Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01453491
Other study ID # 115951
Secondary ID
Status Completed
Phase Phase 1
First received October 13, 2011
Last updated May 31, 2017
Start date February 13, 2012
Est. completion date March 18, 2013

Study information

Verified date May 2017
Source GlaxoSmithKline
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 17
Est. completion date March 18, 2013
Est. primary completion date March 18, 2013
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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 TNFa 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
SRT2104
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.

Locations

Country Name City State
United States GSK Investigational Site Anaheim California
United States GSK Investigational Site Beavercreek Ohio
United States GSK Investigational Site Bristol Connecticut
United States GSK Investigational Site Chesterfield Michigan
United States GSK Investigational Site Chevy Chase Maryland
United States GSK Investigational Site Columbus Ohio
United States GSK Investigational Site Great Neck New York
United States GSK Investigational Site Jackson Tennessee
United States GSK Investigational Site New York New York
United States GSK Investigational Site Oklahoma City Oklahoma
United States GSK Investigational Site Owensboro Kentucky
United States GSK Investigational Site Raleigh North Carolina
United States GSK Investigational Site Towson Maryland

Sponsors (2)

Lead Sponsor Collaborator
Sirtris, a GSK Company GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary SRT2104 concentration in plasma will be measured after repeat dosing for up to 8 weeks in subjects with mild to moderate ulcerative colitis 56 days
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04989907 - A Study in Adults With Ulcerative Colitis (UC) or Crohn's Disease (CD) Receiving Vedolizumab in Real-World Practice in Switzerland
Completed NCT03494764 - Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares Phase 2
Recruiting NCT03937609 - TITRATE (inducTIon for acuTe ulceRATivE Colitis) Phase 4
Completed NCT00503243 - Safety and Efficacy of SPD476 (Mesalazine) Given Twice Daily (2.4 g/Day) vs SPD476 Given as a Single Dose (4.8 g/Day) in Subjects With Acute Mild to Moderate Ulcerative Colitis Phase 3
Completed NCT03606499 - Real-world Effectiveness of Ustekinumab in Participants Suffering From Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis) With Extra-intestinal Manifestations or Immune-mediated Inflammatory Diseases
Completed NCT02537210 - Aminosalicylic Acid Withdrawal Study in Long Standing Inactive Ulcerative Colitis N/A
Active, not recruiting NCT02316678 - Patient Attitudes and Preferences for Outcomes of Inflammatory Bowel Disease Therapeutics N/A
Completed NCT00488631 - An Efficacy and Safety Study of Golimumab (CNTO 148) in Participants With Moderately to Severely Active Ulcerative Colitis Phase 3
Completed NCT00928681 - A Study To Investigate The Safety And Efficacy Properties Of PF-00547659 In Patients With Active Ulcerative Colitis Phase 1
Recruiting NCT05242484 - A Study of Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis Phase 2
Completed NCT01036022 - Effect of GSK1399686 in Patients With Mild to Moderately Active Ulcerative Colitis Phase 2
Recruiting NCT03841045 - Unraveling a Potential Connection Between Bilirubin Metabolism, Gut Microbiota and Inflammatory Bowel Diseases
Active, not recruiting NCT05528510 - A Study of Guselkumab Therapy in Participants With Moderately to Severely Active Ulcerative Colitis Phase 3
Completed NCT02825914 - CAsein GLycomacropeptide in Ulcerative Colitis - Anti-Inflammatory and Microbiome Modulating Effects (CAGLUCIM) N/A
Recruiting NCT06049017 - A Study of JNJ-77242113 in Participants With Moderately to Severely Active Ulcerative Colitis Phase 2
Completed NCT04567628 - Study of Relationship Between Vedolizumab Therapeutic Drug Monitoring, Biomarkers of Inflammation and Clinical Outcomes
Withdrawn NCT05999708 - A First Time in Human Study to Evaluate the Safety and Tolerability of GSK4381406 in Healthy Participants Phase 1
Recruiting NCT05611671 - A Study to Evaluate MORF-057 in Adults With Moderately to Severely Active UC Phase 2
Active, not recruiting NCT03596645 - A Study to Assess the Efficacy and Safety of Golimumab in Pediatric Participants With Moderately to Severely Active Ulcerative Colitis Phase 3
Completed NCT03648541 - BI 655130 Long-term Treatment in Patients With moderate-to Severe Ulcerative Colitis Phase 2