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

Phase 3

Completed

Conditions: Ileus

Interventions: Drug: MOA-728
Drug: Placebo

Registration Number: NCT00528970

Lead Sponsor: Bausch Health Americas, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 374

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MOA-728 24 mg	MOA-728	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.
Placebo	Placebo	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.
MOA-728 12 mg	MOA-728	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.

Primary Outcome Measures

Name	Time	Method
Time to First Bowel Movement	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 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.

Secondary Outcome Measures

Name	Time	Method
Time to Discharge Eligibility	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 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.
Time to Discharge Order Written From the End of Surgery	Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 10	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.
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)	Day 2	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.