The purpose of this study is to look at the safety and tolerability of increasing single doses of GSK2330672 in healthy volunteers.

This is a single blind, randomized, placebo-controlled, dose escalating, crossover, first time in human study to examine safety, tolerability, pharmacokinetic and pharmacodynamic parameters of GSK233672. Single blind indicates that the subjects and investigator are blinded to treatment but the GSK study team could be unblinded for ongoing review of interim safety data required for dose escalation.

Subjects will participate in 4 dosing periods. Subjects will enter the clinic prior to dinner time on the evening of Day -1 of each period and will remain in residence through the morning of Day 3. Barring any safety or tolerability concerns, subjects will be released at this time provided they have had at least 1 bowel movement after dosing in the clinic.

Subjects will return for their next scheduled dosing period. This process will be repeated for each dosing period. Subjects will return approximately 1 week after check out from their last dosing period for a follow up visit. Subjects will receive standardized meals meeting specific criteria starting with dinner on Day-1 and continuing through Day 1. Standard meals will be provided for the remainder of their stay in the clinic. After an overnight fast, subjects will take their study drug on the morning of Day 1. Dosing will be followed by breakfast and frequent blood sampling to assess pharmacokinetic and pharmacodynamic parameters. Scheduled assessments of heart rate, blood pressure, respiratory rate, ECGs, and clinical laboratories will be obtained to monitor subject safety. Subjects will be connected to cardiac telemetry monitors and will periodically undergo spirometry testing of ventilation parameters. Stool form and frequency of bowel movements will be recorded. All fecal samples will be collected from participants for 48 hours after dosing of study drug, or until they have had at least 1 bowel movement after dosing, whichever occurs first.

Inclusion Criteria:

• healthy volunteer
• 18-60 yrs of age
• for subjects age 50 and above: negative fecal occult blood test within 3 months prior to expected start of dosing, and normal results from sigmoidoscopy or colonoscopy within 5 yrs prior to dosing.
• if female, must be of non-childbearing potential

Exclusion Criteria:

• pregnant or breastfeeding females
• positive HIV
• positive Hep B, or Hep C within 3 months of screening
• positive drugs of abuse screening
• triglycerides > 250 mg/dL
• current or chronic history of liver disease
• any gastrointestinal or gastrointestinal related conditions that could affect fat or bile acid reabsorption
• pancreatitis
• colon cancer or 1st degree relative who has had colon cancer
• abnormal lung function tests
• inability to perform lung function tests
• unwilling to abstain from smoking, alcohol, caffeine, illicit drugs as directed by the site staff
• exposure to more than 4 new chemical entities in the 12 months prior to the first dosing day.
• where participation in the study would results in donation of more than approximately 550mL of blood in a 56-day period.

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