This study is the first study in humans to assess the safety and tolerability of various doses of GSK1292263 alone, and taken with sitigliptan.

Inclusion Criteria:

• Healthy Male or female between 18 and 55 years of age
• A female subject is eligible to participate if she is of non-childbearing potential
• Male subjects must agree to use one of the contraception methods listed in the protocol
• BMI within the range 20 - 29.9 kg/m2
• Capable of giving written informed consent, which includes compliance with protocol
• QTcB or QTcF < 450msec.

Exclusion Criteria:

• The subject has a positive pre-study drug/alcohol screen
• Positive urinary cotinine levels or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• History of regular alcohol consumption within 6 months of the study
• History of sensitivity to heparin or heparin-induced thrombocytopenia
• Unable or unwilling to abstain from caffeine-or xanthine-containing products for 24 hours prior to dosing until the final post-dose assessment at each treatment level.
• Use of illicit drugs.
• Use of alcohol for 24 hours prior to dosing until final post-dose assessment at each treatment level.
• Consumption of red wine, oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until collection of the final pharmacokinetic and pharmacodynamic blood samples
• 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
• Pregnant females as determined by positive urine hCG test at screening or prior to dosing
• Lactating females
• Has a fasting triglyceride level >400mg/dL (4.45mmol/L)
• Has anemia defined by hemoglobin concentration <11.0g/dL for males or <10.0g/dL for females.
• CPK values higher than 2.5 times the upper limit of normal at screening.
• Significant ECG abnormalities
• abnormal vital signs as defined in the
• History of any gastrointestinal or hepatic conditions that could impact absorption of the investigational compound.
• Family history (first or second degree relatives) with a history of hypertrophic cardiomyopathy.
• Family history of torsade de pointes or other ventricular arrhythmias.
• Family history of unexplained sudden death.
• Evidence of early depolarization (e.g., Wolf-Parkinson-White syndrome).
• Has clinically significant rhythm abnormalities identified during 24-hour Screening Holter assessment.
• Subjects who have asthma or a history of asthma
• The subject has participated in a clinical trial and has received an investigational product within a protocol defined period
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days or 14 days if the drug is a potential enzyme inducer or 5 half-lives 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.
• 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 GSK Medical Monitor, contraindicates their participation
• Subjects who are taking low-dose aspirin for cardiovascular prophylaxis (81mg or less) are eligible to participate in the study, but the aspirin must be discontinued from Screening to the Follow-up visit
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
• Unwillingness or inability to follow the procedures outlined in the protocol.
• As a result of the medical interview, physical examination, or screening investigations, the investigator considers the subject unfit for the study.
• 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.

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.