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 symptoms-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 a 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, microscopy 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 is willing to refrain from using any anti-diarrhoeal loperamide within 3 days prior to 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 data 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: Patients 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, fecal impaction, gastric banding, adhesions or impaired intestinal circulation (e.g., aortoiliac disease). - Patient has a history of pancreatitis of any etiology, 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 in the previous 7 days namely (see protocol for details): Antimuscarinic drugs; Drugs enhancing GI motility such as prokinetic agents and other stimulants of GI contractility drugs, laxatives, or anti-diarrhoeal agents (except for loperamide, please refer to inclusion criterion No.12); Analgesic drugs (opioids or non-steroidal anti-inflammatory drugs). NOTE: short term use of paracetamol is allowed for max 2 consecutive days; 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 12 week oral treatment period. ;Secondary Objective: • To assess the safety and tolerability of ibodutant on 12 and 16-week treatment course with oral 10 mg dose once daily in IBS-D female patients. • To evaluate the rebound effect on IBS symptoms in IBS-D female patients after treatment discontinuation. • 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 12 weeks of treatment in at least 50% of the weeks of treatment (6 out of 12 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 the past 24 hours of at least 30% compared with baseline (2-week Run-in period); NOTE: “Worst abdominal pain score in the 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 12 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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). The patient will be considered a weekly responder as defined in the primary endpoint in terms of abdominal pain intensity. • Weekly response for stool consistency over 12 weeks of treatment in at least 50% of the weeks of treatment (6 out of 12 weeks). The patient will be considered a weekly responder as defined in the primary endpoint in terms of stool consistency. • Weekly abdominal pain responder, defined as a patient with a decrease versus baseline (2-week Run-in period) of at least 30 % in the weekly average of abdominal pain intensity from Randomisation until the end of week 12. 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 (2-week Run-in period) 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 from Randomisation until the end of week 12. • 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). 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”. • Evaluation of rebound effect by comparison between average abdominal pain intensity and stool consistency during the 4-week RW treatment period and baseline (2-week Run-in period) in patients who are re-randomised to placebo after being treated with ibodutant. • Change in IBS-SSS from baseline (Visit 3) after 12-week double-blind treatment period and 4-week RW treatment period. • Change of weekly average for each week during the 12-week double-blind treatment period and the 4-week RW treatment period versus baseline (2-week Run-in period) of specific symptoms o | — |
Countries
Bulgaria, Czech Republic, France, Germany, Italy, Poland, Romania, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactClinical Research
Menarini Ricerche S.p.A.
Outcome results
None listed