Efficacy and Safety of DT01 Tablets in Patients With Irritable Bowel Syndrome With Diarrhea

A Phase II, Double-blind, Randomized, Parallel-group, Placebo-controlled Trial to Evaluate the Efficacy and Safety of DT01 Tablets in Patients With Irritable Bowel Syndrome With Diarrhea

This is a Phase II, double-blind, randomized, 3-arm, placebo-controlled study to evaluate the efficacy and describe the safety of DT01 tablets in adults with IBS-D.

Patients who meet all entry criteria will be randomized to receive DT tablets or placebo or both for 8 weeks. The study drug will be taken three times daily. Investigators will conduct phone-based assessments on Days 7, 14, 21, 28, 35, 42, 49. Patients will return to the clinic after dosing has completed (Day 56) for a follow-up visit.

Inclusion Criteria:

• Patients aged 18 years or older.
• Has a diagnosis of IBS-D (Irritable Bowel Syndrome with Diarrhea) and meets the Rome IV Criteria
• 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 2 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 12 months.
• 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.
• For women of childbearing potential: Use of a highly effective contraceptive method with a failure rate <1% per year throughout the entire study 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 according to the Visual Analogue Scale (VAS).
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 diary recording procedure defined as at least ≥80% of the nominal daily data entry.

Exclusion Criteria:

• Diagnosis of IBS with a subtype of constipation, mixed IBS, or un-subtyped IBS.
• 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.
• Hypersensitivity to the active substances or to any of the excipients of study drug or placebo.
• History of major cardiovascular events in the previous 6 months.
• History of human immunodeficiency virus infection.
• Uncontrolled hypertension, insulin-dependent diabetes mellitus or abnormal thyroid function.
• Evidence of clinically significant hepatic disease, severe renal insufficiency or anemia.
• 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 concomitant enrollment in a clinical study.
• Any condition that would compromise the well-being of the patient.