A Study to Evaluate the Efficacy and Safety of 2 Dose Regimens of Intravenous TAK-954 for the Prophylaxis and Treatment of Postoperative Gastrointestinal Dysfunction in Participants Undergoing Large- and Small-Bowel Resection

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 gastrointestinal (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 375 patients. Participants will be randomly assigned in
1:1:1:1:1 ratio to one of the five treatment arms—which will remain undisclosed to the
patient and study doctor during the study (unless there is an urgent medical need).

All participants will be given IV 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 North America and Europe. 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 after return of GI function post-surgery (whichever occurs
first).

Inclusion Criteria:

1. Participant is scheduled to undergo a laparoscopic-assisted or open partial small- or
large- bowel resection.

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 (eg, gastroparesis, scleroderma, chronic intestinal pseudo-obstruction),
uncontrolled diabetes (glycosylated hemoglobin [HbA1c] >10%), has an active gastric
pacemaker, or requires parenteral nutrition.

2. Had previous major abdominal surgery (eg, gastrectomy, gastric bypass, gastric sleeve,
lap banding, Whipple, pancreatic resection, total/subtotal colectomy, hemicolectomy,
extensive bowel resection).

3. Scheduled to undergo any of the following surgeries: low anterior resection, total or
subtotal colectomy, colostomy, ileostomy or reversal of stoma.

4. 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).

5. Has received alvimopan, erythromycin, prucalopride, metoclopramide, domperidone, or
azithromycin in the 24 hours prior to surgery or during the study period.

6. Had a history of radiation therapy to the abdomen or pelvis.