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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Enhanced Recovery After Surgery
• Intervention / Treatment: Drug: TU-100; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 402
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rebekah McLaughlin; Phone Number: 919-341-3318; Email: rebecca.mclaughlin@syneoshealth.com
• Study Contact Backup: Name: Dana Kappel; Phone Number: 919-745-2818; Email: dana.kappel@syneoshealth.com

Study Locations

• United States
  • Alabama
    • Florence, Alabama, United States, 35630
      • Recruiting
      • Florence Site
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Gilbert Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • Little Rock Site
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • Duarte Site
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Los Angeles Site #1
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Los Angeles Site #2
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Palo Alto Site
    • Sacramento, California, United States, 95817
      • Recruiting
      • Sacramento Site
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Recruiting
      • Danbury Site
  • Florida
    • Clearwater, Florida, United States, 33756
      • Recruiting
      • Clearwater Site
    • Miami, Florida, United States, 33155
      • Withdrawn
      • Miami Site
    • Orlando, Florida, United States, 32803
      • Recruiting
      • Orlando Site
    • Tampa, Florida, United States, 33606
      • Recruiting
      • Tampa Site
    • Weston, Florida, United States, 33331
      • Recruiting
      • Weston Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Chicago Site #2
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • Chicago Site #1
    • Urbana, Illinois, United States, 61801
      • Recruiting
      • Urbana Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • Lexington Site
    • Louisville, Kentucky, United States, 40202
      • Withdrawn
      • Louisville Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Recruiting
      • Metairie Site
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Withdrawn
      • Baltimore Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Site #1
    • Boston, Massachusetts, United States, 02114
      • Withdrawn
      • Boston Site #2
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Detroit Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • St. Louis Site
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Terminated
      • Newark Site
  • New York
    • Mineola, New York, United States, 11501
      • Recruiting
      • Mineola Site
    • New York, New York, United States, 10065
      • Recruiting
      • New York Site
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook Site
  • Ohio
    • Cleveland, Ohio, United States, 44111
      • Recruiting
      • Cleveland Site #2
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Site #1
    • Dayton, Ohio, United States, 45409
      • Withdrawn
      • Dayton Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Recruiting
      • Philadelphia Site #2
    • Philadelphia, Pennsylvania, United States, 19141
      • Withdrawn
      • Philadelphia Site #1
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Pittsburgh Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Charleston Site
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Recruiting
      • Memphis Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Terminated
      • Dallas Site
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Fort Worth Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • Salt Lake City Site
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Recruiting
      • Roanoke Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Milwaukee Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female ≥ 18 years of age
2. 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
3. American Society of Anesthesiologists Physical Status Score of 1 to 3
4. Scheduled for an elective BR via open or laparoscopic approach
5. Ability to understand the study procedures, have agreed to participate in the study program, and have voluntarily provided informed consent

Exclusion Criteria:

1. Scheduled for a BR that is not listed in this protocol
2. Requires any additional resections beyond the intestine (eg, hepatectomy, distal pancreatectomy, pancreaticoduodenectomy, gastric resection, uterine resection), or concomitant surgeries (with the exception of biopsies)
3. Requires the formation of a stoma (ileostomy or colostomy)
4. 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
5. Have a functional colostomy or ileostomy
6. Diagnosed with advanced or metastatic colon cancer (Stage IV by tumor, node, and metastasis classification)
7. Positive coronavirus disease 2019 (COVID-19) test
8. 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
9. Chronic pain syndrome unrelated to the planned surgery requiring consistent management with analgesics and/or other non-pharmacologic modalities
10. Myocardial infarction within 3 months
11. Corrected QT interval > 500 msec
12. Diabetic gastroparesis
13. Compromised immune system, either from treatment with corticosteroids or other immunosuppressive agent within 2 weeks of surgery or from immunosuppressive disease (HIV)
14. 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)
15. 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
16. Illicit drug use or alcohol abuse based on medical history, or currently engaged in illicit drug use or alcohol abuse
17. Uses of supplemental ginger, ginseng, or Zanthoxylum fruit within 72 hours before randomization
18. Has a history of allergic reactions to ginseng, ginger, Zanthoxylum fruit, or lactose
19. Has clinical symptoms of lactose intolerance after ingesting milk or milk-containing products (abdominal pain, flatulence, diarrhea)
20. Unwilling or unable to comply with procedures described in this protocol or is otherwise unacceptable for enrollment in the opinion of the investigator
21. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TU-100 15 g/day; 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; Treatment with investigational product; Other Names: Daikenchuto
Experimental: TU-100 7.5 g/day; 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; Treatment with investigational product; Other Names: Daikenchuto
Placebo Comparator: Placebo; Subjects will receive placebo TID until hospital discharge or ≤ 10 days (whichever is earlier).	Drug: Placebo; Treatment with placebo product

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of TU-100 on early postoperative surgical outcomes related to mechanism of action	Subject-reported (electronic diary) for number of episodes of vomiting and/or retching per day and bothersome nausea and abdominal bloating by day, postoperative antiemetic rescue, and postoperative complications	From the day after surgery to discharge follow-up visit (30 days (+ 7 days) after hospital discharge)

Collaborators and Investigators

• Sponsor: Tsumura USA

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2021
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: January 29, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (Actual): February 8, 2021

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: TU100P2T4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No