: the subject has poorly controlled asthma or chronic obstructive pulmonary disease at baseline, and, in the opinion, of the investigator is not stable on current therapy; the subject has acute severe pain, uncontrolled with conventional medical management; the subject has active peptic ulcer disease; the subject has parkinson's disease; the subject has myasthenia gravis; the subject has history of seizure disorder requiring medications for control. this does not include a history of childhood febrile seizures; the subject has any evidence of mechanical obstruction of the urinary or digestive tracts.
• The subject has had a diagnosis of C. difficile infection (CDI) within 90 days of screening
• The subject has history of seizure disorder requiring medications for control. This does not include a history of childhood febrile seizures.
• The subject is a chronic abuser of alcohol or illicit substances such that it jeopardizes ability to comply with the protocol
• 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 investigator or Medical Monitor, contraindicates their participation
• The subject has a PR Interval 220 millisecond (msec)
• Corrected QT interval (QTc) >450msec or QTc >480msec for subjects with bundle branch block. Note: The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual overread. The QTc should be based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period. It is essential that the same method for calculating QTc that was used at a subjects baseline visit be used for that subject for all subsequent visits.
• The subject has QRS duration 120 msec.
• The subject has pre-existing grade II atrioventricular block or higher, history of significant vasovagal and/or syncopal episodes, episodes of symptomatic bradycardia.
• The subject has recent acute major blood loss with signs of hemodynamic instability.
• The subject has liver function tests: alanine aminotransferase (ALT) >2x ULN; alkaline phosphatase and bilirubin >=1.5xULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin 2 × ULN; alkaline ph