A Phase 1b Study to Assess the Safety and Anti-inflammatory Effects of Two Different Doses of SRT2104 in Patients With Ulcerative Colitis
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
1 other identifier
interventional
17
1 country
13
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Feb 2012
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 13, 2011
CompletedFirst Posted
Study publicly available on registry
October 18, 2011
CompletedStudy Start
First participant enrolled
February 13, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 18, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
March 18, 2013
CompletedJune 1, 2017
May 1, 2017
1.1 years
October 13, 2011
May 31, 2017
Conditions
Outcome Measures
Primary Outcomes (2)
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
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
56 days
Secondary Outcomes (6)
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
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
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
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
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
75 days
- +1 more secondary outcomes
Study Arms (2)
50mg SRT2104
EXPERIMENTALSingle oral administration of 50mg SRT2104 study drug will be supplied as 25 mg and 250 mg capsules and will be taken orally once daily for 56 days. SRT2104 is to be taken at approximately the same time every morning, in the fasted state. Water is permitted ad libitum. Subjects are allowed to consume liquids but should refrain from eating solid food for approximately 1 hour after dosing.
500mg SRT2104
EXPERIMENTALSingle oral administration of 500mg SRT2104 will be taken orally once daily for 56 days. SRT2104 is to be taken at approximately the same time every morning, in the fasted state. Water is permitted ad libitum. Subjects are allowed to consume liquids but should refrain from eating solid food for approximately 1 hour after dosing.
Interventions
SRT2104 drug substance is a new chemical entity which is supplied as a fine, yellowish/amber powder. The SRT2104 investigational product is prepared by packing 25mg or 250 mg of micronized SRT2104 powder with no additional additives into a size 00 opaque, hard gelatin capsule. All subjects will be provided with one dosing bottle per day that contains two 25 mg or 250 mg SRT2104 capsules for oral ingestion.
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sirtris, a GSK Companylead
- GlaxoSmithKlinecollaborator
Study Sites (13)
GSK Investigational Site
Anaheim, California, 92801, United States
GSK Investigational Site
Bristol, Connecticut, 06010, United States
GSK Investigational Site
Owensboro, Kentucky, 42303, United States
GSK Investigational Site
Chevy Chase, Maryland, 20815, United States
GSK Investigational Site
Towson, Maryland, 21204, United States
GSK Investigational Site
Chesterfield, Michigan, 48047, United States
GSK Investigational Site
Great Neck, New York, 11021, United States
GSK Investigational Site
New York, New York, 10029, United States
GSK Investigational Site
Raleigh, North Carolina, 27612, United States
GSK Investigational Site
Beavercreek, Ohio, 45432, United States
GSK Investigational Site
Columbus, Ohio, 43215, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73104, United States
GSK Investigational Site
Jackson, Tennessee, 38305, United States
Related Publications (1)
Sands BE, Joshi S, Haddad J, Freudenberg JM, Oommen DE, Hoffmann E, McCallum SW, 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 Mar;22(3):607-14. doi: 10.1097/MIB.0000000000000597.
PMID: 26595549DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 13, 2011
First Posted
October 18, 2011
Study Start
February 13, 2012
Primary Completion
March 18, 2013
Study Completion
March 18, 2013
Last Updated
June 1, 2017
Record last verified: 2017-05
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.