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Colitis, UlcerativePhase 1NCT01453491

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 1 study testing SRT2104 in people with Colitis, Ulcerative, run by Sirtris, a GSK Company at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Colitis, Ulcerative
What is being tested?
SRT2104
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
13 sitesUnited States
Study dates
13 Feb 2012to 18 Mar 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 27Show fewer
  • 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

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • GSK Investigational Site

    Anaheim, California, 92801

  • GSK Investigational Site

    Beavercreek, Ohio, 45432

  • GSK Investigational Site

    Bristol, Connecticut, 06010

  • GSK Investigational Site

    Chesterfield, Michigan, 48047

  • GSK Investigational Site

    Chevy Chase, Maryland, 20815

  • GSK Investigational Site

    Columbus, Ohio, 43215

  • GSK Investigational Site

    Great Neck, New York, 11021

  • GSK Investigational Site

    Jackson, Tennessee, 38305

  • GSK Investigational Site

    New York, New York, 10029

  • GSK Investigational Site

    Oklahoma City, Oklahoma, 73104

  • GSK Investigational Site

    Owensboro, Kentucky, 42303

  • GSK Investigational Site

    Raleigh, North Carolina, 27612

  • GSK Investigational Site

    Towson, Maryland, 21204

Other trials in United States

About this study

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

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.
Being tested
SRT2104
Medical subject headings
Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SRT2104Drug

    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.

Study groups in NCT01453491
Study groupRoleWhat they receive
50mg SRT2104ExperimentalSingle 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.
Receives: Drug: SRT2104
500mg SRT2104ExperimentalSingle 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.
Receives: Drug: SRT2104

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 75 days

  2. 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

    Measured: 56 days

Secondary outcomes (6)

  1. 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

    Measured: 75 days

  2. 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

    Measured: 75 days

  3. 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

    Measured: 75 days

  4. 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

    Measured: 75 days

  5. 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

    Measured: 75 days

  6. SRT2104 concentration in plasma will be measured after repeat dosing for up to 8 weeks in subjects with mild to moderate ulcerative colitis

    Measured: 56 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2011 (estimated)
  2. Study start13 Feb 2012
  3. Primary completion18 Mar 2013
  4. Study completion18 Mar 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01453491
Sponsor's protocol ID
115951
Status last verified
May 2017
First submitted
13 Oct 2011
Last updated
1 Jun 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • 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.

    PubMed 26595549

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SRT2104 in people with Colitis, Ulcerative, run by Sirtris, a GSK Company at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01453491, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2017.

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