Randomized Placebo Controlled Efficacy And Safety Study Investigating GW876008 In Patients With Irritable Bowel Syndrome

Study Overview
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Brief Summary
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This is a double-blind, placebo-controlled, randomised crossover study to investigate the efficacy and safety of GW876008

Official Title
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A Phase 2 PoC in IBS Patients With the CRF1 Receptor Anatgonist, GSK876008

Conditions
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Irritable Bowel Syndrome (IBS)

Intervention / Treatment
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* Drug: GW876008
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has been diagnosed with IBS consistent with the Rome II Criteria as adapted in Appendix 3 of the protocol The subject has normal results from a flexible sigmoidoscopy, colonoscopy, or a flexible sigmoidoscopy plus barium enema, according to subject's age, within 5 years of randomization. Otherwise, the appropriate procedure(s) must be performed and normal results obtained during the 7-day procedure window (prior to randomization): If the subject is < 50 years of age and has not had a colonic examination within 5 years of the Screening Visit, flexible sigmoidoscopy, or colonoscopy must be performed. If the subject is = 50 years of age and has not had a colonic examination within 5 years of the Screening Visit, a colonoscopy or flexible sigmoidoscopy plus barium enema must be performed. Colonic procedure results must be known prior to randomization into the study and dispensing study medication During the two-week screening phase, the subject must have conducted self assessments on = 10 days of 14 day (with 80% compliance on daily IVRS calls) compliance assessment using the telephone data entry system Exclusion Criteria: As a result of any of the medical interview, physical examination, evaluation of mental state and psychiatric history or screening investigations the physician Subject reported no stool for 7 consecutive days during the two-week screening phase responsible considers the subject unfit for the study The subject has a 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, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, haematological, or neurological condition).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GW876008<br>GW876008 | Drug: GW876008<br> <br> |
| Placebo Comparator: Placebo<br>Placebo | Drug: GW876008<br> <br> Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Average Adequate Relief Rate During the Last 4 Weeks of the Treatment Periods (Weeks 3-6. in Period 1, Weeks 12-15 in Period 2). | 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. | Up to Day 105 (weeks 3-6. in period 1, weeks 12-15 in period 2) | 
| Number of Participants With Changes in Weekly Adequate Relief Rates During the Treatment Periods (Weeks 1-6 in Period 1 and Weeks 9-15 in Period 2). | 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. | Up to Day 105 (weeks 1-6 in period 1 and weeks 9-15 in period 2). | 
| Number of Participants With Adequate Relief of IBS Pain and Discomfort on All 4 of the Last 4 Weeks of the Treatment Phase Treatment Periods 1 and 2 | 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. | Up to Day 105 | 
| Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen | 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. | Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2) | 
| Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale | 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. | Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Improvements in Pain and Discomfort | Number of participants with improvements in pain and discomfort on GIS were presented. 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 on specified time points. Responder = Yes if A responder answered either 'moderately improved' or 'substantially improved'. | Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2) | 
| Change From Baseline in Pain Severity Scores | Pain severity scores from the 11-point scale and it's corresponding change from Baseline scores was summarized by treatment group for the last 4 weeks (i.e. weeks 3-6 and Weeks 12-15) of treatment period. Scale from 0 to 10, 0 meaning no pain, 10 worst possible pain. Lower values represent a better outcome. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting baseline value from specified time point value. Reported data values are lesser than minimum score on scale as change from Baseline is reported. | Baseline (Day 1) and up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2) | 
| Percentages of Pain-free Days | Abdominal pain free days are those days where the participant reported a score of '0' for abdominal pain at its worst. Abdominal Pain (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain. | Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2) | 
| Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function | The GIS 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. Number of participants who showed improvement and changes on the scale were presented. Participants were counted as Yes if they scored 1-3, and as No if they scored 4-7. | Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2) | 
| Plasma Concentrations of GW876008 at Week 3 and 6 | For Week 3, 6, 9, 12, and 15 visits blood samples were collected at: pre-dose (after the pre ECG measurement and just before am dose) and immediately following the 1-3 hour post-dose ECG measurement and concentration of GW876008 was analyzed. Data for Week 3 and 6 was presented. | Week 3 and 6 visits. Pre-dose [after the pre Electrocardiogram (ECG) measurement and just before am dose] and immediately following the 1-3 hour post-dose ECG measurement | 
| IBS Composite Symptom Score | Investigation of possible composite symptom score was planned. The data was not collected for composite symptom score. | Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2) | 
| Changes in Patient Health Questionnaire-15 Somatization Scale (PHQ-15) Score With Treatment | The PHQ-15 comprised of 15 somatic symptoms from the PHQ, each symptom scored from 0 to 2, where 0 (Not bothered at all), 1 (Bothered a little) 2 (bothered a lot). This questionnaire was completed at screening, and all study visits. Total score range was 0-30, where 0 indicated Not bothered at all and 30 indicated bothered a lot. Higher score indicated greater severity of somatization symptoms. | Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2) | 
| Summary of Anxiety and/or Depression on Hospital Anxiety and Depression Scale (HAD) | HAD Scale was used to assess the severity of symptoms of anxiety and depression in participants. There were 14 questions. Seven questions related to depression and seven questions related to anxiety. Participants rated the severity of symptoms in the answer to each question. There were four options in each answer, from which participants had to select one. Responses were scored on a scale of 0, 1, 2 or 3, where 0 indicated best and 3 indicated worse. Total score ranged from 0-42 where 0 indicated absence of symptoms and higher scores indicated higher anxiety/depression complains. This questionnaire was completed at screening, and all study visits. | Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Irritable Bowel Syndrome safety