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

Tsumura

Status and phase: Completed; Phase 2

Conditions: Enhanced Recovery After Surgery

Treatments: Drug: TU-100; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04742907

TU100P2T4

Details and patient eligibility

About

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).

Full 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.

Enrollment: 402 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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402 participants in 3 patient groups, including a placebo group

TU-100 15 g/day

Experimental group

Description:

Subjects will receive a total daily dose of TU-100 5 g TID until hospital discharge or ≤ 10 days (whichever is earlier).

Treatment:

Drug: TU-100

TU-100 7.5 g/day

Experimental group

Description:

Subjects will receive a total daily dose of TU-100 2.5 g TID until hospital discharge or ≤ 10 days (whichever is earlier).

Treatment:

Drug: TU-100

Placebo

Placebo Comparator group

Description:

Subjects will receive placebo TID until hospital discharge or ≤ 10 days (whichever is earlier).

Treatment:

Drug: Placebo