Trial Outcomes & Findings for Randomized Placebo Controlled Efficacy And Safety Study Investigating GW876008 In Patients With Irritable Bowel Syndrome (NCT NCT00421707)
NCT ID: NCT00421707
Last Updated: 2018-01-31
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
133 participants
Primary outcome timeframe
Up to Day 105 (weeks 3-6. in period 1, weeks 12-15 in period 2)
Results posted on
2018-01-31
Participant Flow
A total of 132 participants with irritable bowel syndrome (IBS), as classified by the Rome II criteria for IBS, but otherwise healthy, were randomized in this study. Study was conducted at 20 centers (14 centers in united states, six centers in Canada) from 14 October 2006 to 25 June 2008
Participant milestones
| Measure |
Sequence A/X/B
As per the treatment sequence A/X/B, during period 1, eligible participants received GW876008 125 milligram (mg) (A) (1 x GW876008 100 mg and 1 x GW876008 25 mg ) once daily for 6 weeks, followed by a washout period (X) of 3 weeks where participants received matching placebo once daily followed by period 2 where participants received matching placebo (B) once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg (specific for that dispensing period) orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose pharmacokinetic (PK) blood sample.
|
Sequence B/X/A
As per the treatment sequence B/X/A, during period 1, eligible participants received matching placebo (B) once daily for 6 weeks followed by a washout period (X) of 3 weeks where participants received matching placebo once daily followed by period 2 where participants received GW876008 125 mg (A) (1 x GW876008 100 mg and 1 x GW876008 25 mg ) once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg (specific for that dispensing period) orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|
|
Period 1: Treatment Period 1
STARTED
|
67
|
65
|
|
Period 1: Treatment Period 1
COMPLETED
|
56
|
56
|
|
Period 1: Treatment Period 1
NOT COMPLETED
|
11
|
9
|
|
Period 2: Washout
STARTED
|
56
|
56
|
|
Period 2: Washout
COMPLETED
|
55
|
52
|
|
Period 2: Washout
NOT COMPLETED
|
1
|
4
|
|
Period 3:Treatment Period 2
STARTED
|
55
|
52
|
|
Period 3:Treatment Period 2
COMPLETED
|
53
|
49
|
|
Period 3:Treatment Period 2
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Sequence A/X/B
As per the treatment sequence A/X/B, during period 1, eligible participants received GW876008 125 milligram (mg) (A) (1 x GW876008 100 mg and 1 x GW876008 25 mg ) once daily for 6 weeks, followed by a washout period (X) of 3 weeks where participants received matching placebo once daily followed by period 2 where participants received matching placebo (B) once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg (specific for that dispensing period) orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose pharmacokinetic (PK) blood sample.
|
Sequence B/X/A
As per the treatment sequence B/X/A, during period 1, eligible participants received matching placebo (B) once daily for 6 weeks followed by a washout period (X) of 3 weeks where participants received matching placebo once daily followed by period 2 where participants received GW876008 125 mg (A) (1 x GW876008 100 mg and 1 x GW876008 25 mg ) once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg (specific for that dispensing period) orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|
|
Period 1: Treatment Period 1
Withdrawal by Subject
|
1
|
5
|
|
Period 1: Treatment Period 1
Adverse Event
|
7
|
2
|
|
Period 1: Treatment Period 1
Lost to Follow-up
|
2
|
2
|
|
Period 1: Treatment Period 1
Protocol Violation
|
1
|
0
|
|
Period 2: Washout
Adverse Event
|
1
|
1
|
|
Period 2: Washout
Withdrawal by Subject
|
0
|
1
|
|
Period 2: Washout
Lost to Follow-up
|
0
|
1
|
|
Period 2: Washout
Other: Pregnancy
|
0
|
1
|
|
Period 3:Treatment Period 2
Withdrawal by Subject
|
1
|
1
|
|
Period 3:Treatment Period 2
Protocol Violation
|
1
|
0
|
|
Period 3:Treatment Period 2
Adverse Event
|
0
|
2
|
Baseline Characteristics
Randomized Placebo Controlled Efficacy And Safety Study Investigating GW876008 In Patients With Irritable Bowel Syndrome
Baseline characteristics by cohort
| Measure |
Sequence A/X/B
n=67 Participants
As per the treatment sequence A/X/B, during period 1, eligible participants received GW876008 125 mg (A) (1 x GW876008 100 mg and 1 x GW876008 25 mg ) once daily for 6 weeks, followed by a washout period (X) of 3 weeks where participants received matching placebo once daily followed by period 2 where participants received matching placebo (B) once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg (specific for that dispensing period) orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose pharmacokinetic (PK) blood sample.
|
Sequence B/X/A
n=65 Participants
As per the treatment sequence B/X/A, during period 1, eligible participants received matching placebo (B) once daily for 6 weeks followed by a washout period (X) of 3 weeks where participants received matching placebo once daily followed by period 2 where participants received GW876008 125 mg (A) (1 x GW876008 100 mg and 1 x GW876008 25 mg ) once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg (specific for that dispensing period) orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Total
n=132 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44.1 Years
STANDARD_DEVIATION 11.74 • n=93 Participants
|
43.0 Years
STANDARD_DEVIATION 11.43 • n=4 Participants
|
43.5 Years
STANDARD_DEVIATION 11.56 • n=27 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=93 Participants
|
48 Participants
n=4 Participants
|
100 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
32 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
58 Participants
n=93 Participants
|
52 Participants
n=4 Participants
|
110 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Up to Day 105 (weeks 3-6. in period 1, weeks 12-15 in period 2)Population: Intent to Treat population comprised of all participants who were randomized to treatment, who received at least one dose of double blind medication and for whom at least one valid post baseline efficacy assessment was available.
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to Day 105 (weeks 1-6 in period 1 and weeks 9-15 in period 2).Population: Intent to Treat population.
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to Day 105Population: Intent to Treat population
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)Population: Intent to Treat population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
GW876008 125 mg
n=117 Participants
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=117 Participants
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
Pain and Discomfort
|
0.26 Proportion of participants responded
Standard Deviation 0.357
|
0.22 Proportion of participants responded
Standard Deviation 0.334
|
—
|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
diarrhea
|
0.30 Proportion of participants responded
Standard Deviation 0.377
|
0.28 Proportion of participants responded
Standard Deviation 0.383
|
—
|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
Constipation
|
0.18 Proportion of participants responded
Standard Deviation 0.319
|
0.16 Proportion of participants responded
Standard Deviation 0.295
|
—
|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
Stool Frequency
|
0.25 Proportion of participants responded
Standard Deviation 0.362
|
0.24 Proportion of participants responded
Standard Deviation 0.349
|
—
|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
Stool Consistency
|
0.24 Proportion of participants responded
Standard Deviation 0.370
|
0.21 Proportion of participants responded
Standard Deviation 0.345
|
—
|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
Urgency
|
0.24 Proportion of participants responded
Standard Deviation 0.365
|
0.25 Proportion of participants responded
Standard Deviation 0.363
|
—
|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
Bloating
|
0.18 Proportion of participants responded
Standard Deviation 0.329
|
0.16 Proportion of participants responded
Standard Deviation 0.287
|
—
|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
Incomplete Evacuation
|
0.19 Proportion of participants responded
Standard Deviation 0.350
|
0.16 Proportion of participants responded
Standard Deviation 0.307
|
—
|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
Straining
|
0.19 Proportion of participants responded
Standard Deviation 0.341
|
0.19 Proportion of participants responded
Standard Deviation 0.319
|
—
|
|
Mean Global Improvement Scale (GIS) Responder Rate Over the Last Four Weeks by Regimen
IBS Symptoms
|
0.32 Proportion of participants responded
Standard Deviation 0.403
|
0.26 Proportion of participants responded
Standard Deviation 0.357
|
—
|
PRIMARY outcome
Timeframe: Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)Population: Intent to Treat population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
GW876008 125 mg
n=106 Participants
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=114 Participants
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
n=112 Participants
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Emotional
|
15.35 Score on a scale
Standard Deviation 3.852
|
15.72 Score on a scale
Standard Deviation 3.674
|
15.39 Score on a scale
Standard Deviation 3.595
|
|
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Mental Health
|
21.07 Score on a scale
Standard Deviation 4.141
|
21.39 Score on a scale
Standard Deviation 3.116
|
21.21 Score on a scale
Standard Deviation 3.253
|
|
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Sleep
|
12.49 Score on a scale
Standard Deviation 2.489
|
12.47 Score on a scale
Standard Deviation 2.570
|
12.79 Score on a scale
Standard Deviation 2.551
|
|
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Energy
|
8.22 Score on a scale
Standard Deviation 1.892
|
8.25 Score on a scale
Standard Deviation 1.986
|
8.21 Score on a scale
Standard Deviation 1.870
|
|
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Physical Functioning
|
5.23 Score on a scale
Standard Deviation 1.683
|
5.63 Score on a scale
Standard Deviation 2.282
|
5.50 Score on a scale
Standard Deviation 2.067
|
|
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Food/Diet
|
14.27 Score on a scale
Standard Deviation 3.131
|
14.74 Score on a scale
Standard Deviation 2.894
|
14.60 Score on a scale
Standard Deviation 2.890
|
|
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Social
|
16.11 Score on a scale
Standard Deviation 3.783
|
16.39 Score on a scale
Standard Deviation 3.414
|
16.43 Score on a scale
Standard Deviation 3.767
|
|
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Role-Physical
|
15.16 Score on a scale
Standard Deviation 4.472
|
15.85 Score on a scale
Standard Deviation 4.189
|
15.44 Score on a scale
Standard Deviation 4.261
|
|
Ratings on Irritable Bowel Syndrome Quality of Life (IBSQoL) Scale
Sexual Relations
|
12.30 Score on a scale
Standard Deviation 3.122
|
13.10 Score on a scale
Standard Deviation 2.667
|
12.73 Score on a scale
Standard Deviation 3.056
|
SECONDARY outcome
Timeframe: Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)Population: Intent to Treat population. Only those participants available at the specified time points were analyzed.
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'.
Outcome measures
| Measure |
GW876008 125 mg
n=117 Participants
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=119 Participants
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
n=112 Participants
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Number of Participants With Improvements in Pain and Discomfort
Week 1, Yes
|
25 Participants
|
20 Participants
|
24 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 1, No
|
92 Participants
|
95 Participants
|
85 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 2, Yes
|
25 Participants
|
18 Participants
|
24 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 2, No
|
92 Participants
|
98 Participants
|
88 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 3, Yes
|
30 Participants
|
22 Participants
|
31 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 3, No
|
87 Participants
|
96 Participants
|
81 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 4, Yes
|
30 Participants
|
26 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 4, No
|
87 Participants
|
91 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 5, Yes
|
31 Participants
|
28 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 6, Yes
|
31 Participants
|
26 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 6, No
|
86 Participants
|
91 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Pain and Discomfort
Week 5, No
|
86 Participants
|
89 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)Population: Intent to Treat population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
GW876008 125 mg
n=67 Participants
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=67 Participants
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Change From Baseline in Pain Severity Scores
Stool consistency, Week 3-6
|
-0.04 Score on a scale
Standard Deviation 0.654
|
0.03 Score on a scale
Standard Deviation 0.571
|
—
|
|
Change From Baseline in Pain Severity Scores
Stool frequency, Week 3-6
|
-0.25 Score on a scale
Standard Deviation 0.905
|
-0.35 Score on a scale
Standard Deviation 0.932
|
—
|
|
Change From Baseline in Pain Severity Scores
5 point pain severity, Week 3-6
|
-0.89 Score on a scale
Standard Deviation 0.745
|
-0.87 Score on a scale
Standard Deviation 0.753
|
—
|
|
Change From Baseline in Pain Severity Scores
IBS Symptoms, Week 3-6
|
-0.58 Score on a scale
Standard Deviation 0.501
|
-0.55 Score on a scale
Standard Deviation 0.498
|
—
|
|
Change From Baseline in Pain Severity Scores
Nausea severity, Week 3-6
|
-0.27 Score on a scale
Standard Deviation 0.546
|
-0.31 Score on a scale
Standard Deviation 0.525
|
—
|
|
Change From Baseline in Pain Severity Scores
Vomitting severity, Week 3-6
|
-0.00 Score on a scale
Standard Deviation 0.072
|
-0.02 Score on a scale
Standard Deviation 0.129
|
—
|
|
Change From Baseline in Pain Severity Scores
Burping severity, Week 3-6
|
-0.36 Score on a scale
Standard Deviation 0.568
|
-0.35 Score on a scale
Standard Deviation 0.599
|
—
|
|
Change From Baseline in Pain Severity Scores
Feeling full severity, Week 3-6
|
-0.54 Score on a scale
Standard Deviation 0.729
|
-0.49 Score on a scale
Standard Deviation 0.660
|
—
|
|
Change From Baseline in Pain Severity Scores
Feeling excessively full severity, Week 3-6
|
-0.48 Score on a scale
Standard Deviation 0.726
|
-0.48 Score on a scale
Standard Deviation 0.671
|
—
|
|
Change From Baseline in Pain Severity Scores
Bloating severity, Week 3-6
|
-0.78 Score on a scale
Standard Deviation 0.798
|
-0.77 Score on a scale
Standard Deviation 0.684
|
—
|
|
Change From Baseline in Pain Severity Scores
Diarrhoea severity, Week 3-6
|
-0.43 Score on a scale
Standard Deviation 0.619
|
-0.42 Score on a scale
Standard Deviation 0.573
|
—
|
|
Change From Baseline in Pain Severity Scores
Constipation severity, Week 3-6
|
-0.31 Score on a scale
Standard Deviation 0.592
|
-0.33 Score on a scale
Standard Deviation 0.546
|
—
|
|
Change From Baseline in Pain Severity Scores
Urgency severity, Week 3-6
|
-0.58 Score on a scale
Standard Deviation 0.605
|
-0.45 Score on a scale
Standard Deviation 0.617
|
—
|
|
Change From Baseline in Pain Severity Scores
Straining severity, Week 3-6
|
-0.31 Score on a scale
Standard Deviation 0.568
|
-0.34 Score on a scale
Standard Deviation 0.556
|
—
|
|
Change From Baseline in Pain Severity Scores
Incomplete evacuation severity, Week 3-6
|
-0.47 Score on a scale
Standard Deviation 0.704
|
-0.48 Score on a scale
Standard Deviation 0.587
|
—
|
|
Change From Baseline in Pain Severity Scores
Flatulence severity, Week 3-6
|
-0.54 Score on a scale
Standard Deviation 0.632
|
-0.50 Score on a scale
Standard Deviation 0.593
|
—
|
|
Change From Baseline in Pain Severity Scores
Heartburn severity, Week 3-6
|
-0.18 Score on a scale
Standard Deviation 0.617
|
-0.17 Score on a scale
Standard Deviation 0.544
|
—
|
SECONDARY outcome
Timeframe: Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)Population: Intent to Treat population. Only those participants available at the specified time points were analyzed. Washout period was of 3 weeks only. Thus, these categories are not applicable for placebo washout arm.
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.
Outcome measures
| Measure |
GW876008 125 mg
n=117 Participants
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=119 Participants
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
n=112 Participants
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Percentages of Pain-free Days
Week 1
|
27.25 Percentage of days
Standard Deviation 33.261
|
24.38 Percentage of days
Standard Deviation 31.015
|
34.92 Percentage of days
Standard Deviation 37.032
|
|
Percentages of Pain-free Days
Week 2
|
32.72 Percentage of days
Standard Deviation 37.331
|
28.21 Percentage of days
Standard Deviation 34.768
|
32.82 Percentage of days
Standard Deviation 36.528
|
|
Percentages of Pain-free Days
Week 3
|
38.14 Percentage of days
Standard Deviation 38.113
|
32.45 Percentage of days
Standard Deviation 36.870
|
35.14 Percentage of days
Standard Deviation 37.688
|
|
Percentages of Pain-free Days
Week 4
|
35.52 Percentage of days
Standard Deviation 36.075
|
33.09 Percentage of days
Standard Deviation 38.059
|
—
|
|
Percentages of Pain-free Days
Week 5
|
36.04 Percentage of days
Standard Deviation 38.277
|
32.30 Percentage of days
Standard Deviation 35.303
|
—
|
|
Percentages of Pain-free Days
Week 6
|
39.97 Percentage of days
Standard Deviation 42.315
|
34.29 Percentage of days
Standard Deviation 37.358
|
—
|
|
Percentages of Pain-free Days
Week 3-6
|
36.87 Percentage of days
Standard Deviation 35.470
|
33.31 Percentage of days
Standard Deviation 32.875
|
—
|
SECONDARY outcome
Timeframe: Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)Population: Intent to Treat population.
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.
Outcome measures
| Measure |
GW876008 125 mg
n=117 Participants
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=119 Participants
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
n=112 Participants
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 6,No
|
84 Participants
|
88 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 1, Yes
|
15 Participants
|
14 Participants
|
16 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 6,Yes
|
33 Participants
|
29 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 5, No
|
76 Participants
|
81 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 1, Yes
|
28 Participants
|
28 Participants
|
33 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 1, No
|
89 Participants
|
87 Participants
|
76 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea,Week 2,Yes
|
30 Participants
|
30 Participants
|
32 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 2, No
|
87 Participants
|
86 Participants
|
80 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 3, Yes
|
34 Participants
|
33 Participants
|
29 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 3, No
|
83 Participants
|
85 Participants
|
83 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 4, Yes
|
32 Participants
|
31 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 4, No
|
85 Participants
|
86 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Diarrhea, Week 5, Yes
|
41 Participants
|
36 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 1 ,No
|
102 Participants
|
101 Participants
|
93 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 2, Yes
|
18 Participants
|
15 Participants
|
19 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 2, No
|
99 Participants
|
101 Participants
|
93 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 3, Yes
|
19 Participants
|
15 Participants
|
17 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 3, No
|
98 Participants
|
103 Participants
|
95 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 4, Yes
|
21 Participants
|
20 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 4, No
|
96 Participants
|
97 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 5, Yes
|
22 Participants
|
18 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 5, No
|
95 Participants
|
99 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 6, Yes
|
23 Participants
|
20 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Constipation, Week 6, No
|
94 Participants
|
97 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 1, Yes
|
21 Participants
|
19 Participants
|
22 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 1, No
|
96 Participants
|
96 Participants
|
87 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 2, Yes
|
24 Participants
|
23 Participants
|
24 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 2, No
|
93 Participants
|
93 Participants
|
88 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 3, Yes
|
27 Participants
|
25 Participants
|
21 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 3, No
|
90 Participants
|
93 Participants
|
91 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 4, Yes
|
26 Participants
|
29 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 4, No
|
91 Participants
|
88 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 5, Yes
|
31 Participants
|
30 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 5, No
|
86 Participants
|
87 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 6, Yes
|
34 Participants
|
27 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool frequency, Week 6, No
|
83 Participants
|
90 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 1, Yes
|
17 Participants
|
18 Participants
|
22 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 1, No
|
100 Participants
|
97 Participants
|
87 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 2, Yes
|
21 Participants
|
20 Participants
|
22 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 2, No
|
96 Participants
|
96 Participants
|
90 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 3, Yes
|
27 Participants
|
23 Participants
|
23 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 3, No
|
90 Participants
|
95 Participants
|
89 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 4, Yes
|
26 Participants
|
27 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 4, No
|
91 Participants
|
90 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 5, Yes
|
30 Participants
|
27 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 5, No
|
87 Participants
|
90 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 6, Yes
|
28 Participants
|
23 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Stool consistency, Week 6, No
|
89 Participants
|
94 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 1, Yes
|
24 Participants
|
17 Participants
|
22 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 1, No
|
93 Participants
|
98 Participants
|
87 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 2, Yes
|
24 Participants
|
26 Participants
|
27 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 2, No
|
93 Participants
|
90 Participants
|
85 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 3, Yes
|
30 Participants
|
31 Participants
|
24 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 3, No
|
87 Participants
|
87 Participants
|
88 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 4, Yes
|
28 Participants
|
28 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 4, No
|
89 Participants
|
89 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 5, Yes
|
27 Participants
|
29 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 5, No
|
90 Participants
|
88 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 6, Yes
|
29 Participants
|
28 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Sense of urgency, Week 6, No
|
88 Participants
|
89 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 1, Yes
|
19 Participants
|
14 Participants
|
17 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 1, No
|
98 Participants
|
101 Participants
|
92 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 2, Yes
|
22 Participants
|
14 Participants
|
18 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 2, No
|
95 Participants
|
102 Participants
|
94 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 3, Yes
|
19 Participants
|
19 Participants
|
19 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 3, No
|
98 Participants
|
99 Participants
|
93 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 4, Yes
|
23 Participants
|
20 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 4, No
|
94 Participants
|
97 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 5, Yes
|
21 Participants
|
15 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 5, No
|
96 Participants
|
102 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 6, Yes
|
23 Participants
|
20 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Bloating, Week 6, No
|
94 Participants
|
97 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 1, Yes
|
16 Participants
|
10 Participants
|
17 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 1, No
|
101 Participants
|
105 Participants
|
92 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 2, Yes
|
23 Participants
|
14 Participants
|
24 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 2, No
|
94 Participants
|
102 Participants
|
88 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 3, Yes
|
20 Participants
|
18 Participants
|
21 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 3, No
|
97 Participants
|
100 Participants
|
91 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 4, Yes
|
21 Participants
|
18 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 4, No
|
96 Participants
|
99 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 5, Yes
|
24 Participants
|
20 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 5, No
|
93 Participants
|
97 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 6, Yes
|
24 Participants
|
20 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Incomplete evacuation, Week 6, No
|
93 Participants
|
97 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 1, Yes
|
21 Participants
|
8 Participants
|
14 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 1, No
|
96 Participants
|
107 Participants
|
95 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 2, Yes
|
21 Participants
|
17 Participants
|
19 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 2, No
|
96 Participants
|
99 Participants
|
93 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 3, Yes
|
19 Participants
|
23 Participants
|
21 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 3, No
|
98 Participants
|
95 Participants
|
91 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 4, Yes
|
22 Participants
|
21 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 4, No
|
95 Participants
|
96 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 5, Yes
|
25 Participants
|
22 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 5, No
|
92 Participants
|
95 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 6, Yes
|
21 Participants
|
21 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
Straining, Week 6, No
|
96 Participants
|
96 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 1, Yes
|
29 Participants
|
22 Participants
|
30 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 1, No
|
88 Participants
|
93 Participants
|
79 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 2, Yes
|
42 Participants
|
22 Participants
|
30 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 2, No
|
75 Participants
|
94 Participants
|
82 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 3, Yes
|
37 Participants
|
30 Participants
|
29 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 3, No
|
80 Participants
|
88 Participants
|
83 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 4, Yes
|
37 Participants
|
33 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 4, No
|
80 Participants
|
84 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 5, Yes
|
35 Participants
|
30 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 5, No
|
82 Participants
|
87 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 6, Yes
|
41 Participants
|
29 Participants
|
0 Participants
|
|
Number of Participants With Improvements in Bowel Function and Changes in Individual Bowel Symptoms/Function
IBS symptoms, Week 6, No
|
76 Participants
|
88 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 measurementPopulation: Pharmacokinetic concentration population comprised of all participants for whom a pharmacokinetic sample was obtained and analyzed was included. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
GW876008 125 mg
n=107 Participants
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 3, pre dose
|
672.691 ng/mL
Standard Deviation 538.6495
|
—
|
—
|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 3, < 1 HR
|
NA ng/mL
Standard Deviation NA
Non Quantifiable
|
—
|
—
|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 3, 1 to < 2 HR
|
1312.573 ng/mL
Standard Deviation 716.2118
|
—
|
—
|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 3, >= 4 HR
|
696.690 ng/mL
Standard Deviation NA
1 participants was analyzed. thus S.D. was not calculated.
|
—
|
—
|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 6, pre dose
|
625.645 ng/mL
Standard Deviation 493.5978
|
—
|
—
|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 6, < 1 HR
|
850.028 ng/mL
Standard Deviation 680.8931
|
—
|
—
|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 6, 1 to < 2 HR
|
1082.773 ng/mL
Standard Deviation 656.4102
|
—
|
—
|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 6, 2 to < 3 HR
|
1004.535 ng/mL
Standard Deviation 642.8820
|
—
|
—
|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 3, 2 to < 3 HR
|
1170.096 ng/mL
Standard Deviation 873.3578
|
—
|
—
|
|
Plasma Concentrations of GW876008 at Week 3 and 6
Week 3, 3 to < 4 HR
|
966.653 ng/mL
Standard Deviation 528.0190
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)Investigation of possible composite symptom score was planned. The data was not collected for composite symptom score.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)Population: Intent to Treat population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
GW876008 125 mg
n=117 Participants
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=119 Participants
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
n=112 Participants
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Changes in Patient Health Questionnaire-15 Somatization Scale (PHQ-15) Score With Treatment
Week 3
|
8.6 Score on a scale
Standard Deviation 4.42
|
8.5 Score on a scale
Standard Deviation 3.89
|
8.5 Score on a scale
Standard Deviation 4.02
|
|
Changes in Patient Health Questionnaire-15 Somatization Scale (PHQ-15) Score With Treatment
Week 6
|
8.8 Score on a scale
Standard Deviation 4.99
|
8.5 Score on a scale
Standard Deviation 4.03
|
—
|
SECONDARY outcome
Timeframe: Up to Day 105 (weeks 3-6 in period 1, weeks 12-15 in period 2)Population: Intent to Treat population. Only those participants available at the specified time points were analyzed. Washout period was of 3 weeks only. Thus, these categories are not applicable for placebo washout arm.
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.
Outcome measures
| Measure |
GW876008 125 mg
n=112 Participants
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=117 Participants
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
n=111 Participants
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Summary of Anxiety and/or Depression on Hospital Anxiety and Depression Scale (HAD)
Anxiety, Week 3
|
4.84 Score on a scale
Standard Deviation 3.690
|
4.68 Score on a scale
Standard Deviation 3.845
|
4.61 Score on a scale
Standard Deviation 3.749
|
|
Summary of Anxiety and/or Depression on Hospital Anxiety and Depression Scale (HAD)
Anxiety, Week 6
|
4.98 Score on a scale
Standard Deviation 4.141
|
4.56 Score on a scale
Standard Deviation 3.630
|
—
|
|
Summary of Anxiety and/or Depression on Hospital Anxiety and Depression Scale (HAD)
Depression, Week 3
|
2.68 Score on a scale
Standard Deviation 3.027
|
2.79 Score on a scale
Standard Deviation 3.458
|
2.86 Score on a scale
Standard Deviation 3.297
|
|
Summary of Anxiety and/or Depression on Hospital Anxiety and Depression Scale (HAD)
Depression, Week 6
|
3.11 Score on a scale
Standard Deviation 3.612
|
2.50 Score on a scale
Standard Deviation 2.723
|
—
|
Adverse Events
GW876008 125 mg
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo Washout
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
GW876008 125 mg
n=119 participants at risk
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=120 participants at risk
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
n=112 participants at risk
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chondrosarcoma
|
0.00%
0/119 • Up to Day 147
Safety population was used for AE,SAE and nSAE collection.
|
0.83%
1/120 • Up to Day 147
Safety population was used for AE,SAE and nSAE collection.
|
0.00%
0/112 • Up to Day 147
Safety population was used for AE,SAE and nSAE collection.
|
Other adverse events
| Measure |
GW876008 125 mg
n=119 participants at risk
Eligible participants received GW876008 125 mg once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo
n=120 participants at risk
Eligible participants received matching placebo orally once daily for 6 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
Placebo Washout
n=112 participants at risk
Eligible participants received washout placebo orally once daily for 3 weeks. Participants were instructed to take 1 tablet from each of the 2 bottles; 25 mg and 100 mg orally in the morning with food. At the day of the Weeks 3, 6, 9, 12 and 15 Visit, participants were instructed not take their dose prior to their visit which was scheduled for the morning, they were instructed to take their dose at the site after collection of a pre-dose PK blood sample.
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
7.6%
9/119 • Up to Day 147
Safety population was used for AE,SAE and nSAE collection.
|
4.2%
5/120 • Up to Day 147
Safety population was used for AE,SAE and nSAE collection.
|
1.8%
2/112 • Up to Day 147
Safety population was used for AE,SAE and nSAE collection.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER