A Study of Naldemedine in Participants Undergoing Surgeries That Include a Bowel Resection or Bowel Transection

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Naldemedine in Patients Undergoing Surgeries That Include a Bowel Resection or Bowel Transection

The objective of this study is to compare the efficacy of naldemedine versus placebo and to assess its effect on the time to gastrointestinal (GI) recovery following surgeries that include bowel resection and bowel transection.

Study Overview

• Status: Terminated
• Conditions: Postoperative Gastrointestinal Dysfunction
• Intervention / Treatment: Drug: Placebo; Drug: Naldemedine

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Hospital
    • Louisville, Kentucky, United States, 40202
      • Norton Hospital
    • Louisville, Kentucky, United States, 40208
      • University of Louisville Division of Surgery
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Tyler, Texas, United States, 75702
      • CHRISTUS Trinity Clinic Research
    • Tyler, Texas, United States, 75701
      • CHRISTUS Mother Frances Hospital - Tyler
    • Tyler, Texas, United States, 75702
      • CHRISTUS Trinity Clinic Surgical Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Scheduled to undergo 1 of the following procedures via open (nonlaparoscopic) surgery under general anesthesia:

  • partial small or large bowel resection with primary anastomosis
  • radical cystectomy requiring bowel transection with primary anastomosis

• Planned to be managed postoperatively with an enhanced recovery protocol, which, at a minimum, includes all of the following elements:

  • early removal of the nasogastric tube, which is defined as removal of the nasogastric tube at the end of surgery
  • early ambulation, which is defined as ambulation on Day 1
  • early diet advancement on Day 1
• Planned to receive primary postoperative pain management with opioid analgesia administered by any route.
• American Society of Anesthesiologists (ASA) Physical Status Score of I, II, or III (a normal healthy participant, a participant with mild systemic disease, and a participant with systemic disease, respectively).

Exclusion Criteria:

• Scheduled to undergo a total colectomy or any procedure that results in a colostomy or ileostomy.
• Scheduled for endoscopic or laparoscopic surgery.
• Complete bowel obstruction.
• Complicated inflammatory bowel disease (such as ulcerative colitis or Crohn's disease).
• More than 2 major abdominal surgery (for example, gastrectomy, gastric bypass, gastric sleeve, lap banding, pancreatic resection, hepatectomy, intestinal transplant).
• More than 3 doses of an opioid (regardless of the route of administration) during the 7 days prior to surgery.
• Pregnancy or lactation.
• Presence of peritoneal catheter (for example, for dialysis or chemotherapy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Naldemedine 1.25 mg; Participants will receive 1.25 milligrams (mg) naldemedine twice daily (BID) beginning on the day of surgery (Day 1) and for up to a maximum of 10 days post-surgery.	Drug: Naldemedine; Oral tablet; Other Names: S-297995
Experimental: Naldemedine 2.5 mg; Participants will receive 2.5 mg naldemedine BID beginning on the day of surgery (Day 1) and for up to a maximum of 10 days post-surgery.	Drug: Naldemedine; Oral tablet; Other Names: S-297995
Experimental: Naldemedine 5 mg; Participants will receive 5 mg naldemedine BID beginning on the day of surgery (Day 1) and for up to a maximum of 10 days post-surgery.	Drug: Naldemedine; Oral tablet; Other Names: S-297995
Placebo Comparator: Placebo; Participants will receive matching placebo BID beginning on the day of surgery (Day 1) and for up to a maximum of 10 days post-surgery.	Drug: Placebo; Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time From the End of Surgery to Time to First Toleration of Solid Food and First Bowel Movement (GI2)	Up to 10 days After Surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Time From the End of Surgery to Time When the Discharge Order is Written	Up to 10 days After Surgery
Percentage of Participants Requiring Postoperative Reinsertion of the Nasogastric Tube	Up to 10 days After Surgery
Percentage of Participants With Nausea on Days 1 Through 3	Days 1 to 3 After Surgery
Percentage of Participants With Vomiting on Days 1 Through 3	Days 1 to 3 After Surgery
Percentage of Participants Discharged by Day 10 Who Are Readmitted for Any Reason Within 30 Days After Discharge From the Hospital	From the Discharge Date (Days 1-10) up to 30 Days After Discharge

Collaborators and Investigators

• Sponsor: Shionogi

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2020
• Primary Completion (Actual): January 4, 2021
• Study Completion (Actual): January 4, 2021

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 17, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2022
• Last Update Submitted That Met QC Criteria: December 17, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Bowel resection; Gastrointestinal recovery; peripherally acting mu-opioid receptor antagonist; Bowel transection
• Other Study ID Numbers: 1902G1721

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No