Back to resultsRandomized Placebo Controlled Efficacy And Safety Study Investigating GW876008 In Patients With Irritable Bowel Syndrome
Primary Purpose
Irritable Bowel Syndrome (IBS)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GW876008
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Irritable Bowel Syndrome (IBS) focused on measuring Irritable Bowel Syndrome safety
Eligibility Criteria
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).
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
GW876008
Placebo
Arm Description
GW876008
Placebo
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
Secondary Outcome Measures
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'.
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.
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.
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.
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.
IBS Composite Symptom Score
Investigation of possible composite symptom score was planned. The data was not collected for composite symptom score.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00421707
Brief Title
Randomized Placebo Controlled Efficacy And Safety Study Investigating GW876008 In Patients With Irritable Bowel Syndrome
Official Title
A Phase 2 PoC in IBS Patients With the CRF1 Receptor Anatgonist, GSK876008
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
October 14, 2006 (Actual)
Primary Completion Date
June 25, 2008 (Actual)
Study Completion Date
June 25, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a double-blind, placebo-controlled, randomised crossover study to investigate the efficacy and safety of GW876008
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Irritable Bowel Syndrome (IBS)
Keywords
Irritable Bowel Syndrome safety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
133 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GW876008
Arm Type
Experimental
Arm Description
GW876008
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
GW876008
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
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).
Description
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.
Time Frame
Up to Day 105 (weeks 3-6. in period 1, weeks 12-15 in period 2)
Title
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).
Description
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.
Time Frame
Up to Day 105 (weeks 1-6 in period 1 and weeks 9-15 in period 2).
Title
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
Description
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.
Time Frame
Up to Day 105
Title
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
Description
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.
Time Frame
Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)
Title
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Description
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.
Time Frame
Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)
Secondary Outcome Measure Information:
Title
Number of Participants With Improvements in Pain and Discomfort
Description
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'.
Time Frame
Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)
Title
Change From Baseline in Pain Severity Scores
Description
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.
Time Frame
Baseline (Day 1) and up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)
Title
Percentages of Pain-free Days
Description
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.
Time Frame
Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)
Title
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Description
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.
Time Frame
Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)
Title
Plasma Concentrations of GW876008 at Week 3 and 6
Description
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.
Time Frame
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
Title
IBS Composite Symptom Score
Description
Investigation of possible composite symptom score was planned. The data was not collected for composite symptom score.
Time Frame
Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)
Title
Changes in Patient Health Questionnaire-15 Somatization Scale (PHQ-15) Score With Treatment
Description
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.
Time Frame
Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)
Title
Summary of Anxiety and/or Depression on Hospital Anxiety and Depression Scale (HAD)
Description
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.
Time Frame
Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Sherwood
State/Province
Arkansas
ZIP/Postal Code
72120
Country
United States
Facility Name
GSK Investigational Site
City
Concord
State/Province
California
ZIP/Postal Code
94520
Country
United States
Facility Name
GSK Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
GSK Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
GSK Investigational Site
City
Stockbridge
State/Province
Georgia
ZIP/Postal Code
30281
Country
United States
Facility Name
GSK Investigational Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
GSK Investigational Site
City
Monroe
State/Province
Louisiana
ZIP/Postal Code
71201
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
GSK Investigational Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
GSK Investigational Site
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27408
Country
United States
Facility Name
GSK Investigational Site
City
Anderson
State/Province
South Carolina
ZIP/Postal Code
29621
Country
United States
Facility Name
GSK Investigational Site
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29651
Country
United States
Facility Name
GSK Investigational Site
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
GSK Investigational Site
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
GSK Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
GSK Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78209
Country
United States
Facility Name
GSK Investigational Site
City
Lynchburg
State/Province
Virginia
ZIP/Postal Code
24502
Country
United States
Facility Name
GSK Investigational Site
City
Truro
State/Province
Nova Scotia
ZIP/Postal Code
B2N 1L2
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3H 5S4
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3J 1N2
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3N 2V7
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M9W 4L6
Country
Canada
Facility Name
GSK Investigational Site
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7K 1J5
Country
Canada
12. IPD Sharing Statement
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Randomized Placebo Controlled Efficacy And Safety Study Investigating GW876008 In Patients With Irritable Bowel Syndrome
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