GSK561679

The Bech Melancholia Sub-scale is extracted from the HAMD-17 and is comprised of the following 6 items: Depressed Mood, Feelings of Guilt, Work and Activities, Retardation, Anxiety Psychic, and Somatic Symptoms General. The items Depressed Mood, Feelings of Guilt, Work and Activities, Retardation, Anxiety Psychic are scored on a 5-point scale from 0 to 4 except for Somatic Symptoms General which is scored on a 3-point scale from 0 to 2 where the higher scores reflecting greater severity. The Bech Melancholia Scale total score is calculated by summing the individual response scores. The highest possible score is 22 (indicative of greater severity) and the lowest possible score is 0 (indicating absence of symptoms). Change from randomization was defined as the post-baseline value minus the value at randomization. Randomization was defined as Week 0.

Laser Doppler flowmetry measures changes in red cell flux using a probe that scans a fixed volume of tissue. Participants were examined in the left lateral position where DRT4 laser Doppler flow meter was placed against the rectal mucosa 10 centimeter (cm) above the lower limit of the anal margin, and pre-stress readings were taken after a period of 10 minutes of acclimatization in a room with an ambient temperature of 22 degrees Celsius. Physiological stress was evoked using the cold water pressor test. Participants were asked to place their hand and forearm into a container of ice-cold water at 0-4degree Celsius and were persuaded to maintain that position for as long as possible during the stress period of 10 minutes. Readings were then taken during pre-stress and at 5-minute intervals during the stress and recovery periods. Baseline was defined as the pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value minus the post-randomization value.

Laser Doppler flowmetry measures changes in red cell flux using a probe that scans a fixed volume of tissue, an indirect measure of flow can be obtained. Participants were examined in the left lateral position with no prior bowel preparation. The laser Doppler probe (DRT4 laser Doppler flow meter) was then placed against the rectal mucosa 10 centimeter above the lower limit of the anal margin, and pre-stress readings were taken after a period of 10 minutes of acclimatization in a room with an ambient temperature of 22 degrees Celsius. The dichotomous listening test was used as a psychological stressor. At the onset of stress, folk music was played into one ear and rock music into the other ear for 10 minutes. Readings were then taken during pre-stress and at 5-minute intervals during the stress and recovery periods. Baseline was defined as the pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value minus the post-randomization value.

The LSAS is an investigator-rated scale consisting of 48 questions concerning various social situations. The LSAS is the first psychiatric assessment at all post-screening visits. A qualified independent efficacy rater scored the participant's "fear or anxiety" and "avoidance" of social situations on 4-point scale : where, 0= None, 1= Mild, 2= Moderate, 3= Severe. Scores were recorded in participant's source documents. The LSAS total score was the sum of each of the forty-eight individual responses. Day 0 was Baseline and change from Baseline was calculated by subtracting Baseline value from Week 12 value. Data for adjusted mean and SE is presented.

The LSAS consisted of 24 fear responses. All individual items were rated on a scale 0 (none) -3 (severe) with higher scores indicating more severe fear. The LSAS fear subscale score was the sum of each of the 24 individual responses. If at least 22 items of the items making up the subscale of interest were present at a particular time point, the subscale score was calculated as Sum of non-missing items multiplied with 24/Number of non-missing items. If less than 22 of the items making up the score of interest were available for a participant at a particular time point, the subscale score was not calculated for that time point. Day 0 was Baseline and change from Baseline was calculated by subtracting Baseline value from Week 12 value. Data for adjusted mean and SE is presented.

The LSAS consisted of 24 avoidance responses. All individual items were rated on a scale 0 (never) -3 (always) with higher scores indicating more severe avoidance. The LSAS avoidance subscale Score was the sum of each of the 24 individual responses. If at least 22 items of the items making up the subscale of interest were present at a particular time point, the total score was calculated as Sum of non-missing items multiplied with 24/Number of non-missing items. If less than 22 of the items making up the score of interest were available for a participant at a particular time point, the subscale score was not calculated for that time point. . Day 0 was Baseline and change from Baseline was calculated by subtracting Baseline value from Week 12 value. Data for adjusted mean and SE is presented.

The SADS is a 28 item questionnaire. The total score was obtained by summing together the responses for all 28 items from the SADS questionnaire. Each individual item was rated as true or false. One point was given where items 2, 5, 8, 10, 11, 13, 14, 16, 18, 20, 21, 23, 24, 26 were marked as true and 1 point when each of the remaining items were marked as false. This gave a possible range of possible scores from 0 to 28 with higher scores indicating more severe disorder. If at least 26 of the items making up the total score were present at a particular time point, the total score was calculated as Sum of scores for non-missing items multiplied with 28/Number of non-missing items. If less than 26 of the items making up the score of interest were available for a participant at a particular time point, the total score was not calculated for that time point.

For the assessment of average adequate relief rate from IBS symptoms for a participant was planned by collecting the response of a question 'In the past seven days have you had adequate relief of your IBS pain or discomfort? However, in error, the question was not collected in the IVRS system. Therefore, data for this endpoints was not collected during this study.

For the assessment of changes in weekly adequate relief rates during the treatment periods was planned by collecting the response of a question. Overall response was defined as having achieved adequate relief in last 4 weeks. However, in error, the question was not collected in the IVRS system. Therefore, data for this endpoints was not collected during this study.

For the assessment of average adequate relief rate from IBS symptoms for a participant was planned by collecting the response of a question whether weekly adequate relief from IBS symptoms was achieved?. However, in error, the question was not collected in the IVRS system. Therefore, data for this endpoints was not collected during this study.

The GIS is comprised of ten questions, all rated on a seven point scale ranging from substantially worse (7) to substantially improved (1). GIS assesses the participant's improvement (or worsening) as assessed by the clinician on a 7-point scale: 1: very much improved; 2: much improved; 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; or 7: very much worse for diarrhea, constipation, stool frequency, stool consistency, urgency, bloating, incomplete evacuation, and straining. Values reported are less than the minimum score on scale as the rate is the proportion of the last four weeks that the participant is a responder.

The IBSQoL is a self-report quality-of-life measure specific to IBS that can be used to assess the impact of IBS and its treatment. The IBSQoL consists of 30 statements about bowel problems, which formed 9 scales: emotional health, mental health, health belief, sleep, energy, physical functioning, diet, social role, physical role and sexual relation. All 9 scales were rated on a five-point response scale ranging from 1 (always) to 5 (never). Scores for individual items were averaged to obtain a total score for each subscale of IBSQoL. Then transformed to a 0-100 scale for ease of interpretation with higher scores indicating better IBS-specific quality of life. Transformed scale score = (raw score - lowest possible scale score)/ (scale range) X 100. The data presented for individual scale.