52-Week Efficacy and Safety Study of Ibodutant in Women With Irritable Bowel Syndrome With Diarrhea (IBS-D)
Condition: Irritable Bowel Syndrome With Diarrhea
MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea
Intervention: Ibodutant 10 mg; Placebo
Intervention description: Oral tablet, to be given once daily.; Oral tablet (identical in appearance and weight to ibodutant tablets) to be given once daily.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 558.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Irritable Bowel Syndrome; Colon, irritable; Bowel disease; Diarrhea

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 oral ibodutant 10 mg once daily as
      compared to placebo in women with IBS-D over a 24-week treatment period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At screening:

               -  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:

                    1. 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.

                    2. Symptom-onset at least 6 months prior to diagnosis.

                    3. 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.

                    4. 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.

               -  For patients aged 65 years or older: absence of ischaemic colitis, microscopy
                  colitis or any other organic gastrointestinal disease as evidenced by the results
                  of a colonoscopy/flexible sigmoidoscopy with biopsy performed within 6 months.

               -  For women of childbearing potential: Use of a highly effective contraceptive
                  method with a failure rate <1% per year throughout the entire study period.

               -  Physical examination without clinically relevant abnormalities during screening.

               -  No clinically relevant abnormalities in 12-Lead ECG or in laboratory findings.

               -  Mentally competent, able to give written informed consent, and compliant to
                  undergo all visits and procedures.

               -  Unrestricted access to a touch-tone telephone.

               -  Willingness to refrain from using loperamide within 3 days prior to run-in visit
                  and during the run-in period.

        Additional criteria at randomisation:

          -  During both weeks of the run-in period:

               1. 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.

               2. At least one bowel movement on each day.

               3. A weekly average of at least 3 bowel movements per day.

               4. 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.

               5. Less than 2 bowel movements with a consistency of Type 1 or Type 2 according to
                  the BSS per week.

               6. Adequate compliance with the e-diary recording procedure defined as at least 11
                  of 14 days (≥75%) of the nominal daily data entry.

                  Exclusion Criteria:

          -  Male gender.

          -  Diagnosis of IBS with a subtype of constipation, mixed IBS, or un-subtyped IBS.

          -  Colonic or major abdominal surgery, any other major abdominal surgery or elective
             major surgery planned or expected during the study.

          -  History of organic GI abnormalities, inflammatory bowel diseases, complicated
             diverticulosis, ischaemic colitis, microscopic colitis.

          -  History of pancreatitis, active biliary duct disease, cholecystitis or symptomatic
             gallbladder stone disease in the previous 6 months.

          -  History of gluten enteropathy or lactose intolerance.

          -  Current or previous diagnosis of neoplasia.

          -  History of endometriosis.

          -  History of positive tests for ova or parasites, or clostridium difficile toxin or
             occult blood in the stool in the previous 6 months.

          -  History of human immunodeficiency virus infection.

          -  History of major cardiovascular events in the previous 6 months.

          -  Uncontrolled hypertension, insulin-dependent diabetes mellitus or abnormal thyroid
             function.

          -  Major psychiatric or neurological disorders or unstable medical condition which may
             compromise the efficacy and safety assessments.

          -  Evidence of clinically significant hepatic disease, severe renal insufficiency or
             anemia.

          -  Relevant changes in dietary habits, lifestyle, or exercise regimen in the previous 2
             months.

          -  Use of prohibited concurrent medication within the previous month such as antibiotics,
             antimuscarinic drugs, drugs enhancing GI motility and analgesics.

          -  Pregnancy or breastfeeding.

          -  Inability to understand or collaborate throughout the study.

          -  Participation in other clinical studies in the previous 4 weeks or concurrent
             enrollment in a clinical study.

          -  Any condition that would compromise the well-being of the patient.