Gelsectan® in the Treatment of Patients With Diarrhoea-predominant Irritable Bowel Syndrome

Inclusion criteria:

1. Male or female, age ≥18 years and ≤ 65 years.

2. Positive diagnosis of IBS, according to Rome IV diagnostic criteria, namelyrecurrent abdominal pain, on average, at least 1 day/week in the last 3 monthsassociated with two or more of the following criteria:

• related to defecation

• associated with a change in frequency stool

• associated with a change in form (appearance) of stool The above criteria mustbe fulfilled for the last 3 months with symptom onset at least 6 months beforediagnosis.

3. Positive diagnosis of IBS-D subtype based on Rome IV diagnostic criteria, i.e., morethan 25% of bowel movements with a consistency of type 6 or type 7 (loose or waterystools) on the BSFS, and less than 25% of bowel movements with BSFS types 1 or 2 (hard or lumpy stools), on days with at least one abnormal bowel movement.

4. Negative results to any relevant additional tests or exams whenever deemedappropriate by the Investigator to exclude other disorders or causes of IBSsymptoms.

5. At least one type 6 or type 7 bowel movement based on the BSFS on at least 4 dayswithin the last week prior to randomization.

6. Weekly average score of 24-hours worst abdominal pain score ≥ 3 on NRS-11 in thelast week prior to randomization.

7. Electronic diary (e-diary) completed on at least 11 of 14 days (≥ 75%) during thescreening period (i.e., 2 weeks prior to randomization).

8. Willingness and capability to fulfil all tasks foreseen by the ClinicalInvestigation Plan (CIP).

9. Signed written informed consent.

10. Females of childbearing potential must have a negative urine pregnancy test (dipstick) at randomization and currently use or agree to use consistently andcorrectly (i.e., perfect use) a highly effective or acceptable effectivecontraceptive method for the individual subject and her partner(s) throughout thestudy treatment period and for at least one full contraceptive cycle (whenapplicable).

Exclusion criteria:

1. Presence of any relevant organic, systemic or metabolic disease (particularlysignificant history of cardiovascular, renal, neurological, endocrine, metabolic orhepatic disease) that would preclude participation in this study in the opinion ofthe Investigator, or abnormal laboratory values that will be deemed clinicallysignificant on the basis of predefined values.

2. Known perforation and/or gastrointestinal obstruction.

3. Ascertained organic gastrointestinal diseases, including celiac disease, bile acidmalabsorption or inflammatory bowel diseases (Crohn's disease, ulcerative colitis,diverticular disease, infectious colitis, ischemic colitis, microscopic colitis).

4. Presence of other intestinal motility disorders, such as biliary dyskinesia,gastroparesis, intestinal pseudo-obstruction, and narcotic bowel syndrome.

5. Previous major abdominal surgery (uncomplicated appendectomy, cholecystectomy,polypectomy, inguinal hernia surgery, or caesarean section are allowed unless withinsix months prior to screening).

6. Active malignancy of any type (except for non-invasive basal or squamous cellcarcinoma of the skin), or history of a malignancy other than non-invasive basal orsquamous cell carcinoma of the skin. Patients with a history of malignancies thathave been surgically removed with no evidence of recurrence for at least five yearsand no treatment prior to screening are allowed to participate in the study.

7. History of allergy or hypersensitivity to any of the investigational productingredients or excipients.

8. Current use of Gelsectan®.

9. Use of loperamide or antispasmodics (i.e., direct smooth muscle relaxants,anticholinergic agents and calcium channel blockers) in the 14 days prior torandomization.

10. Concomitant use (starting from screening) of weak and potent opioids, 5-HT3antagonists, such as alosetron and ondansetron, bile acid sequestrants, eluxadolineor any other drug/supplement known to significantly interfere with abdominal pain,stool frequency and consistency and/or intestinal permeability (except for thoseallowed as rescue therapy starting from randomization), including but not limited tocorticosteroids, aminosalicylates, immunosuppressants and biologicals.

11. Prior and concomitant use of probiotics/prebiotics/synbiotics or rifaximin startingfrom 28 days prior to randomization. Other oral antibiotics and topical antibioticsare allowed.

12. Any major psychiatric unstable disorder, including eating disorders, and use ofantidepressant or anxiolytic agents, unless used at a stable dose for at least 6weeks prior to randomization.

13. History or current evidence of laxative abuse within 5 years prior to screening.

14. Recent history (within 12 months prior to screening) or suspicion of alcohol abuseor drug addiction.

15. Treatment with any investigational drug or medical device within 30 days prior torandomization, or current participation in other clinical trials or investigations.

16. Pregnancy or breastfeeding or intention to look for pregnancy throughout the wholestudy duration.