Last updated: 11/07/2018 10:00:32
A Phase 1b study to assess the safety and anti-inflammatory effects of two different doses of SRT2104 in patients with Ulcerative Colitis
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Phase 1b, Exploratory Study to Assess the Safety, Tolerability, Colonic Tissue Exposure, and Anti-Inflammatory Effects of Two Different Doses of SRT2104 in Subjects with Mild to Moderate Ulcerative Colitis
Trial description: 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 colitis2) 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 weeks4) 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Number of participants with adverse events and incidence of adverse events will be used as a measure of safety and tolerability of 50 mg and 500 mg of SRT2104 after repeat dosing for up to eight weeks in subjects with mild to moderate ulcerative colitis
Timeframe: 75 days
SRT2104 concentration in colonic tissue will be measured via endoscopic biopsy after repeat dosing for up to 8 weeks in subjects with mild to moderate ulcerative colitis
Timeframe: 56 days
Secondary outcomes:
Endoscopic scoring of colonic lesions assessed during flexible sigmoidoscopy will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis
Timeframe: 75 days
Mayo score and Partial Mayo score will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis
Timeframe: 75 days
Simple Clinical Colitis Activity Index (SCCAI) will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis
Timeframe: 75 days
Fecal calprotectin will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis
Timeframe: 75 days
Histopathologic scoring of colonic tissue biopsies obtained via flexible sigmoidoscopy will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis
Timeframe: 75 days
SRT2104 concentration in plasma will be measured after repeat dosing for up to 8 weeks in subjects with mild to moderate ulcerative colitis
Timeframe: 56 days
Interventions:
Drug: SRT2104
Enrollment:
17
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Sands B, Joshi S, Haddad J, Freudenberg J, Oommen DE, Hoffman E, McCallum S, Jacobson E. Assessing Colonic Exposure, Safety, and Clinical Activity of SRT2104, a Novel Oral SIRT1 Activator, in Patients with Mild to Moderate Ulcerative Colitis. Inflamm Bowel Dis. 2016;22(3):607-614
Medical condition
Colitis, Ulcerative
Product
GSK2245840
Collaborators
GSK
Study date(s)
February 2012 to March 2013
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 75 years
Accepts healthy volunteers
No
- 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
- 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
Inclusion and exclusion 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
- 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
Renal or liver impairment based on laboratory values obtained at Visit 1 and defined as:
Trial location(s)
Location
GSK Investigational Site
Great Neck, New York, United States, 11021
Status
Study Complete
Location
GSK Investigational Site
Bristol, Connecticut, United States, 06010
Status
Study Complete
Location
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73104
Status
Study Complete
Location
GSK Investigational Site
Chesterfield, Michigan, United States, 48047
Status
Study Complete
Location
GSK Investigational Site
Towson, Maryland, United States, 21204
Status
Study Complete
Location
GSK Investigational Site
Anaheim, California, United States, 92801
Status
Study Complete
Location
GSK Investigational Site
Jackson, Tennessee, United States, 38305
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New York, New York, United States, 10029
Status
Study Complete
Location
GSK Investigational Site
Raleigh, North Carolina, United States, 27612
Status
Study Complete
Location
GSK Investigational Site
Beavercreek, Ohio, United States, 45432
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chevy Chase, Maryland, United States, 20815
Status
Study Complete
Location
GSK Investigational Site
Owensboro, Kentucky, United States, 42303
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2013-18-03
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Results for study 115951 can be found on the GSK Clinical Study Register.
Click hereResearchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Click hereAccess to clinical trial data by researchers
Visit website