Clinical trial NCT03827655: A Study of TAK-954 to Treat Gastrointestinal Dysfunction in Adults After Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postoperative Gastrointestinal Dysfunction
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2019-02-01
Enrollment: 209
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Time From End of the Surgery to Resolution of Upper and Lower Gastrointestinal (GI) Function Postsurgery as Assessed by the Investigator
timeFrame: Day 1 (surgery) up to Day 10 postsurgery
Secondary outcomes:
measure: Time From the End of the Surgery (Time the Incision is Closed) Until Ready for Discharge as Assessed by the Investigator
timeFrame: Day 1 (surgery) up to Day 24
measure: Time From the End of Surgery Until the Discharge Order is Written
timeFrame: Day 1 (surgery) up to Day 24
measure: Time From the End of Surgery to Discharge From Hospital
timeFrame: Day 1 (surgery) up to Day 24
measure: Time From End of Surgery to Tolerance of Solid Food as Assessed by the Investigator
timeFrame: Day 1 (surgery) up to Day 10 postsurgery
measure: Time From End of Surgery to First Spontaneous Bowel Movement as Assessed by the Investigator
timeFrame: Day 1 (surgery) up to Day 10 postsurgery
measure: Percentage of Participants With Postoperative Gastrointestinal Dysfunction (POGD) >= 5 Days as Assessed by the Investigator
timeFrame: Day 1 (surgery) up to Day 10
measure: Percentage of Participants Requiring Insertion of Nasogastric (NG) Tube Postsurgery
timeFrame: 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)
measure: Time From End of Surgery to First Flatus
timeFrame: Day 1 (surgery) up to first flatus (up to Day 10 postsurgery)
measure: Observed Plasma Concentration of TAK-954 at the End of Infusion on Day 1
timeFrame: Day 1 (surgery): postinfusion
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Medical Center
state: Alabama
city: Los Angeles
country: United States
facility: Keck School of Medicine
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Riverside
country: United States
facility: Parkview Community Hospital Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Miami
country: United States
facility: University of Miami Leonard M. Miller School of Medicine
state: Florida
city: Orlando
country: United States
facility: Center for Colon & Rectal Surgery - Altamonte Springs
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Cleveland
country: United States
facility: Fairview Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: HD Research Corp.
state: Texas
city: Houston
country: United States
facility: North Star Medical
state: Texas
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
state: Baden-wuerttemberg
city: Mannheim
country: Germany
facility: Universitatsklinikum Mannheim
state: Baden-wuerttemberg
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
state: Bavaria
city: Munchen
country: Germany
facility: Klinikum Rechts der Isar der Technischen Universitat Munchen
state: Bayern
city: Bochum
country: Germany
facility: Sankt Josef-Hospital
state: Nordrhein-westfalen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: