52-Week Efficacy and Safety Study of Ibodutant in Women With Irritable Bowel Syndrome With Diarrhea (IBS-D) (IRIS-4)

This is an interventional treatment trial for Irritable Bowel Syndrome With Diarrhea focused on measuring Irritable Bowel Syndrome, Colon, irritable, Bowel disease, Diarrhea Read More

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.