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

Enhanced Recovery After Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04742907
• Other study ID #: TU100P2T4
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 29, 2021
• Est. completion date: May 2024

Study information

• Verified date: May 2024
• Source: Tsumura USA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 402
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Enhanced Recovery After Surgery

Intervention

Drug:
• TU-100
Treatment with investigational product
• Placebo
Treatment with placebo product

Locations

Country	Name	City	State
United States	Boston Site #1	Boston	Massachusetts
United States	Charleston Site	Charleston	South Carolina
United States	Chicago Site #1	Chicago	Illinois
United States	Chicago Site #2	Chicago	Illinois
United States	Clearwater Site	Clearwater	Florida
United States	Cleveland Site #1	Cleveland	Ohio
United States	Cleveland Site #2	Cleveland	Ohio
United States	Dallas Site	Dallas	Texas
United States	Danbury Site	Danbury	Connecticut
United States	Detroit Site	Detroit	Michigan
United States	Duarte Site	Duarte	California
United States	Florence Site	Florence	Alabama
United States	Fort Worth Site	Fort Worth	Texas
United States	Gilbert Site	Gilbert	Arizona
United States	Lexington Site	Lexington	Kentucky
United States	Little Rock Site	Little Rock	Arkansas
United States	Los Angeles Site #1	Los Angeles	California
United States	Los Angeles Site #2	Los Angeles	California
United States	Memphis Site	Memphis	Tennessee
United States	Metairie Site	Metairie	Louisiana
United States	Milwaukee Site	Milwaukee	Wisconsin
United States	Mineola Site	Mineola	New York
United States	New York Site	New York	New York
United States	Newark Site	Newark	New Jersey
United States	Orlando Site	Orlando	Florida
United States	Palo Alto Site	Palo Alto	California
United States	Philadelphia Site #2	Philadelphia	Pennsylvania
United States	Pittsburgh Site	Pittsburgh	Pennsylvania
United States	Roanoke Site	Roanoke	Virginia
United States	Sacramento Site	Sacramento	California
United States	St. Louis Site	Saint Louis	Missouri
United States	Salt Lake City Site	Salt Lake City	Utah
United States	Stony Brook Site	Stony Brook	New York
United States	Tampa Site	Tampa	Florida
United States	Urbana Site	Urbana	Illinois
United States	Weston Site	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Tsumura USA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)