Irritable Bowel Syndrome
Conditions
Keywords
Irritable Bowel Syndrome, Bowel disease
Brief summary
The purpose of the study is to evaluate the benefit of treatment with oral dose of Ibodutant (code: MEN 15596) on IBS symptoms and the safety and tolerability of this therapy.
Detailed description
Irritable Bowel Syndrome (IBS) is a functional disorder characterised by chronic or recurrent abdominal pain or discomfort associated with altered bowel habits. This trial aims to evaluate the efficacy of Ibodutant in improvement of IBS symptoms through a daily oral administration, testing three dosages or placebo in IBS patients for 4-weeks. In each patient, the experimental clinical phase encompasses a screening/ 2-week run-in period (no study medication), followed by a 4-weeks treatment period and a 2-weeks treatment withdrawal period, for total study duration of 8 weeks in each patient.
Interventions
DRUGIbodutant
Oral tablet, dose level 1 (10 mg), once daily
DRUGPlacebo
Oral tablet matching the three dose levels of ibodutant, once daily
Sponsors
Menarini Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged 18 - 70 years. 2. Clinical diagnosis of IBS . 3. For patients older than 50 years or patients with positive family history of colorectal cancer: normal results from colonoscopy or flexible sigmoidoscopy. 4. Use of appropriate contraceptive methods. 5. Normal physical examination or without clinically relevant abnormalities.
Exclusion criteria
1. Patients with organic abnormalities of the gastro-intestinal tract including history of colonic or major abdominal surgery, current or previous diagnosis of neoplasia, inflammatory bowel diseases, symptomatic gallbladder stone disease, diverticulosis/diverticulitis, ectopic endometriosis. 2. History of gluten enteropathy. 3. Lactose intolerance as assessed by response to diet 4. Diagnosis of ova or parasites, or occult blood in the stool in the previous 6 months. 5. Previous diagnosis of Diabetes Mellitus (either type 1 or 2) 6. Unstable medical condition. 7. Concomitant medication within 7 days prior to screening with drugs known to interfere with gastro-intestinal motility and sensitivity. 8. Pregnancy or breastfeeding. 9. Patient not able to understand or collaborate throughout the study. 10. Participation in other clinical trials in the previous 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response of Overall IBS Symptom Relief - 50% Rule | Four weeks | Weekly binary question (yes/no): Did you have satisfactory relief of your overall IBS symptoms since the last visit? Responder: report of satisfactory overall IBS symptom relief = Yes 2/4 weeks (50% rule) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response of Overall IBS Symptom Relief - 75% Rule | Four weeks | Weekly binary question (yes/no): Did you have satisfactory relief of your overall IBS symptoms since the last visit? Responder: report of satisfactory overall IBS symptom relief = Yes 3/4 weeks (75% rule) |
| Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS With Diarrhea (IBS-D) - 75% Rule | Four weeks | Weekly binary question (yes/no): Did you have satisfactory relief of your overall IBS symptoms since the last visit? Responder: report of satisfactory overall IBS symptom relief = Yes 3/4 weeks (75% rule) |
Countries
Denmark, Germany, Latvia, Russia, Ukraine, United Kingdom
Participant flow
Recruitment details
First subject enrolled 15/07/2008, last subject observed 18/02/2009, at 60 study centres in 9 European countries (Denmark, Germany, Italy, Latvia, Russia, Slovak Republic, Spain, United Kingdom, and Ukraine.
Pre-assignment details
Subjects underwent a 2-week screening period to meet inclusion/exclusion criteria and were subsequently randomised.
Participants by arm
| Arm | Count |
|---|---|
| Ibodutant 10 mg oral tablet, once daily | 140 |
| Ibodutant 30 mg oral tablet, once daily | 133 |
| Ibodutant 60 mg oral tablet, once daily | 135 |
| Placebo oral tablet, once daily | 136 |
| Total | 544 |
Baseline characteristics
| Characteristic | Ibodutant 10 mg | Ibodutant 30 mg | Ibodutant 60 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous | 43.9 years STANDARD_DEVIATION 13.43 | 45.0 years STANDARD_DEVIATION 12.66 | 44.4 years STANDARD_DEVIATION 12.97 | 43.7 years STANDARD_DEVIATION 13.73 | 44.2 years STANDARD_DEVIATION 13.18 |
| IBS-Subtype IBS-Constipation | 37 participants | 44 participants | 34 participants | 50 participants | 165 participants |
| IBS-Subtype IBS-Diarrhea | 68 participants | 53 participants | 59 participants | 54 participants | 234 participants |
| IBS-Subtype IBS-Mixed | 26 participants | 29 participants | 34 participants | 22 participants | 111 participants |
| IBS-Subtype IBS-Unsubtyped | 9 participants | 7 participants | 8 participants | 10 participants | 34 participants |
| Sex: Female, Male Female | 104 Participants | 79 Participants | 90 Participants | 94 Participants | 367 Participants |
| Sex: Female, Male Male | 36 Participants | 54 Participants | 45 Participants | 42 Participants | 177 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 29 / 140 | 29 / 135 | 28 / 139 | 26 / 137 |
| serious Total, serious adverse events | 0 / 140 | 3 / 135 | 1 / 139 | 0 / 137 |
Outcome results
Primary
Response of Overall IBS Symptom Relief - 50% Rule
Weekly binary question (yes/no): Did you have satisfactory relief of your overall IBS symptoms since the last visit? Responder: report of satisfactory overall IBS symptom relief = Yes 2/4 weeks (50% rule)
Time frame: Four weeks
Population: Intention-to-Treat (N=544)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibodutant 10 mg | Response of Overall IBS Symptom Relief - 50% Rule | 79 Participants |
| Ibodutant 30 mg | Response of Overall IBS Symptom Relief - 50% Rule | 61 Participants |
| Ibodutant 60 mg | Response of Overall IBS Symptom Relief - 50% Rule | 61 Participants |
| Placebo | Response of Overall IBS Symptom Relief - 50% Rule | 78 Participants |
Secondary
Response of Overall IBS Symptom Relief - 75% Rule
Weekly binary question (yes/no): Did you have satisfactory relief of your overall IBS symptoms since the last visit? Responder: report of satisfactory overall IBS symptom relief = Yes 3/4 weeks (75% rule)
Time frame: Four weeks
Population: Intention-to-Treat (N=544)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibodutant 10 mg | Response of Overall IBS Symptom Relief - 75% Rule | 53 Participants |
| Ibodutant 30 mg | Response of Overall IBS Symptom Relief - 75% Rule | 39 Participants |
| Ibodutant 60 mg | Response of Overall IBS Symptom Relief - 75% Rule | 37 Participants |
| Placebo | Response of Overall IBS Symptom Relief - 75% Rule | 48 Participants |
Secondary
Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS With Diarrhea (IBS-D) - 75% Rule
Weekly binary question (yes/no): Did you have satisfactory relief of your overall IBS symptoms since the last visit? Responder: report of satisfactory overall IBS symptom relief = Yes 3/4 weeks (75% rule)
Time frame: Four weeks
Population: Intention-to-treat (ITT) subgroup of patients with IBS-D (N=234)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibodutant 10 mg | Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS With Diarrhea (IBS-D) - 75% Rule | 33 Participants |
| Ibodutant 30 mg | Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS With Diarrhea (IBS-D) - 75% Rule | 17 Participants |
| Ibodutant 60 mg | Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS With Diarrhea (IBS-D) - 75% Rule | 22 Participants |
| Placebo | Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS With Diarrhea (IBS-D) - 75% Rule | 25 Participants |
Post Hoc
Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS-Diarrhea (IBS-D) and Pain at Baseline - 75% Rule
Weekly binary question (yes/no): Did you have satisfactory relief of your overall IBS symptoms since the last visit? Responder: report of satisfactory overall IBS symptom relief = Yes 3/4 weeks (75% rule)
Time frame: Four weeks
Population: Intention-to-treat subgroup of patients with IBS-D and baseline pain score\>1 (in a 5-point scale ranging from 0=no pain to 4=very severe) (N=189)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibodutant 10 mg | Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS-Diarrhea (IBS-D) and Pain at Baseline - 75% Rule | 31 Participants |
| Ibodutant 30 mg | Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS-Diarrhea (IBS-D) and Pain at Baseline - 75% Rule | 15 Participants |
| Ibodutant 60 mg | Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS-Diarrhea (IBS-D) and Pain at Baseline - 75% Rule | 17 Participants |
| Placebo | Response of Overall IBS Symptom Relief in the Subgroup of Patients With IBS-Diarrhea (IBS-D) and Pain at Baseline - 75% Rule | 19 Participants |