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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03827655
• Collaborator: Takeda Development Center Americas, Inc. (Industry)
• Enrollment: 210
• Locations: 25
• Arms: 3
• Actual Duration (Months): 38.7
• Patients Per Site: 8.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Gastrointestinal Dysfunction	Drug: TAK-954 Placebo; Drug: TAK-954	Phase 2

Detailed 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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose Ranging 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 Patients Undergoing Large- and Small-Bowel Resection
• Actual Study Start Date: Mar 7, 2019
• Actual Primary Completion Date: May 27, 2022
• Actual Study Completion Date: May 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo TAK-954 placebo-matching, 60-minute infusion, intravenously, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	Drug: TAK-954 Placebo; TAK-954 placebo-matching intravenous infusion.
Experimental: TAK-954 0.5 mg/100 mL TAK-954 0.5 mg/100 mL, 60-minute infusion, intravenously, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	Drug: TAK-954; TAK-954 intravenous infusion.
Experimental: TAK-954 0.5 mg/100 mL + Placebo TAK-954 0.5 mg/100 mL, 60-minute infusion, intravenously, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	Drug: TAK-954 Placebo; TAK-954 placebo-matching intravenous infusion.; Drug: TAK-954; TAK-954 intravenous infusion.

Outcome Measures

Primary Outcome Measures

1. Time From End of the Surgery to Resolution of Upper and Lower GI Function Postsurgery as Assessed by the Investigator [Day 1 (surgery) up to Day 10 postsurgery]

   The time from end of surgery to tolerance of solid food, without first occurrence of vomiting or clinically significant nausea for 1 calendar day after a solid meal (upper GI function) and first spontaneous bowel movement (lower GI function), whichever occurs later up to 10 days postsurgery will be observed.

Secondary Outcome Measures

1. Time From the End of the Surgery (Time the Incision is Closed) Until Ready for Discharge as Assessed by the Investigator [Day 1 (surgery) up to Day 10]

   The time from the end of surgery (time the incision is closed) until ready for discharge is defined as time from end of surgery until the participant presents effective intestinal transit (spontaneous bowel movement), tolerates solids without vomiting or clinically significant nausea for 1 calendar day after a solid meal, has satisfactory pain control with oral analgesics, and is medically stable/free of complications.

2. Time From the End of Surgery Until the Discharge Order is Written [Day 1 (surgery) until day discharged (approximately 10 days postsurgery)]

3. Time From the End of Surgery to Discharge From Hospital [Day 1 (surgery) until day discharged (approximately 10 days postsurgery)]

4. Time From End of Surgery to Tolerance of Solid Food as Assessed by the Investigator [Day 1 (surgery) up to Day 10 postsurgery]

   The time from end of surgery to tolerance of solid food is defined as intake of solids without vomiting or clinically significant nausea for 1 calendar day after a solid meal.

5. Time From End of Surgery to First Spontaneous Bowel Movement as Assessed by the Investigator [Day 1 (surgery) up to Day 10 postsurgery]

   The time from end of surgery to first spontaneous bowel movement is defined as a stool not induced by the use of enemas or laxatives.

6. Percentage of Participants with Postoperative Gastrointestinal Dysfunction (POGD) >= 5 Days as Assessed by the Investigator [Day 1 (surgery) up to Day 10]

   Participants unable to tolerate solid foods, take anything by mouth, or requiring insertion or reinsertion of nasogastric (NG) tube at or after 5 days post-surgery.

7. Percentage of Participants Requiring Insertion of NG Tube Postsurgery [Day 1 (surgery) up to Day 24 postsurgery (10 days of treatment period postsurgery plus 14-day observation period post last dose for recurrence of symptoms)]

   Participants who would require insertion of NG tube postsurgery for drainage and symptom relief in case of persistent nausea and vomiting postsurgery will be observed.

8. Time From End of Surgery to First Flatus [Day 1 (surgery) up to first flatus (up to Day 10 postsurgery)]

9. Observed Plasma Concentration of TAK-954 at the End of Infusion on Day 1 [Day 1 (surgery): preinfusion and postinfusion]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama Medical Center	Mobile	Alabama	United States	30617
2	Keck School of Medicine	Los Angeles	California	United States	90007
3	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
4	University of California Irvine Medical Center	Orange	California	United States	92868
5	Parkview Community Hospital Medical Center	Riverside	California	United States	92504
6	University of Colorado	Aurora	Colorado	United States	80045
7	University of Miami Leonard M. Miller School of Medicine	Miami	Florida	United States	33136
8	Center for Colon & Rectal Surgery - Altamonte Springs	Orlando	Florida	United States	32804
9	Cleveland Clinic Florida	Weston	Florida	United States	33331
10	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
11	University of Kentucky	Lexington	Kentucky	United States	40536
12	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
13	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01605
14	Stony Brook University Hospital	Stony Brook	New York	United States	11794
15	Fairview Hospital	Cleveland	Ohio	United States	44111
16	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
17	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
18	HD Research Corp.	Houston	Texas	United States	77024
19	North Star Medical	Houston	Texas	United States	77089
20	Universitatsklinikum Freiburg	Freiburg	Baden-wuerttemberg	Germany	79106
21	Universitatsklinikum Mannheim	Mannheim	Baden-wuerttemberg	Germany	68167
22	Universitaetsklinikum Regensburg	Regensburg	Bavaria	Germany	93053
23	Klinikum Rechts der Isar der Technischen Universitat Munchen	Munchen	Bayern	Germany	81675
24	Sankt Josef-Hospital	Bochum	Nordrhein-westfalen	Germany	44791
25	Universitaetsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246

Sponsors and Collaborators

• Takeda
• Takeda Development Center Americas, Inc.

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain more information on the study, click here/on this link.

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03827655
• Other Study ID Numbers: TAK-954-2004; 2018-003318-42; U1111-1222-4784
• First Posted: Feb 1, 2019
• Last Update Posted: Jun 7, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug Therapy

Study Results

No Results Posted as of Jun 7, 2022