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

Study Overview
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Brief Summary
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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.

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

Conditions
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Postoperative Gastrointestinal Dysfunction

Intervention / Treatment
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* Drug: Naldemedine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naldemedine 1.25 mg<br>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<br>* Oral tablet<br>* Other names: S-297995;|
| Experimental: Naldemedine 2.5 mg<br>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<br>* Oral tablet<br>* Other names: S-297995;|
| Experimental: Naldemedine 5 mg<br>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<br>* Oral tablet<br>* Other names: S-297995;|
| Placebo Comparator: Placebo<br>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<br>* Oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastrointestinal recovery, peripherally acting mu-opioid receptor antagonist, Bowel resection, Bowel transection