Safety and Efficacy of TU-100 as an Adjunct to an Enhanced Recovery After Surgery in Subjects Undergoing Bowel Resection

Study Overview
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Brief Summary
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This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the effect of TU-100 on resolution of postoperative ileus (POI) in subjects undergoing open or laparoscopic bowel resection (BR).

Detailed Description
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Subjects will be screened up to 28 days before their planned surgery and will be randomized 1:1:1 (TU-100 15 g/day: TU-100 7.5 g/day: placebo) on postoperative Day 1 before the first dose of study medication. After randomization, subjects will receive a total daily dose of TU-100 15g, TU-100 7.5 g, or matching placebo (3 times per day (TID)) until hospital discharge or ≤ 10 days (whichever is earlier). All subjects will be treated with study medication as adjunct to an enhanced recovery (ERAS) pathway for gastrointestinal (GI) recovery.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the Safety and Efficacy of TU-100 as an Adjunct to an Enhanced Recovery After Surgery (ERAS) Protocol in Subjects Undergoing Bowel Resection

Conditions
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Enhanced Recovery After Surgery

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: Male or female ≥ 18 years of age Women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP; must be able and willing to use at least 1 highly effective method of contraception during the study and for 30 days after the last dose of study drug American Society of Anesthesiologists Physical Status Score of 1 to 3 Scheduled for an elective BR via open or laparoscopic approach Ability to understand the study procedures, have agreed to participate in the study program, and have voluntarily provided informed consent Exclusion Criteria: Scheduled for a BR that is not listed in this protocol Requires any additional resections beyond the intestine (eg, hepatectomy, distal pancreatectomy, pancreaticoduodenectomy, gastric resection, uterine resection), or concomitant surgeries (with the exception of biopsies) Requires the formation of a stoma (ileostomy or colostomy) History of surgeries, illness, or behavior (eg, depression, psychosis) that in the opinion of the investigator might confound the study results or pose additional risk in administering the study procedures Have a functional colostomy or ileostomy Diagnosed with advanced or metastatic colon cancer (Stage IV by tumor, node, and metastasis classification) Positive coronavirus disease 2019 (COVID-19) test Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including human immunodeficiency virus (HIV)), diabetes, symptomatic congestive heart failure and ejection fraction < 35%, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with protocol requirements Chronic pain syndrome unrelated to the planned surgery requiring consistent management with analgesics and/or other non-pharmacologic modalities Myocardial infarction within 3 months Corrected QT interval > 500 msec Diabetic gastroparesis Compromised immune system, either from treatment with corticosteroids or other immunosuppressive agent within 2 weeks of surgery or from immunosuppressive disease (HIV) Pregnant (identified by a positive serum pregnancy test) or lactating, or are not postmenopausal (no menses for at least 1 year) and are of childbearing potential and not using an accepted method of birth control (surgical sterilization, intrauterine contraceptive device, oral contraceptive, diaphragm, or condom in combination with contraceptive cream, jelly, or foam or abstinence) Participated in another investigational drug/biologic or medical device study within 30 days of surgery or will be enrolled in another investigational drug or medical device study, or any study in which active subject participation is required outside routine hospital data collection during the course of the study Illicit drug use or alcohol abuse based on medical history, or currently engaged in illicit drug use or alcohol abuse Uses of supplemental ginger, ginseng, or Zanthoxylum fruit within 72 hours before randomization Has a history of allergic reactions to ginseng, ginger, Zanthoxylum fruit, or lactose Has clinical symptoms of lactose intolerance after ingesting milk or milk-containing products (abdominal pain, flatulence, diarrhea) Unwilling or unable to comply with procedures described in this protocol or is otherwise unacceptable for enrollment in the opinion of the investigator Has a history of previous surgeries, illness (interstitial pneumonia), or behavior (depression, psychosis) that, in the opinion of the investigator, might confound the study results or pose additional risk in administering the study procedures

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Randomized, Double-Blind, Placebo-Controlled
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TU-100 15 g/day<br>Subjects will receive a total daily dose of TU-100 5 g TID until hospital discharge or ≤ 10 days (whichever is earlier). | Drug: TU-100<br>* Treatment with investigational product<br>* Other names: Daikenchuto;|
| Experimental: TU-100 7.5 g/day<br>Subjects will receive a total daily dose of TU-100 2.5 g TID until hospital discharge or ≤ 10 days (whichever is earlier). | Drug: TU-100<br>* Treatment with investigational product<br>* Other names: Daikenchuto;|
| Placebo Comparator: Placebo<br>Subjects will receive placebo TID until hospital discharge or ≤ 10 days (whichever is earlier). | Drug: Placebo<br>* Treatment with placebo product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to gastrointestinal recovery (GIR) | Time to achieve recovery of GI motility as measured by a composite endpoint representing upper AND lower GI recovery | From the day after surgery until hospital discharge or ≤ 10 days (whichever is earlier) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to GIR responses | Time to first toleration of clear liquids, time to transition from clear liquids to next diet stage (full liquids or solids), time to toleration of solids, time to first bowel movement, and time to absence of distension and presence of bowel sounds and flatus | From the day after surgery until hospital discharge or ≤ 10 days (whichever is earlier) | 
| GIR outcome related to length of hospitalization | Total number of calendar days from surgery to ready for discharge based solely on GI recovery | From surgery to hospital discharge based on GI recovery (up to 2 weeks) | 
| POI-related morbidity | Primary POI that is not secondary to surgical complication, such as anastomotic leak, abscess formation, or sepsis that requires readmission within 7 days of discharge, or need for postoperative nasal gastric tube insertion to manage symptoms of POI (vomiting/retching, abdominal distension) | From the day after surgery to discharge follow-up visit (30 days (+ 7 days) after hospital discharge) | 
| Safety of TU-100 | Patient incidence of adverse events (AEs) observed following administration of TU-100. | From baseline to discharge follow-up visit (30 days (+ 7 days) after hospital discharge) |