a phase 1b study to assess the safety and anti-inflammatory effects of two different doses of srt2104 in patients with ulcerative colitis

Conditions: Colitis, Ulcerative

Summary: the purpose of this research study is to: * 1) test the safety and tolerability of 2 different oral doses of srt2104 in subjects with ulcerative colitis * 2) determine the amount of srt2104 measured from a single blood sample in addition to colon and/or rectal tissue samples (biopsies) * 3) determine whether srt2104 has any anti-inflammatory effect on the colon and/or rectum when taken orally for 8 weeks * 4) determine whether srt2104 causes any detectable changes to specific biomarkers. a biomarker is a biological marker (or substance such as a protein) that is used as an indicator of changes in a biological state that corresponds to the risk or progression of a disease.


Eligibility criteria:
inclusion criteria: * mild to moderately active ulcerative colitis as evidenced by mayo score 6-10 (inclusive) with rectal bleeding score ≥1, endoscopy score between 2-3 (inclusive), and physician's rating of disease activity \<3 at day -5 * colonic inflammation extending proximal to the rectum (i.e., greater than 15 cm in extent) on baseline sigmoidoscopy at day -5 * confirmed diagnosis of ulcerative colitis for at least 3 months prior to the screening visit (visit 1) * male or female between 18 and 75 years, inclusive * body weight \>50 kg and bmi ≥18 kg/m\^2 at screening (visit 1) * capable of giving written informed consent, and willing and able to comply with the requirements of the protocol * female subjects of child-bearing potential must be willing to use reliable contraception from visit 1 through the follow-up visit (day 70) 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