Effects Of GW876008 On The Bowel In Patients With Irritable Bowel Syndrome

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

The clinical chemistry parameters included albumin, calcium low, creatinine, glucose, magnesium, phosphorus, potassium, sodium, and bicarbonate. The total number of participants with clinical chemistry data of clinical concern have been presented.

The hematology parameters included white blood cell count, neutrophil count, hemoglobin, hematocrit, platelet count and lymphocytes. The total number of participants with hematology of clinical concern have been presented.

The acute emotional response to stress during each study visit was assessed using a 10 cm description-anchored visual analogue scale, ranging from 0 to 10, where 0=no-stress and 10=Most stressed ever. Higher scores indicated significant stress. Participants were asked to mark this before onset of stress, after 10 minutes of stress and finally after 10 minutes of recovery. After the pre-stress recordings, the period of either physiological or psychological stress were commenced and continued for 10 minutes, followed by a period of recovery for a further 10 minutes.

As an indicator of change in systemic autonomic activity, blood pressure was measured pre-stress, after 10 minutes of stress and after 10 minutes of recovery using a Dinamap.

As an indicator of change in systemic autonomic activity, HR was measured pre-stress, after 10 minutes of stress and after 10 minutes of recovery using a Dinamap.

Visceral (rectal) sensitivity to pain was measured using previously validated techniques. In brief, a 1-cm bipolar electrode (21L10) mounted on a 14-gauge Foley catheter was placed initially into the anal canal before the period of acclimatization. The stimulation parameters were set at 0.5-millisecond pulse width and 10-Hertz frequency for rectal measurements. The current was then increased slowly and the participants were asked to report when they felt it was painful (pain). Rectal measurements were made 8 cm above the anal verge. Measurements were made pre-stress, after 10 minutes of stress, and then after 10 minutes of recovery. The catheter remained in situ throughout the study but was moved from anal to rectal sites for the 2 measurements. Baseline was defined as the pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value minus the post-randomization value.

Visceral (rectal) sensitivity to perception was measured using previously validated techniques. In brief, a 1-cm bipolar electrode (21L10) mounted on a 14-gauge Foley catheter was placed initially into the anal canal before the period of acclimatization. The stimulation parameters were set at 0.5-millisecond pulse width and 10-Hertz frequency for rectal measurements. The current was then increased slowly and the participants will be asked to report when they were first aware of this (perception). Rectal measurements were made 8 centimeter above the anal verge. Measurements were made pre-stress, after 10 minutes of stress, and then after 10 minutes of recovery. The catheter remained in situ throughout the study but will be moved from anal to rectal sites for the 2 measurements. Baseline was defined as the pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value minus the post-randomization value.

RMBF was measured in response to both physiologic and psychological stress. Pre-stress readings were taken after 10 minutes of acclimatization. Readings were taken during pre-stress collections and at 5 minutes intervals during the stress and recovery period.Baseline was defined as the pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value minus the post-randomization value.