A Safety and Efficacy Study of Daikenchuto (TU-100) to Relieve Abdominal Bloating in Female Subjects With Irritable Bowel Syndrome

Study Overview
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Brief Summary
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The aim of this study is to assess the effect of orally administered TU-100 (5 g three times daily [TID]) as compared to placebo on abdominal bloating rating in female IBS patients.

Official Title
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A Phase 2, Single-center, Randomized, Double-Blinded, Placebo-Controlled Study on the Efficacy of Daikenchuto (TU 100) to Relieve Abdominal Bloating in Female Subjects With Irritable Bowel Syndrome

Conditions
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Irritable Bowel Syndrome in Females

Intervention / Treatment
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* Drug: TU-100
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet Rome III criteria for IBS (any subtype) Female aged 18 to 65 years, inclusive If of childbearing potential, prepared to use suitable forms of contraception throughout the study and for 30 days after the last dose i.e., hormonal contraceptives (such as oral contraceptives, Depo-Provera, NuvaRing, Essure), condoms used with a spermicide, an intrauterine device, or abstinence. Females are not considered to be of childbearing potential if they are naturally postmenopausal (no menses for at least 1 year and, if < 55 years of age, have a documented follicle-stimulating hormone [FSH] level of ≥ 35 mIU/mL) or have documentation of surgical sterility Have a BMI between 18 and 30 kg/m2, inclusive Have a negative pregnancy urine screening at Visit 1, if of childbearing potential Able to provide written consent Able to take oral administration of the testing medications Have a self-reported average abdominal bloating rating (>3 daily ratings over the preceding 7 days) equal or greater than 4 on a numerical scale of 0 to 20. Exclusion Criteria: Have a structural or metabolic disease or condition that affects the GI system, excluding asymptomatic gallstones or uncomplicated gastroesophageal reflux disease, or any medical condition that may be a cause of constipation or diarrhea (e.g., hypothyroid status, poorly controlled diabetes, diabetic neuropathy or autonomic neuropathy) Be taking any medication that, in the opinion of the Principle Investigator (PI), has potential to alter GI transit. A full list of prohibited medications is provided in the protocol. Have history or presence of any chronic lung disease Have presence of hepatic dysfunction, jaundice, or abnormal serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values exceeding 2.5 x upper limit of normal Currently pregnant or lactating Have a positive urine drug test at screening (subjects who initially test positive will be allowed one retest) Be a known substance abuser or be considered to be an alcoholic not in remission Have participated in another clinical study in the past 30 days Use of supplemental ginger, ginseng, or Zanthoxylum fruit for 2 weeks prior to randomization and throughout the course of the study. Have a history of allergic reaction to ginseng, ginger or Zanthoxylum fruit Be clinically lactose-intolerant Have any other condition that, in the opinion of the PI, causes the subject to be unsuitable to participate Have taken antibiotics in the last 3 months Have had gastroenteritis (stomach flu) in the last 3 months Have taken probiotics in the last 3 months (over-the-counter [OTC] products or supplements only; food products such as yogurts are permitted).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TU-100<br>15g TU-100 (oral, daily) for 4 consecutive weeks (administered as 5g three times daily) | Drug: TU-100<br>* 15g daily, orally as 5g three times daily for 4 consecutive weeks<br>* Other names: Daikenchuto;|
| Placebo Comparator: Matching placebo<br>Matching placebo given 5g three times daily orally for 4 consecutive weeks | Drug: Placebo<br>* Matching placebo given 5g three times daily orally for 4 consecutive weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abdominal bloating rating | Change in abdominal bloating rating, through comparison of the change in average ratings from the 7 days prior to baseline (Visit 2) to the last 7 days of the 4 week treatment period (Visit 4), between TU-100 15 g and placebo. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC for abdominal bloating ratings using lactulose challenge | Change in area under the curve (AUC) for abdominal bloating ratings obtained during the lactulose challenge at Visit 2 (baseline) and at Visit 4 (4 weeks). The data are collected at -0.5, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8 hours after taking test meal (lactulose). | Baseline and 4 weeks | 
| Abdominal bloating ratings | Change in the average of abdominal bloating ratings from the 7 days prior to baseline to the 7 days prior to Visit 3 (2 weeks) and to Visit 5 (8 weeks) | 4 weeks | 
| Overall IBS Severity | Change in Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) total score from baseline to Visits 3, 4, and 5 | 4 weeks | 
| GI symptom ratings | Change in the average of GI symptom ratings from the 7 days prior to baseline to the 7 days prior to Visit 3 and to Visit 5 | 4 week | 
| Quality of Life effect | Change in IBS-QOL score from baseline to Visits 3, 4, and 5 | 4 weeks | 
| Mood symptom ratings | Change in the average of mood symptom ratings from the 7 days prior to baseline to the 7 days prior to Visit 3 and to Visit 5 | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Irritable Bowel Syndrome, Rome III criteria, abdominal bloating, natural, herbal, Kampo, Adult ages 18 to 65, Female subjects