Clinical trial NCT00748410: Study to Evaluate the Pharmacodynamics of SB-656933 in Patients With Ulcerative Colitis
Official title: An Open Label, 7-day Repeat Dose Study to Evaluate the Pharmacodynamics of SB-656933-AAA in Patients With Ulcerative Colitis.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colitis, Ulcerative
Keywords: CD11b
Ulcerative colitis
99mTc-HMPAO-labelled leukocyte scintigraphy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-09-08
Enrollment: 3
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: Baseline (Day -1) and Day 1 and 7
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to follow-up (7 to 10 days after last dose)
measure: Vital Signs Assessment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Day 1 and 7
measure: Vital Signs Assessment- Heart Rate
timeFrame: Day 1 and 7
measure: Changes From Baseline to After Treatment in Faecal Calprotectin Levels
timeFrame: Day -1 and pre-dose and 8 hour post-dose on Day 1 and 7
measure: Amount of Medicine in Blood
timeFrame: At 1, 2.25, 4, 8 hour on Day 1 and 7
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: