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Study to Evaluate the Pharmacodynamics of SB-656933 in Patients With Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT00748410
Recruitment Status : Terminated (SB-656933 is no longer being developed for ulcerative colitis.)
First Posted : September 8, 2008
Results First Posted : March 14, 2018
Last Update Posted : March 14, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This study will involve the use of a new compound, SB-656933. Accumulation of inflammatory white blood cells (mostly polymorphonuclear neutrophils)in the gut (colon) may be contributing to the pathology of ulcerative colitis. It has been shown that SB-656933 reduces polymorphonuclear neutrophils (PMN) accumulation in pre-clinical models of colitis. 99m-Tc-HMPAO scintigraphy is a imaging technique which will be used in this study to observe the effect of SB656933 on the migration of PMN to inflamed tissue.

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: SB-656933 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, 7-day Repeat Dose Study to Evaluate the Pharmacodynamics of SB-656933-AAA in Patients With Ulcerative Colitis.
Actual Study Start Date : January 22, 2009
Actual Primary Completion Date : December 12, 2009
Actual Study Completion Date : December 12, 2009

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: 7 Days Repeat Dose Drug: SB-656933
7 days repeat dose
Other Name: SB656933



Primary Outcome Measures :
  1. Change From Baseline at 1 and 7 Days Treatment With Daily Dose of SB-656933-AAA in 99m(Technetium-hexamethyl Derivative of Propylene Amine Oxide)Tc-HMPAO Leukocyte Single Photon Emission Computerized Tomography (SPECT) Scintigraphic Activity Scores (SAS) [ Time Frame: Baseline (Day -1) and Day 1 and 7 ]
    Data has been presented for participants since change from Baseline data was not analyzed. For scintigraphy, blood was obtained for radiolabelling. Labelled white cells were then injected for SPECT scintigraphy and scanning began 45 minutes after injection of labelled White blood cells (WBCs). SPECT images of the colon were divided into 5 segments: ascending colon, transverse colon, descending colon, sigmoid, and rectum.T he SPECT segment uptake ratio was expressed as a fraction of bone marrow activity obtained from counts in the lumbar spine. The SPECT segment uptake ratio was converted into a four-point (0 to 3) segmental SPECT severity score where grade 0 was equal to no uptake. Only 3 participants were included before the study was discontinued.It was not possible to draw any meaningful conclusions from the very limited data available. Data has been presented for the 3 participants (99001, 99002 and 99003) since the analysis was not done. Baseline was Day -1.


Secondary Outcome Measures :
  1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to follow-up (7 to 10 days after last dose) ]
    An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

  2. Vital Signs Assessment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: Day 1 and 7 ]
    Vital sign measurements included SBP and DBP at Day 1 and 7. Data was collected in supine position. It was not possible to draw any meaningful conclusions from the very limited data available. Data has been presented for the 3 participants (99001, 99002 and 99003) since the analysis was not done.

  3. Vital Signs Assessment- Heart Rate [ Time Frame: Day 1 and 7 ]
    Vital sign measurements included heart rate at Day 1 and 7. Data was collected in supine position. It was not possible to draw any meaningful conclusions from the very limited data available. Data has been presented for the 3 participants (99001, 99002 and 99003) since the analysis was not done.

  4. Changes From Baseline to After Treatment in Faecal Calprotectin Levels [ Time Frame: Day -1 and pre-dose and 8 hour post-dose on Day 1 and 7 ]
    Stool sample was collected from 1-hour post dose until 8 hours post dose for faecal calprotectin measures. It was not possible to draw any meaningful conclusions from the very limited data available. Data has been presented for the 3 participants (99001, 99002 and 99003) since the analysis was not done. Baseline was Day -1.

  5. Amount of Medicine in Blood [ Time Frame: At 1, 2.25, 4, 8 hour on Day 1 and 7 ]
    Blood samples were collected at 1, 2.25, 4, 8 hour on Day 1 and 7 for the analysis of amount of medicine in blood. It was not possible to draw any meaningful conclusions from the very limited data available. Data has been presented for the 3 participants (99001, 99002 and 99003) since the analysis was not done.



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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • A history of ulcerative colitis for at least 3 months
  • moderately active UC, either stable on medications or in a flare of the disease
  • Mayo endoscopic score of 2 or 3 within 2 days of dosing.
  • Male or female between 18 and 65 years of age
  • Women of child bearing potential must use an effective method of contraception.
  • Male subjects must agree to use one of the specified contraception method,
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal at study start.
  • Signed written informed consent
  • QTcB or QTcF < 450msec at screening

Exclusion criteria:

  • The subject has a positive pre-study drug/alcohol screen.
  • A positive test for HIV, hepatitis B or C.
  • History of regular alcohol consumption within 6 months of the study
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days or 5 half-lives prior to the first dose of study medication
  • Known allergies
  • recent participation in another trial
  • recent blood donation
  • Pregnant or lactating females
  • unwillingness or inability to follow study procedures
  • consumption of red wine, seville oranges, grapefruit or grapefruit juice in last 7 seven day before study start.
  • Mild UC, Mayo endoscopic score of 0 or 1.
  • Toxic megacolon or perforation on plain abdominal Xray.
  • Crohn's Disease, indeterminate colitis, bleeding disorders, or active ulcer disease.
  • Previous colonic surgery.
  • Current or recurrent disease, other than UC, that could affect the action, absorption or disposition of the study medication, or clinical or laboratory assessments.
  • Absolute neutrophil count below 2.0x109/L.
  • A positive culture for enteric pathogens that is clinically significant, presence of clostridium difficile toxin, or with ova and parasites detected by microscopy, or has a clinical suspicion of an infectious disease of the bowel.
  • Symptomatic GI stricture within 6 months of screening or obstructive symptoms within 3 months of screening.
  • Likely to require abdominal surgery within the study period.
  • Congenital or acquired immunodeficiency, including any immunologic diseases with gastrointestinal involvement except for UC.
  • Ongoing neoplastic disease of the bowel.
  • History of prostatitis, epididymitis, epididymal cysts, structural abnormalities or testicular cancer.
  • Subjects with abnormalities of the renal tract, renal stones or history of recurrent urinary tract infections (UTI.s).
  • Subjects with any history of autoimmune hepatitis or sclerosing cholangitis. Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden.
  • Blood pressure persistently ≥ 140/90 mmHg at screening
  • Concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, autoimmune, renal, pulmonary, hepatic, endocrine, metabolic, haematological, or neurological condition).
  • Clinically significant hepatic impairment(Evidence of cirrhosis, Clinical episodes of jaundice)
  • Current evidence of, or has been treated for a malignancy within the past 5 years.
  • BMI <18 kg.m2 or >35 kg/m2
  • Clinically significant renal laboratory values.
  • Has not discontinued any prohibited concomitant medication prior to the screening visit or within the protocol-specified time period.
  • Has not remained on a stable dose of any permitted concomitant medication(s) for the protocol-specified time period preceding the Screening Visit.
  • history of substance abuse

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00748410


Locations
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1105 AZ
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Additional Information:
Study Data/Documents: Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: CUC111342
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: CUC111342
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: CUC111342
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: CUC111342
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: CUC111342
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: CUC111342
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00748410     History of Changes
Other Study ID Numbers: CUC111342
First Posted: September 8, 2008    Key Record Dates
Results First Posted: March 14, 2018
Last Update Posted: March 14, 2018
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
URL: http://

Keywords provided by GlaxoSmithKline:
CD11b
Ulcerative colitis
99mTc-HMPAO-labelled leukocyte scintigraphy

Additional relevant MeSH terms:
Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases