Clinical trial NCT02107196 (phase 3, status: completed)
Conditions: irritable bowel syndrome with diarrhea
ICD codes: K58.0, K58.9
Drugs: ibodutant 10 mg, placebo
SMILES: CC1=CC=C2C=C(SC2=C1)C(=O)NC1(CCCC1)C(=O)N[C@H](CC1=CC=CC=C1)C(=O)NCC1CCN(CC2CCOCC2)CC1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
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.

          -  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.