Ibodutant for Relief of Irritable Bowel Syndrome With Diarrhoea (IBS-D)

Double-blind, Randomised, Placebo-controlled, Parallel-group Phase II Study to Evaluate the Effect of Oral Ibodutant in Irritable Bowel Syndrome With Diarrhoea (IBS-D).

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 the neurokinin type 2 receptor antagonist Ibodutant in improving IBS-D symptoms.

The study evaluates the efficacy and safety of three doses of ibodutant, given once daily for 8 weeks versus placebo in IBS-D patients. Efficacy is evaluated in terms of overall symptom relief and abdominal pain/discomfort relief after 8 weeks of treatment. The clinical phase of the study comprises a 2-week run-in period (treatment-free),an 8-week double-blind treatment period and a 2-week treatment withdrawal period, resulting in a 10-week overall duration of the study for each patient.

Patients report their IBS-related symptoms daily in an electronic diary (web-and telephone based)during all periods of the study.

Inclusion Criteria:

At start of the run-in period:

• Male or female patients aged 18 - 70 years with a clinical diagnosis of IBS-D according to the Rome III criteria:

• Recurrent abdominal pain/discomfort for at least 3 days per month in the last 3 months associated with at least 2 of the following characteristics:

  1. improvement with defecation;
  2. onset associated with a change in the frequency of stool;
  3. onset associated with a change in form (appearance) of stool.

• Symptom-onset at least 6 months prior to diagnosis.

• Loose/watery stools at least 25% of the time in the last 3 months AND hard/lumpy stools less than 25% of the time in the last 3 months.

• 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 or flexible sigmoidoscopy.

• Mentally competent, able to give written informed consent.

• For women of childbearing potential: Use of a highly effective contraceptive method throughout the entire study period and up to 30 days post-treatment.

• Normal physical examination or without clinically relevant abnormalities.

At randomisation:

-Confirmation of IBS-D severity in terms of bowel movement frequency and abdominal pain intensity along the 2-week run-in period.

Exclusion criteria:

• Organic abnormalities of the gastrointestinal tract, including history of colonic or major abdominal surgery.
• History of gluten enteropathy.
• Lactose intolerance as assessed by response to diet.
• History of positive tests for ova or parasites, or occult blood in the stool.
• Previous diagnosis of diabetes mellitus (either type 1 or 2).
• Unstable medical condition.
• Major psychiatric, neurological, or cardiovascular disorders, or uncontrolled metabolic disease.
• Relevant changes in dietary habits, lifestyle, or exercise regimen in the previous 2 months.
• Use of concurrent medication with drugs known to interfere with gastro-intestinal motility or sensitivity.
• Pregnancy or breastfeeding.