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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline ( Sirtris, a GSK Company )
ClinicalTrials.gov Identifier:
NCT01453491
First received: October 13, 2011
Last updated: August 1, 2013
Last verified: July 2013
  Purpose

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.

Condition Intervention Phase
Colitis, Ulcerative
Drug: SRT2104
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 [ Time Frame: 75 days ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 56 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 75 days ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 75 days ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 75 days ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 75 days ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 75 days ] [ Designated as safety issue: No ]
  • SRT2104 concentration in plasma will be measured after repeat dosing for up to 8 weeks in subjects with mild to moderate ulcerative colitis [ Time Frame: 56 days ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: February 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 50mg SRT2104
Single 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.
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.
Experimental: 500mg SRT2104
Single 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.
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01453491

Locations
United States, California
GSK Investigational Site
Anaheim, California, United States, 92801
United States, Connecticut
GSK Investigational Site
Bristol, Connecticut, United States, 06010
United States, Maryland
GSK Investigational Site
Chevy Chase, Maryland, United States, 20815
GSK Investigational Site
Towson, Maryland, United States, 21204
United States, Michigan
GSK Investigational Site
Chesterfield, Michigan, United States, 48047
United States, New York
GSK Investigational Site
Great Neck, New York, United States, 11021
GSK Investigational Site
New York, New York, United States, 10029
United States, North Carolina
GSK Investigational Site
Raleigh, North Carolina, United States, 27612
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43215
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
Sirtris, a GSK Company
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline ( Sirtris, a GSK Company )
ClinicalTrials.gov Identifier: NCT01453491     History of Changes
Other Study ID Numbers: 115951
Study First Received: October 13, 2011
Last Updated: August 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 10, 2014