A Study Evaluating Intravenous (IV) MOA-728 for the Treatment of Postoperative Ileus (POI) in Participants After Ventral Hernia Repair

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of two different dose regimens (12 milligrams [mg] and 24 mg) of IV MOA-728 versus placebo in shortening the time to return of bowel function in participants receiving opioid analgesia administered via patient-controlled anesthesia (PCA), and who had undergone repair of large (greater than or equal to [≥]10 centimeters) ventral hernias with or without a mesh prosthesis via laparotomy or laparoscopy.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Intravenous Methylnaltrexone (MOA-728) for the Treatment of Post Operative Ileus After Ventral Hernia Repair

Conditions
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Ileus

Intervention / Treatment
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* Drug: MOA-728
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, ages 18 and older. Scheduled for ventral wall hernia repair with general anesthesia. Meets the American Society of Anesthesiologists physical status I, II, or III. Exclusion Criteria: Received investigational drug or procedure within 30 days of randomization. Women who are pregnant or lactating. Calculated creatinine clearance (Cockcroft-Gault glomerular filtration rate [GFR] formula) less than or equal to (</=) 50 milliliters/minute (mL/min).

Ages Eligible for Study
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Minimum Age: 18 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: MOA-728 12 mg<br>Participants will receive methylnaltrexone (MOA-728) 12 mg as an IV infusion over approximately 20 minutes for approximately every 6 hours for a total of 4 doses in 24-hour period. The first dose of study drug will be administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple is placed in the participant). Dose administration will be continued for a maximum of 10 days. | Drug: MOA-728<br>* MOA-728 will be administered per the dose and schedule specified in the arm.<br>* Other names: Methylnaltrexone;|
| Experimental: MOA-728 24 mg<br>Participants will receive MOA-728 24 mg as an IV infusion over approximately 20 minutes for approximately every 6 hours for a total of 4 doses in 24-hour period. The first dose of study drug will be administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple is placed in the participant). Dose administration will be continued for a maximum of 10 days. | Drug: MOA-728<br>* MOA-728 will be administered per the dose and schedule specified in the arm.<br>* Other names: Methylnaltrexone;|
| Placebo Comparator: Placebo<br>Participants will receive placebo matching to MOA-728 as an IV infusion over approximately 20 minutes for approximately every 6 hours for a total of 4 doses in 24-hour period. The first dose of study drug will be administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple is placed in the participant). Dose administration will be continued for a maximum of 10 days. | Drug: Placebo<br>* Placebo matching to MOA-728 will be administered per the schedule specified in the arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Bowel Movement | Time to first bowel movement was measured from the end of surgery (defined as the time when the last skin suture or staple was placed in the participant). Time of the first bowel movement was recorded on the electronic case report form (eCRF). The first bowel movement was defined as a normal stool for a postoperative participant based on the clinical judgment of the investigator or designee. Analysis was performed by Kaplan-Meier estimate. Participants who had a bowel movement but were readmitted to the hospital within 1 week after discharge with a diagnosis of postoperative ileus (POI) were considered censored at the time of the first bowel movement as if the bowel movement had not occurred. | Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Discharge Eligibility | Time to discharge eligibility was measured from the end of surgery (defined as the time when the last skin suture or staple was placed in the participant). Discharge eligibility was defined as tolerance of oral intake of liquids greater than (>) 500 milliliters (mL) per 8 hours without nausea or retching/vomiting. Analysis was performed by Kaplan-Meier estimate. | Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 10 | 
| Time to Discharge Order Written From the End of Surgery | The investigator or designee recorded the time of the order. Participants re-admitted to the hospital with a diagnosis of POI within 7 days after discharge was considered treatment failures. Analysis was performed by Kaplan-Meier estimate. | Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 10 | 
| Number of Participants With Clinically Meaningful Events (CMEs) for Nausea or Retching/Vomiting at Day 2 (24 Hours) as Evaluated by the Opioid-Related Symptom Distress Scale (SDS) | CMEs were defined using opioid-related SDS (assessed participant-reported levels of severity concerning 10 symptoms associated with opioid medication usage: fatigue, drowsiness, inability to concentrate, nausea, dizziness, constipation, itching, difficulty with urination, confusion and retching/vomiting). CME = any symptom rated as severe (3) or very severe (4), with the exception of confusion. A total CME score was calculated by summing the number of CMEs across symptoms and ranged from 0 to 9. CME was counted for either nausea or vomiting/retching, or both and reported in this outcome measure. | Day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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POI, Hernia, Ventral Wall Hernia Repair, Post Operative Ileus