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

Postoperative Gastrointestinal Dysfunction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03827655
• Other study ID #: TAK-954-2004
• Secondary ID: 2018-003318-42U1
• Status: Completed
• Phase: Phase 2
• Start date: March 7, 2019
• Est. completion date: May 27, 2022

Study information

• Verified date: May 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 209
• Est. completion date: May 27, 2022
• Est. primary completion date: May 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Postoperative Gastrointestinal Dysfunction

Intervention

Drug:
• TAK-954 Placebo
TAK-954 placebo-matching intravenous infusion.
• TAK-954
TAK-954 intravenous infusion.

Locations

Country	Name	City	State
Germany	Sankt Josef-Hospital	Bochum	Nordrhein-westfalen
Germany	Universitatsklinikum Freiburg	Freiburg	Baden-wuerttemberg
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitatsklinikum Mannheim	Mannheim	Baden-wuerttemberg
Germany	Klinikum Rechts der Isar der Technischen Universitat Munchen	Munchen	Bayern
Germany	Universitaetsklinikum Regensburg	Regensburg	Bavaria
United States	University of Colorado	Aurora	Colorado
United States	Fairview Hospital	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	HD Research Corp.	Houston	Texas
United States	North Star Medical	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Kentucky	Lexington	Kentucky
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Keck School of Medicine	Los Angeles	California
United States	University of Miami Leonard M. Miller School of Medicine	Miami	Florida
United States	University of South Alabama Medical Center	Mobile	Alabama
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	University of California Irvine Medical Center	Orange	California
United States	Center for Colon & Rectal Surgery - Altamonte Springs	Orlando	Florida
United States	Parkview Community Hospital Medical Center	Riverside	California
United States	Stony Brook University Hospital	Stony Brook	New York
United States	Cleveland Clinic Florida	Weston	Florida
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	Takeda Development Center Americas, Inc.

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time From End of the Surgery to Resolution of Upper and Lower Gastrointestinal (GI) Function Postsurgery as Assessed by the Investigator	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 occurred later up to 10 days postsurgery was observed. Kaplan-Meier survival analysis method was used.	Day 1 (surgery) up to Day 10 postsurgery
Secondary	Time From the End of the Surgery (Time the Incision is Closed) Until Ready for Discharge as Assessed by the Investigator	The time from the end of surgery (time the incision is closed) until ready for discharge was defined as time from end of surgery until the participant presented effective intestinal transit (spontaneous bowel movement), tolerated solids without vomiting or clinically significant nausea for 1 calendar day after a solid meal, had satisfactory pain control with oral analgesics, and was medically stable/free of complications. Kaplan-Meier survival analysis method was used.	Day 1 (surgery) up to Day 24
Secondary	Time From the End of Surgery Until the Discharge Order is Written	Kaplan-Meier survival analysis method was used.	Day 1 (surgery) up to Day 24
Secondary	Time From the End of Surgery to Discharge From Hospital	Kaplan-Meier survival analysis method was used.	Day 1 (surgery) up to Day 24
Secondary	Time From End of Surgery to Tolerance of Solid Food as Assessed by the Investigator	The time from end of surgery to tolerance of solid food was defined as intake of solids without vomiting or clinically significant nausea for 1 calendar day after a solid meal. Kaplan-Meier survival analysis method was used.	Day 1 (surgery) up to Day 10 postsurgery
Secondary	Time From End of Surgery to First Spontaneous Bowel Movement as Assessed by the Investigator	The time from end of surgery to first spontaneous bowel movement was defined as a stool not induced by the use of enemas or laxatives. Kaplan-Meier survival analysis method was used.	Day 1 (surgery) up to Day 10 postsurgery
Secondary	Percentage of Participants With Postoperative Gastrointestinal Dysfunction (POGD) >= 5 Days as Assessed by the Investigator	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. Percentages are rounded off to whole number at the nearest single decimal. Stratified Miettinen and Nurminen approach was used for analysis.	Day 1 (surgery) up to Day 10
Secondary	Percentage of Participants Requiring Insertion of Nasogastric (NG) Tube Postsurgery	Participants who required insertion of NG tube postsurgery for drainage and symptom relief in case of persistent nausea and vomiting postsurgery were observed. Percentages are rounded off to whole number at the nearest single decimal. Stratified Miettinen and Nurminen approach was used for analysis.	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)
Secondary	Time From End of Surgery to First Flatus	Kaplan-Meier survival analysis method was used.	Day 1 (surgery) up to first flatus (up to Day 10 postsurgery)
Secondary	Observed Plasma Concentration of TAK-954 at the End of Infusion on Day 1		Day 1 (surgery): postinfusion

External Links

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