Irritable Bowel Syndrome (IBS)
Conditions
Interventions
Product Name: N/A
Product Code: GW876008
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: N/A
Current Sp
Sponsors
GlaxoSmithKline Research and Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: •Subjects are male or female aged 18-65 years, inclusive with irritable bowel syndrome •For the purpose of this study, eligibility will be determined by the clinical diagnosis of IBS guided by Rome II criteria (see Appendix 3). In addition, the subject will complete a daily diary card for a minimum of 14 days. If the subject reports diarrhoea on >70% of the days, the subject will be excluded. •Have completed the screening period (minimum of 14 days) with diarrhoea /= 50 kg (110 lbs) for men and >/= 45 kg (100 lbs) for women and BMI within the range 18.5-29.9 kg/m2 inclusive. •Non-smoker (abstinence from smoking for at least 6 months before the start of the study). •Normal electrocardiogram (subjects must have no clinically significant abnormalities on a 12-lead ECG. •If the subject is 50 years of age and has not had a colonic examination within years of the Screening Visit, a colonoscopy or flexible sigmoidoscopy plus barium enema must be performed. •Signed and dated written informed consent prior to admission to the study. •The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: •Female subjects who are pregnant or nursing. •Female subjects taking oral contraceptives or other hormonal therapy. •Subjects who have taken any medication for the treatment of IBS within 6 months prior to screening. •Subjects who are taking NSAIDs on a regular basis or within 48 hours of a study day. •As a result of any of the medical interview, physical examination, evaluation of mental state and psychiatric history or screening investigations the physician responsible considers the subject unfit for the study. •The subject has a positive pre-study urine drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. •A positive pre-study HIV1/2, Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of the start of the study. •The subject has an active psychiatric illness (defined as a HAD score of 7 or more). •The subject has a history of, or active eating disorder. •Any history of suicidal attempts or behaviour. •History of regular alcohol consumption averaging >7 drinks/week for women or 14 drinks/week for men (1 drink (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits) within 6 months of screening. •The subject has a screening ECG with a QTc value of >430msec or a PR interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave) or any other clinically significant ECG finding. •The subject has received an investigational drug or participated in any other research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication. •Use of other prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety. •Consumption of known or suspected inhibitors/inducers of cytochrome P450 CYP1A2 or CYP3A4/5 enzymes is prohibited from 2 weeks prior to the start of the study and until the last study assessment. These include prescription and nonprescription drugs as well as foods such as grapefruit containing foods, Seville orange juice, red wine and other fortified (with dietary supplements, health enhancers etc) foods and drinks (including orange juice), and cruciferous vegetables •History or presence of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. •An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women from the time of the first dose of study medication until 7 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To test the hypothesis that acute therapeutic effects of GW876008 in IBS patients will reverse stress-induced visceral hypersensitivity as evidenced by changes in RMBF and/or thresholds for perception and pain; thus suggesting a possible mechanism for beneficial therapeutic effects of CRF1 antagonism in irritable bowel syndrome. ; Secondary Objective: To assess the safety and tolerability of GW876008X in adults with irritable bowel syndrome. To assess the effects of GW876008X on thresholds for rectal pain sensitivity in adults with irritable bowel syndrome. ; Primary end point(s): •The change in Laser Doppler regional rectal mucosal blood flow (RMBF) measured in response to physiological stress (cold water pressor test). •The change in Laser Doppler regional rectal mucosal blood flow (RMBF) measured in response to psychological stress (dichotomous listening test). | — |
Countries
United Kingdom
Outcome results
None listed