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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Irritable Bowel Syndrome With Diarrhea

Intervention / Treatment
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* Drug: DT01 tablets
* Drug: Placebo tablets
* Drug: DT01-Placebo tablets


Participation Criteria
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Eligibility Criteria
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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: 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). At least one bowel movement on each day. A weekly average of at least 3 bowel movements per day. 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. Less than 2 bowel movements with a consistency of Type 1 or Type 2 according to the BSS per week. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo tablets<br>Posology: oral administration of 3 placebo tablets three times per day for 8 weeks. | Drug: Placebo tablets<br>* Each subject was given orally 3 DT01 tablets/day for 8 weeks<br>|
| Experimental: DT01 tablets<br>Posology: oral administration of 3 DT01 tablets three times per day for 8 weeks. | Drug: DT01 tablets<br>* Each subject was given orally 3 DT01 tablets/day for 8 weeks<br>|
| Experimental: DT01-Placebo tablets<br>Posology: oral administration of 2 DT01 tablets and 1 placebo tablet, three times per day for 8 weeks. | Drug: DT01-Placebo tablets<br>* Each subject was given orally 2 DT01 tablets and 1 Placebo tablet, three times per day for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abdominal pain response | Decrease in the weekly average of worst abdominal pain score in the past 24 hours of at least 30% compared with baseline | 8 weeks | 
| Stool consistency response | Decrease of at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7 according to the Bristol Stool Scale (BSS) compared with baseline. | 8 weeks | 
| Weekly response for abdominal pain intensity and stool consistency over 8 weeks of treatment in at least 50% of the weeks of treatment (4 out of 8 weeks) | A participant must meet both of the Abdominal pain response and Stool consistency response in the same week to be a weekly responder. | 8 weeks |