Ibodutant for Relief of Irritable Bowel Syndrome With Diarrhoea (IBS-D)

Study Overview
=================
Brief Summary
-----------------
Irritable Bowel Syndrome with diarrhoea (IBS-D) is a functional gastrointestinal disorder characterised by chronic or recurrent abdominal pain or discomfort and diarrhoea. This trial aims at the evaluation of the efficacy and safety of the neurokinin type 2 receptor antagonist Ibodutant in improving IBS-D symptoms.

Detailed Description
-----------------
The study evaluates the efficacy and safety of three doses of ibodutant, given once daily for 8 weeks versus placebo in IBS-D patients. Efficacy is evaluated in terms of overall symptom relief and abdominal pain/discomfort relief after 8 weeks of treatment. The clinical phase of the study comprises a 2-week run-in period (treatment-free),an 8-week double-blind treatment period and a 2-week treatment withdrawal period, resulting in a 10-week overall duration of the study for each patient. Patients report their IBS-related symptoms daily in an electronic diary (web-and telephone based)during all periods of the study.

Official Title
-----------------
Double-blind, Randomised, Placebo-controlled, Parallel-group Phase II Study to Evaluate the Effect of Oral Ibodutant in Irritable Bowel Syndrome With Diarrhoea (IBS-D).

Conditions
-----------------
Irritable Bowel Syndrome With Diarrhea

Intervention / Treatment
-----------------
* Drug: Ibodutant
* Drug: Ibodutant
* Drug: Ibodutant
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At start of the run-in period: Male or female patients aged 18 - 70 years with a clinical diagnosis of IBS-D according to the Rome III criteria: Recurrent abdominal pain/discomfort for at least 3 days per month in the last 3 months associated with at least 2 of the following characteristics: improvement with defecation; onset associated with a change in the frequency of stool; onset associated with a change in form (appearance) of stool. Symptom-onset at least 6 months prior to diagnosis. Loose/watery stools at least 25% of the time in the last 3 months AND hard/lumpy stools less than 25% of the time in the last 3 months. More than 3 bowel movements per day at least 25% of the time in the last 3 months. For patients older than 50 years OR patients with positive family history of colorectal cancer: Normal results from colonoscopy or flexible sigmoidoscopy. Mentally competent, able to give written informed consent. For women of childbearing potential: Use of a highly effective contraceptive method throughout the entire study period and up to 30 days post-treatment. Normal physical examination or without clinically relevant abnormalities. At randomisation: -Confirmation of IBS-D severity in terms of bowel movement frequency and abdominal pain intensity along the 2-week run-in period. Exclusion criteria: Organic abnormalities of the gastrointestinal tract, including history of colonic or major abdominal surgery. History of gluten enteropathy. Lactose intolerance as assessed by response to diet. History of positive tests for ova or parasites, or occult blood in the stool. Previous diagnosis of diabetes mellitus (either type 1 or 2). Unstable medical condition. Major psychiatric, neurological, or cardiovascular disorders, or uncontrolled metabolic disease. Relevant changes in dietary habits, lifestyle, or exercise regimen in the previous 2 months. Use of concurrent medication with drugs known to interfere with gastro-intestinal motility or sensitivity. Pregnancy or breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibodutant low dose<br>Oral tablet, to be given once daily in fasting conditions. | Drug: Ibodutant<br>* Oral tablet, low dose, once daily, for 8 weeks<br>* Other names: Code: MEN 15596;|
| Experimental: Ibodutant intermediate dose<br>Oral tablet, to be given once daily in fasting conditions. | Drug: Ibodutant<br>* Oral tablet, intermediate dose, once daily, for 8 weeks<br>* Other names: Code: MEN 15596;|
| Experimental: Ibodutant high dose<br>Oral tablet, to be given once daily in fasting conditions. | Drug: Ibodutant<br>* Oral tablet, high dose, once daily, for 8 weeks<br>* Other names: Code: MEN 15569;|
| Placebo Comparator: Placebo<br>Oral tablet, to be given once daily in fasting conditions. | Drug: Placebo<br>* Oral tablet, (identical in appearance and weight to Ibodutant tablets), once daily, for 8 weeks<br>* Other names: Sugar pill;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 6 Weeks With Satisfactory Relief During 8 Weeks of Treatment (75% Rule); Intention-to-treat (ITT). | Weekly binary questions (yes/no) from Interactive Voice/Web Response (IV/WRS) diary records: Did you have satisfactory relief of your overall IBS symptoms during the last week? and Did you have satisfactory relief of your abdominal pain or discomfort during the last week? Responder: Report of satisfactory overall IBS symptom relief =Yes and of satisfactory abdominal pain/discomfort relief = Yes 6/8 weeks (75% rule) | Eight weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 4 Weeks With Satisfactory Relief During 8 Weeks of Treatment (50% Rule) in the ITT Population | Weekly binary questions (yes/no) from IV/WRS diary records: Did you have satisfactory relief of your overall IBS symptoms during the last week? and Did you have satisfactory relief of your abdominal pain or discomfort during the last week? Responder: Report of satisfactory overall IBS symptom relief =Yes and of satisfactory abdominal pain/discomfort relief = Yes 4/8 weeks with at least 2 consecutive weeks of satisfactory relief during Week 5 to Week 8(50% rule) | Eight weeks | 
| Quality of Life Changes (Using EuroQoL EQ-5D Questionnaire) | Change in EQ-5D Quality of Life (visual analogue scale) score at the end of 8 weeks of treatment versus baseline (at randomisation). EQ-5D quality of life visual analogue scale ranges from 0= worst imaginable health state to 100=best imaginable health state. | Eight weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Irritable Bowel Syndrome, Colon, irritable, Bowel disease