A Phase 1b Study to Assess the Safety and Anti-inflammatory Effects of Two Different Doses of SRT2104 in Patients With Ulcerative Colitis

Exclusion Criteria

• •Suspicion of Crohn's disease, indeterminate colitis, microscopic colitis, segmental colitis associated with diverticulosis, ischemic colitis, or radiation-induced colitis based on medical history, endoscopy, and/or histological findings
• •Presence of infectious colitis as evidenced by positive stool culture for enteric pathogens or positive stool Clostridium difficile cytotoxin assay at Visit 1
• •Presence of chronic liver disease, with the exception of known Gilbert's syndrome
• •A positive pre-study Hepatitis B surface antigen, Hepatitis C antibody or HIV at Visit 1
• •Past or present disease that is judged by the investigator to have the potential to interfere with the study procedures or compromise the subject's safety
• •History of malignant neoplasm within the past 5 years, other than localized basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ that has been resected or definitively treated with standard approaches
• •Prior diagnosis of flat colonic dysplasia or unresected raised colonic dysplasia (adenoma-like lesion or mass)
• •History of regular alcohol consumption within 6 months of the Screening (Visit 1) defined as an average weekly intake of \>14 drinks (one drink is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits) or presence of recreational drug abuse or dependence
• •Known bleeding disorders
• •Bowel surgery within 12 months prior to Visit 1
• •History of colectomy or partial colectomy
• •Treatment with oral aminosalicylates at doses \>4.8 g per day or aminosalicylate dose modification (except transient shift lasting up to 3 days) within 4 weeks prior to study Day -5 (Note: if on this type of treatment, the dose must remain constant throughout the study treatment period)
• •Treatment with rectal aminosalicylates at any dose within 2 weeks of study Day -5
• •Treatment with systemic or rectal corticosteroids within 4 weeks of study Day -5
• •Treatment with TNFα inhibitors or other biologics within 2 months prior to study Day -5
• •Treatment with other immunosuppressants (azathioprine or 6-mercaptopurine), if initiated within 3 months prior to study Day -5, or if changed in terms of dose within 3 months prior to study Day -5 (Note: if on this type of treatment, the dose must remain constant throughout the study treatment period)
• •Regular use of pro-biotic or prebiotic preparations within 4 weeks of study Day -5 visit
• •Regular use of non-steroidal anti-inflammatories (NSAIDS) or aspirin, except low dose (cardioprotective ≤325 mg/day) aspirin, within 7 days prior to study Day -5
• •Participation in a clinical trial and treatment with an study drug within 3 months prior to Visit 1
• •Have a clinically significant finding on a chest X-ray performed at Visit 1 or within 3 months of Visit 1
• •Have an abnormal 12-lead electrocardiogram (ECG) with one or more changes considered to be clinically significant on medical review
• •Renal or liver impairment based on laboratory values obtained at Visit 1 and defined as:
• •* serum creatinine level of ≥1.4 mg/dL for females and ≥1.5 mg/dL for males, or
• •* AST and/or ALT ≥2x upper limit of normal (ULN), or
• •* bilirubin \> 1.5xULN (an isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%)
• •* Hemoglobin less than 8.5 g/dL at Visit 1
• •* Have any other reason which, in the opinion of the investigator, would confound the conduct or interpretation of the study