A Study of TAK-954 to Treat Gastrointestinal Dysfunction in Adults After Surgery

Takeda

Status and phase: Completed; Phase 2

Conditions: Postoperative Gastrointestinal Dysfunction

Treatments: Drug: TAK-954; Drug: TAK-954 Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03827655

2018-003318-42 (EudraCT Number)

TAK-954-2004

U1111-1222-4784 (Registry Identifier)

Details and patient eligibility

About

The main aim of this study is to check for side effects from TAK-954 and whether it speeds up the recovery of gastrointestinal function after small-bowel or large-bowel resection surgery.

Participants will be treated with TAK-954 before surgery and up to 10 days after surgery.

Full description

The drug being tested in this study is called TAK-954. In this study TAK-954 is being administered presurgery to evaluate if it can enhance the recovery of GI function postsurgery in participants undergoing open or laparoscopic-assisted partial small- or large-bowel resection. In addition, some participants will also receive TAK-954 postoperatively to evaluate if there is an additional benefit when this drug is administered both pre and post-surgery.

The study will enroll approximately 180 participants. Participants will be equally randomized into one of the three remaining parallel treatment arms- which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).

All participants will be given intravenous infusion preoperation and daily postoperation until return of upper and lower GI function or for up to 10 days.

This multi-center trial will be conducted in the United States and Germany. The overall time to participate in this study is up to 100 days. Participants will be treated with the study drug for up to 10 days after surgery or until return of GI function post-surgery (whichever occurs first).

Enrollment: 209 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Participant is scheduled to undergo a laparoscopic-assisted or open partial small- or large-bowel resection.
2. Participant's American Society of Anesthesiologists (ASA) physical status classification is ASA 1 to 3.

Exclusion criteria

1. Has significant mechanical bowel obstruction that is not expected to resolve after the surgery, short bowel syndrome, pre-existing clinically significant GI motility disorder (example, gastroparesis, scleroderma, chronic intestinal pseudo-obstruction), uncontrolled diabetes (glycosylated hemoglobin [HbA1c] greater than [>] 10 percent [%]), has an active gastric pacemaker, or requires parenteral nutrition.
2. Had previous major abdominal surgery (example, gastrectomy, gastric bypass, gastric sleeve, lap banding, Whipple, pancreatic resection, total/subtotal colectomy, hemicolectomy, extensive bowel resection).
3. Had a history of radiation therapy to the abdomen or pelvis.
4. Scheduled to undergo any of the following surgeries: low anterior resection, total or subtotal colectomy, colostomy, ileostomy or reversal of stoma, or has a diagnosis that requires rectal resection (eg, tumors in the anorectum) and will likely require lower anterior resection surgery. Participants with planned surgery for which there is no anticipated significant rectal resection and is, therefore, likely to preserve anorectal function and continence postsurgery, will likely be eligible for inclusion in the study if they meet all the study inclusion/exclusion criteria (eg, participants with lesions not involving the rectum [sigmoid colon and above]).
5. Has pre-existing hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points).
6. Has received alvimopan, erythromycin, prucalopride, metoclopramide, domperidone, cisapride, mosapride, renzapride, or azithromycin in the 24 hours prior to starting study drug.
7. Participant has known COVID-19 infection, or suspected COVID-19 infection.
8. Scheduled for abdominal surgery that is classified as emergency.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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209 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.

Treatment:

Drug: TAK-954 Placebo

TAK-954 0.1 mg/100 mL

Experimental group

Description:

TAK-954 0.1 milligrams per 100 milliliters (mg/100 mL), 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.

Treatment:

Drug: TAK-954

TAK-954 0.5 mg/100 mL

Experimental group

Description:

TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.

Treatment:

Drug: TAK-954

TAK-954 0.1 mg/100 mL + Placebo

Experimental group

Description:

TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.

Treatment:

Drug: TAK-954 Placebo

Drug: TAK-954

TAK-954 0.5 mg/100 mL + Placebo

Experimental group

Description:

TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.

Treatment:

Drug: TAK-954 Placebo

Drug: TAK-954