Trial Outcomes & Findings for 12-Week Efficacy and Safety Study of Ibodutant in Women With Irritable Bowel Syndrome With Diarrhea (IBS-D) (NCT NCT02107196)
NCT ID: NCT02107196
Last Updated: 2017-01-19
Results Overview
The patient will be considered a weekly responder if she meets both of the following criteria in the same week: * Abdominal pain response: decrease in weekly average of worst abdominal pain score in the past 24 hours of at least 30% compared with baseline; * Stool consistency response: decrease of at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline. The patients reported Bristol Stoll Chart score based on a 1 to 7 scale where 1 corresponds to hard stool and 7 corresponds to watery diarrhoea.
COMPLETED
PHASE3
535 participants
12 weeks
2017-01-19
Participant Flow
The first patient was screened on 27th February 2014 and the first patient randomized on 21st March 2014. The last patient completed the study on 22nd June 2015. The study was conducted at 158 clinical sites in 11 countries (Bulgaria, Czech Republic, France, Germany, Italy, Poland, Romania, Russia, Spain, the USA and the United Kingdom).
A total of 1237 patients entered a 2-week Screening period, 1034 entered the qualifying 2-week Run-in period and 535 of them were randomised. After completion of the double-blind 12-week treatment, 453 patients entered into the Randomised Withdrawal (RW) period.
Participant milestones
| Measure |
Ibodutant 10 mg
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomized to the ibodutant 10 mg arm will be re-randomized at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomized to the placebo arm will be mock-re-randomized (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
|---|---|---|
|
12-week Treatment Period
STARTED
|
271
|
264
|
|
12-week Treatment Period
Intention To Treat (ITT)
|
271
|
264
|
|
12-week Treatment Period
Modified ITT
|
221
|
216
|
|
12-week Treatment Period
COMPLETED
|
227
|
225
|
|
12-week Treatment Period
NOT COMPLETED
|
44
|
39
|
|
4-week Randomized Withdrawal (RW) Period
STARTED
|
338
|
114
|
|
4-week Randomized Withdrawal (RW) Period
RW Population
|
338
|
114
|
|
4-week Randomized Withdrawal (RW) Period
Modified RW Population
|
272
|
90
|
|
4-week Randomized Withdrawal (RW) Period
COMPLETED
|
315
|
109
|
|
4-week Randomized Withdrawal (RW) Period
NOT COMPLETED
|
23
|
5
|
Reasons for withdrawal
| Measure |
Ibodutant 10 mg
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomized to the ibodutant 10 mg arm will be re-randomized at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomized to the placebo arm will be mock-re-randomized (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
|---|---|---|
|
12-week Treatment Period
Adverse Event
|
6
|
3
|
|
12-week Treatment Period
Lack of Efficacy
|
2
|
1
|
|
12-week Treatment Period
Lost to Follow-up
|
3
|
6
|
|
12-week Treatment Period
Physician Decision
|
0
|
1
|
|
12-week Treatment Period
Withdrawal by Subject
|
15
|
12
|
|
12-week Treatment Period
Protocol Violation
|
7
|
8
|
|
12-week Treatment Period
Reason Missing
|
11
|
8
|
|
4-week Randomized Withdrawal (RW) Period
Adverse Event
|
2
|
0
|
|
4-week Randomized Withdrawal (RW) Period
Withdrawal by Subject
|
1
|
0
|
|
4-week Randomized Withdrawal (RW) Period
Protocol Violation
|
2
|
0
|
|
4-week Randomized Withdrawal (RW) Period
Reason Missing
|
18
|
5
|
Baseline Characteristics
12-Week Efficacy and Safety Study of Ibodutant in Women With Irritable Bowel Syndrome With Diarrhea (IBS-D)
Baseline characteristics by cohort
| Measure |
Ibodutant 10 mg
n=271 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will be re-randomised at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
n=264 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the placebo arm will be mock-re-randomised (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
Total
n=535 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42.5 years
STANDARD_DEVIATION 12.81 • n=99 Participants
|
43.8 years
STANDARD_DEVIATION 12.47 • n=107 Participants
|
43.1 years
STANDARD_DEVIATION 12.65 • n=206 Participants
|
|
Gender
Female
|
271 Participants
n=99 Participants
|
264 Participants
n=107 Participants
|
535 Participants
n=206 Participants
|
|
Gender
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
149 participants
n=99 Participants
|
136 participants
n=107 Participants
|
285 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
122 participants
n=99 Participants
|
128 participants
n=107 Participants
|
250 participants
n=206 Participants
|
|
Region of Enrollment
North America
|
202 participants
n=99 Participants
|
198 participants
n=107 Participants
|
400 participants
n=206 Participants
|
|
Region of Enrollment
Europe
|
69 participants
n=99 Participants
|
66 participants
n=107 Participants
|
135 participants
n=206 Participants
|
|
Abdominal Pain Severity Score
<5
|
46 participants
n=99 Participants
|
37 participants
n=107 Participants
|
83 participants
n=206 Participants
|
|
Abdominal Pain Severity Score
>=5 to <8
|
176 participants
n=99 Participants
|
187 participants
n=107 Participants
|
363 participants
n=206 Participants
|
|
Abdominal Pain Severity Score
>=8
|
49 participants
n=99 Participants
|
40 participants
n=107 Participants
|
89 participants
n=206 Participants
|
|
IBS-SSS Score
Mild IBS (<175)
|
2 participants
n=99 Participants
|
6 participants
n=107 Participants
|
8 participants
n=206 Participants
|
|
IBS-SSS Score
Moderate IBS (175 to <300)
|
35 participants
n=99 Participants
|
44 participants
n=107 Participants
|
79 participants
n=206 Participants
|
|
IBS-SSS Score
Severe IBS (>=300)
|
233 participants
n=99 Participants
|
212 participants
n=107 Participants
|
445 participants
n=206 Participants
|
|
IBS-SSS Score
Missing
|
1 participants
n=99 Participants
|
2 participants
n=107 Participants
|
3 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: The primary efficacy analysis was performed on the modified ITT population (n=437): all patients included in the ITT population excluding patients from one site, where a potential serious breach of GCP was reported, and from another site, where disqualification proceedings against the Investigator were confirmed by the FDA.
The patient will be considered a weekly responder if she meets both of the following criteria in the same week: * Abdominal pain response: decrease in weekly average of worst abdominal pain score in the past 24 hours of at least 30% compared with baseline; * Stool consistency response: decrease of at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline. The patients reported Bristol Stoll Chart score based on a 1 to 7 scale where 1 corresponds to hard stool and 7 corresponds to watery diarrhoea.
Outcome measures
| Measure |
Ibodutant 10 mg
n=221 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will be re-randomised at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
n=216 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the placebo arm will be mock-re-randomised (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
|---|---|---|
|
Weekly Response for Abdominal Pain Intensity AND Stool Consistency Over 12 Weeks of Treatment in at Least 50% of the Weeks of Treatment (6 Out of 12 Weeks).
|
35.7 Percentage of Responders
|
34.7 Percentage of Responders
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The secondary efficacy analysis was performed on the modified ITT population (n=437): all patients included in the ITT population excluding patients from one site, where a potential serious breach of GCP was reported, and from another site, where disqualification proceedings against the Investigator were confirmed by the FDA.
The patient will be considered a weekly abdominal pain responder if she meets the following criterion: * Decrease in weekly average of worst abdominal pain score in the past 24 hours of at least 30% compared with baseline.
Outcome measures
| Measure |
Ibodutant 10 mg
n=221 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will be re-randomised at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
n=216 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the placebo arm will be mock-re-randomised (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
|---|---|---|
|
Weekly Response for Abdominal Pain Intensity Over 12 Weeks of Treatment in at Least 50% of the Weeks of Treatment (6 Out of 12 Weeks).
|
48.0 percentage of responders
|
47.7 percentage of responders
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The secondary efficacy analysis was performed on the modified ITT population (n=437): all patients included in the ITT population excluding patients from one site, where a potential serious breach of GCP was reported, and from another site, where disqualification proceedings against the Investigator were confirmed by the FDA.
The patient will be considered a weekly stool consistency responder if she meets the following criterion: * Decrease of at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline. The patients reported Bristol Stool Chart score based on a 1 to 7 scale where 1 corresponds to hard stool and 7 corresponds to watery diarrhoea.
Outcome measures
| Measure |
Ibodutant 10 mg
n=221 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will be re-randomised at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
n=216 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the placebo arm will be mock-re-randomised (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
|---|---|---|
|
Weekly Response for Stool Consistency Over 12 Weeks of Treatment in at Least 50% of the Weeks of Treatment (6 Out of 12 Weeks).
|
44.8 percentage of responders
|
43.1 percentage of responders
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The secondary efficacy analysis was performed on the modified ITT population (n=437): all patients included in the ITT population excluding patients from one site, where a potential serious breach of GCP was reported, and from another site, where disqualification proceedings against the Investigator were confirmed by the FDA.
The patient will be considered a weekly responder if she has an IBS degree-of-relief equal to "completely relieved/improved" or "considerably relieved/improved".
Outcome measures
| Measure |
Ibodutant 10 mg
n=221 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will be re-randomised at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
n=216 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the placebo arm will be mock-re-randomised (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
|---|---|---|
|
Weekly Response for Relief of Overall IBS Signs and Symptoms Over 12 Weeks of Treatment in at Least 50% of the Weeks of Treatment (6 Out of 12 Weeks).
|
21.3 percentage of responders
|
19.0 percentage of responders
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: modified RW population: only patients randomised to ibodutant in the 12-week treatment period and re-randomized to placebo for the 4-week RW period (excluding patients from one site, where a potential serious breach of GCP was reported, and another site, where disqualification proceedings against the Investigator were confirmed by FDA).
Comparison between average abdominal pain intensity (worst abdominal pain on a 0 to 10 NRS scale, where 0 corresponds to no pain and 10 corresponds to worst possible pain) and average stool consistency score (the patients reported Bristol Stool Chart score based on a 1 to 7 NRS scale where 1 corresponds to hard stool and 7 corresponds to watery diarrhoea) during the 4-week RW presented as change to baseline. The analysis only included the patients randomised to ibodutant in the 12-week treatment period and re-randomised to placebo for the 4-week RW period. Baseline was considered as the average abdominal pain intensity/stool consistency in the 2-week Run-in period.
Outcome measures
| Measure |
Ibodutant 10 mg
n=89 Participants
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will be re-randomised at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the placebo arm will be mock-re-randomised (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
|---|---|---|
|
Evaluation of Rebound Effects
Baseline-Abdominal Pain Score (NRS, 0-10 points)
|
6.53 units on a scale
Standard Deviation 1.60
|
—
|
|
Evaluation of Rebound Effects
4-week RW-Abdominal Pain Score (NRS, 0-10 points)
|
-3.11 units on a scale
Standard Deviation 2.21
|
—
|
|
Evaluation of Rebound Effects
Baseline-Bristol Stool Scale (NRS, 1 - 7 points)
|
6.05 units on a scale
Standard Deviation 0.52
|
—
|
|
Evaluation of Rebound Effects
4-week RW-Bristol Stool Scale (NRS, 1 - 7 points)
|
-1.38 units on a scale
Standard Deviation 1.37
|
—
|
Adverse Events
Ibodutant 10 mg
Placebo
Serious adverse events
| Measure |
Ibodutant 10 mg
n=271 participants at risk
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will be re-randomised at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
n=264 participants at risk
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the placebo arm will be mock-re-randomised (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/271 • 12-week double blind treatment period
|
0.38%
1/264 • Number of events 1 • 12-week double blind treatment period
|
|
Vascular disorders
Circulatory Collaps
|
0.00%
0/271 • 12-week double blind treatment period
|
0.38%
1/264 • Number of events 1 • 12-week double blind treatment period
|
Other adverse events
| Measure |
Ibodutant 10 mg
n=271 participants at risk
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will be re-randomised at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.
Ibodutant 10 mg: Oral tablet, to be given once daily.
|
Placebo
n=264 participants at risk
Oral tablet to be given once daily for 12 weeks of treatment. Patients randomised to the placebo arm will be mock-re-randomised (switch in blinded conditions) to ibodutant at week 13 for additional 4 weeks of treatment.
Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.1%
3/271 • Number of events 3 • 12-week double blind treatment period
|
0.00%
0/264 • 12-week double blind treatment period
|
|
Gastrointestinal disorders
Nausea
|
1.1%
3/271 • Number of events 3 • 12-week double blind treatment period
|
0.38%
1/264 • Number of events 1 • 12-week double blind treatment period
|
|
Infections and infestations
Gastroenteritis
|
0.37%
1/271 • Number of events 1 • 12-week double blind treatment period
|
1.1%
3/264 • Number of events 3 • 12-week double blind treatment period
|
|
Infections and infestations
Nasopharyngitis
|
2.6%
7/271 • Number of events 7 • 12-week double blind treatment period
|
2.3%
6/264 • Number of events 6 • 12-week double blind treatment period
|
|
Infections and infestations
Urinary tract infections
|
3.0%
8/271 • Number of events 8 • 12-week double blind treatment period
|
2.7%
7/264 • Number of events 8 • 12-week double blind treatment period
|
|
Investigations
Gamma-glutamyltransferase increased
|
1.1%
3/271 • Number of events 3 • 12-week double blind treatment period
|
0.00%
0/264 • 12-week double blind treatment period
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.37%
1/271 • Number of events 1 • 12-week double blind treatment period
|
1.5%
4/264 • Number of events 4 • 12-week double blind treatment period
|
|
Musculoskeletal and connective tissue disorders
muscle spasm
|
1.1%
3/271 • Number of events 3 • 12-week double blind treatment period
|
0.38%
1/264 • Number of events 1 • 12-week double blind treatment period
|
|
Nervous system disorders
Headache
|
1.1%
3/271 • Number of events 3 • 12-week double blind treatment period
|
3.8%
10/264 • Number of events 11 • 12-week double blind treatment period
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.1%
3/271 • Number of events 3 • 12-week double blind treatment period
|
0.38%
1/264 • Number of events 1 • 12-week double blind treatment period
|
Additional Information
Angela Capriati, MD PhD - Corporate Director Clinical Research
MENARINI Group
Results disclosure agreements
- Principal investigator is a sponsor employee Prior to submitting the results of this study for publication or presentation, the Investigator will allow the sponsor at least 30 days time to review and comment upon the publication manuscript. It is agreed, that the results of the study will not be submitted for presentation, abstract, poster exhibition, or publication by the investigator until Menarini Ricerche S.p.A. has reviewed/commented and agreed to any publication.
- Publication restrictions are in place
Restriction type: OTHER