Effect of TU-100 in Patients With Functional Constipation

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the improvement in the severity of constipation (from Baseline to Day 28), determined by the constipation severity instrument (CSI) score [1], compared to placebo, following a total daily oral dose of 15 g TU-100 administered for 28 consecutive days in adult subjects with functional constipation.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled Exploratory Study of Daikenchuto (TU-100) in Patients With Functional Constipation

Conditions
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Functional Constipation

Intervention / Treatment
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* Drug: DAIKENCHUTO (TU-100)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have severity of constipation in CSI score of 25 to 74 points. Have the ability to orally ingest study medication, TU-100, and the SmartPill capsule. Be male or female aged between 18 and 80 years old, inclusive. Provide written informed consent before participation in the study after full explanations of the study purpose and procedures. If a female is of childbearing potential and sexually active: She must agree to practice a highly effective method of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, during their participation in the trial and for 4 weeks after receiving the last dose of study drug She must have a negative serum pregnancy test before randomization. If a male is sexually active with a female of childbearing potential: He must agree to use a double barrier of birth control during the study and for 4 weeks after receiving the last dose of study drug. He must not donate sperm during the study and for 4 weeks after receiving the last dose of study drug. Exclusion Criteria: Presence of strictures, fistulas, or physiological or mechanical bowel obstruction. Presence of implanted or portable electro-mechanical medical devices. History of gastric bezoar or swallowing disorders. History of gastrointestinal surgery within 3 months of screening. History of bowel resection. Current pregnancy or lactation. History of clinically significant alcohol or drug abuse within a year of screening. Have any other condition that might adversely affect capacity to participate in this study, including liver disorders (with serum alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] levels exceeding 2.5 times the upper limit of normal [ULN]), kidney disorders, heart failure, blood disorders, or metabolic disorders. Be diagnosed with cancer, ulcerative colitis, Crohn's disease, diverticulitis, scleroderma, Hirschsprung's disease, Chagas' disease, multiple sclerosis, Parkinson's disease, stroke, paraplegia, quadriplegia, insulin-dependent diabetes mellitus, untreated hypothyroidism, or any other systemic or psychiatric disorder which may, in the opinion of the investigator, interfere with the evaluation of TU-100. Be taking any medication as follows: anticholinergic agents/medications with anticholinergic effect (list of prohibited drugs attached in Appendix G; antidepressants are permissible if the patient's symptoms are stable, and the doses are NOT changed during the course of the study), warfarin, prokinetics (i.e., Domperidone, Metoclopramide), narcotic analgesics, or any agent that might interfere with the evaluation of TU-100 in the opinion of the investigator. Have a history of allergic reaction or hypersensitivity to ginseng, ginger, and Sichuan pepper. Have severe dysphagia to food or pills. Have participated in any other clinical study within 30 days before enrolling in this study. Be unsuitable for participation in this trial for any reason, according to the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo TID | Drug: Placebo<br>* Subjects will be randomized to 15 g/day of placebo. Dosage is granule. Subjects will ingest two 2.5 g doses of placebo three times daily for 34 consecutive days.<br>|
| Experimental: DAIKENCHUTO (TU-100) 15 g/day<br>TU-100 5g TID | Drug: DAIKENCHUTO (TU-100)<br>* Subjects will be randomized to 15 g/day of TU-100. Dosage is granule. Subjects will ingest two 2.5 g doses of TU-100 three times daily for 34 consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Day 28 in CSI total score |  | Up to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in GI transit time measured by SmartPill capsule. |  | Up to 10 weeks | 
| Change from baseline to Day 28 in CRQOL total score. |  | Up to 10 weeks | 
| Changes from baseline in stool frequency, stool consistency, severity of straining, and completeness of evacuation determined from entries in the bowel pattern diary. |  | Up to 10 weeks | 
| Change from baseline to Day 28 in CSI subscale scores. |  | Up to 10 weeks | 
| Change from baseline to Day 28 in CRQOL subscale scores. |  | Up to 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Emptying