Irritable bowel syndrome with diarrhoea (IBS-D) in female patients. MedDRA version: 18.0 Level: LLT Classification code 10060849 Term: Diarrhoea predominant irritable bowel syndrome System Organ Class: 100000004856 MedDRA version: 18.0 Level: LLT Classification code 10060845 Term: Diarrhea predominant irritable bowel syndrome System Organ Class: 100000004856
Conditions
Sponsors
Menarini Ricerche S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Female patients aged 18 years or older. - Clinical diagnosis of IBS-D according to the following symptom-based criteria as per Rome III modular questionnaire criteria: - Recurrent abdominal pain or discomfort for at least 3 days per month in the last 3 months associated with at least 2 of the following characteristics: a) improvement with defecation; b) onset associated with a change in the frequency of stool; c) onset associated with a change in form (appearance) of stool. - Symptom-onset at least 6 months prior to diagnosis. - Loose or watery stools at least 25% of the time in the last 3 months AND hard or lumpy stools less than 25% of the time in the last 3 months. - Additional criterion: 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/flexible sigmoidoscopy performed within the last 5 years and after the onset of IBS symptoms, and completed before the start of the Screening period. - For patients aged 65 years or older: absence of ischaemic colitis, microscopic colitis, or any other organic gastrointestinal (GI) disease as evidenced by the results of a colonoscopy/ flexible sigmoidoscopy with biopsy performed within 6 months before the start of the Screening period. - Patient willing to refrain from using any anti-diarrhoeal loperamide within 3 days prior to the Run-in visit and during the Run-in period (to be re-checked prior to randomisation). At the end of Run in period, ONLY patients meeting the following e-diary criteria and all the other inclusion criteria will be eligible to progress to randomisation: - Patient has during both weeks of the Run-in period a weekly average of worst abdominal pain in the past 24 hours with a score of = 3.0 on a 0 to 10 point scale (Abdominal Pain Intensity). - Patient has during both weeks of the Run-in period at least one bowel movement on each day. - Patient has during both weeks of the Run-in period a weekly average of at least 3 bowel movements per day. - Patient has during both weeks of the Run-in period at least one stool with a consistency of Type 6 or Type 7 according to the Bristol Stool Scale (BSS) on at least 2 days per week (Stool Consistency). - Patient has during both weeks of the Run-in period less than 2 bowel movements with a consistency of Type 1 or Type 2 according to the BSS per week. - Adequate compliance with the e-diary recording procedure defined as at least 11 of 14 days (=75%) of the nominal daily entry considering the last consecutive 14 days prior the randomisation [NOTE: Run-in duration is 14 days (+3 days)]. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 450 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: NOTE: Patient with any alarm signs (e.g. fever, rectal bleeding other than haemorrhoids, unintentional weight loss, anaemia) deserve special consideration to exclude any organic GI disease. - Male gender. - Patient has a diagnosis of IBS with a subtype of constipation, mixed IBS, or unsubtyped IBS according to the Rome III criteria. - Patient has had surgery that meets any of the following criteria: a) Colonic or major abdominal surgery, i.e. bariatric surgery and stomach, small/large bowel or large vessel abdominal surgery (except appendicectomy, hysterectomy, cholecystectomy, caesarean section, or laparoscopic surgery). b) Any other major abdominal surgery in the previous 6 months. -Patient has any elective major surgery planned or expected at any time during the study. - Patient has a history of inflammatory bowel diseases, complicated diverticulosis (i.e. diverticulitis), ischaemic colitis, microscopic colitis. - Patient has a history of organic abnormalities of the GI tract, intestinal obstruction, stricture, toxic megacolon, GI perforation, faecal impaction, gastric banding, adhesions or impaired intestinal circulation (e.g. aortoiliac disease). - Patient has a history of pancreatitis of any aetiology, cholecystitis or of symptomatic gallbladder stone disease in the previous 6 months. - Patient has an active biliary duct disease or a history of Sphincter of Oddi dysfunction. - Patient has a history of gluten enteropathy. - Patient has a history of lactose intolerance as assessed by response to diet. - Patient has a current or previous diagnosis of neoplasia (except non-GI neoplasia in complete remission = 5 years, squamous and basal cell carcinomas and cervical carcinoma in situ). - Patient has a history of ectopic endometriosis. - Patient has a history of positive tests for ova or parasites, or clostridium difficile toxin or occult blood in the stool in the previous 6 months. - Relevant changes in dietary habits, lifestyle, or exercise regimen in the previous 2 months. NOTE: dietary habits, lifestyle and exercise regimen should be maintained for the duration of the study. - Use of prohibited concurrent medication within the previous month, namely: Antibiotics (4 months in the case of rifaximin); 5-HT3 antagonist alosetron. - Use of prohibited concurrent medication within the previous 7 days, namely (for details see protocol): Antimuscarinic drugs, Drugs enhancing GI motility, Analgesic drugs, Fibre products and herbal preparations, Antidepressants, Benzodiazepines
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ibodutant on IBS symptoms as compared to placebo in IBS-D female patients over a 24-week oral treatment period.;Secondary Objective: · To assess the safety and tolerability of ibodutant on 12, 24 and 52-week treatment course with oral 10 mg dose once daily in IBS-D female patients. · To evaluate the sustained effect of ibodutant on IBS symptoms in IBS-D female patients. · To evaluate ibodutant population pharmacokinetics in IBS-D female patients.;Primary end point(s): Primary Efficacy Endpoint: Weekly response for abdominal pain intensity AND stool consistency over the first 24 weeks of treatment in at least 50% of the weeks of treatment (12 out of 24 weeks). 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 past 24 hours of at least 30% compared with baseline (2-week Run-in period). NOTE: “Worst abdominal pain score in past 24 hours” hereafter will be called “abdominal pain intensity”. 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 (2-week Run-in period).;Timepoint(s) of evaluation of this end point: weekly response over 24 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Sustained efficacy evaluated as weekly response for abdominal pain intensity AND stool consistency over the first 24 weeks of treatment applying the 50% rule with at least 2 weeks in the last 4 weeks of treatment (weeks 21 to 24). The patient will be considered a weekly responder as defined in the primary endpoint. · Weekly response for abdominal pain intensity over the first 24 weeks of treatment in at least 50% of the weeks of treatment (12 out of 24 weeks). The patient will be considered a weekly responder as defined in the primary endpoint in terms of abdominal pain intensity. The same end-point will be evaluated over the first 12 weeks of treatment · Weekly response for stool consistency over the first 24 weeks of treatment in at least 50% of the weeks of treatment (12 out of 24 weeks). The patient will be considered a weekly responder as defined in the primary endpoint in terms of stool consistency. The same end-point will be evaluated over the first 12 weeks of treatment. · Weekly abdominal pain responder defined as a patient with a decrease of at least 30% versus baseline in the weekly average of abdominal pain intensity from randomisation until the end of first 24 weeks. Additionally the same endpoint will be considered with the thresholds of 40% and 50%. · Weekly stool consistency responder defined as a patient with a decrease versus baseline of at least 50% in the number of days per week with at least one stool that has the consistency of type 6 or 7 from randomisation until the end of first 24 weeks. Weekly Response for relief of IBS symptoms over the first 24 weeks of treatment in at least 50% of the weeks of treatment (12 out of 24 weeks). 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”. · Change in IBS-SSS from baseline after 12 and 24 weeks of the first treatment period. · Change of weekly average for each | — |
Countries
Czech Republic, Germany, Hungary, Latvia, Poland, Slovakia, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Research
Menarini Ricerche S.p.A.
Outcome results
None listed