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

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

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.

Study Overview

• Status: Completed
• Conditions: Ileus
• Intervention / Treatment: Drug: MOA-728; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 374
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide SA, Australia, 5006
  • Elizabeth Vale SA, Australia, 5112
• Belgium
  • Edegem
    • Wilrijkstraat 10, Edegem, Belgium, 2650
  • Gent Belgium
    • De Pintelaan 185, Gent Belgium, Belgium, 9000
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
• Germany
  • Heidelberg, Germany, 110 69120
  • Berlin
    • Augustenburger Platz 1, Berlin, Germany, 13353 DEU
  • Muenchen
    • Nussbaumstrasse 20, Muenchen, Germany, 80336 DEU
• Hungary
  • Nyiregyhaza, Hungary, 4400
  • Pecs, Hungary, 7624
  • Szekesfehervar, Hungary, 8000
  • Veszprem, Hungary, 8200
• Italy
  • Bergamo, Italy, 24040
  • Ferrara
    • Corso Giovecca 203, Ferrara, Italy, 44100
  • Rome
    • Gemelli, Rome, Italy, 00168
  • Via Giustiniani 2
    • Padova, Via Giustiniani 2, Italy, 35100
• Korea, Republic of
  • Seoul, Korea, Republic of, 135 710
    • Kangnam-Gu
• Netherlands
  • Roosendaal, Netherlands, 4708
  • Amsterdam
    • Jan Toorpstraat 164, Amsterdam, Netherlands, 1061
• Poland
  • Bydgoszcz, Poland, 85-094
  • Lodz
    • Polnocna 42, Lodz, Poland, 91 425
  • Szczecin
    • Powstancow Wielkopolskich 72, Szczecin, Poland, 70-111
• South Africa
  • Moreletapark Pretoria, South Africa, 0044
  • Pretoria, South Africa
  • Pretoria Gauteng, South Africa, 0084
  • Pretoria Gauteng, South Africa, 0181
  • Natal
    • Durban Kwa-Zulu, Natal, South Africa, 3201
  • Western Cape
    • Somerset West, Western Cape, South Africa, 7130
    • Worcester, Western Cape, South Africa, 6850
• United States
  • Arkansas
    • Benton, Arkansas, United States, 72015
  • California
    • Colton, California, United States, 92324
    • Laguna Hills, California, United States, 92653
    • Loma Linda, California, United States, 92354
    • Long Beach, California, United States, 90806
    • Los Angeles, California, United States, 90033
    • Orange, California, United States, 92868
    • San Jose, California, United States, 95124
    • Santa Barbara, California, United States, 93105
  • Colorado
    • Denver, Colorado, United States, 80218
    • Denver, Colorado, United States, 80220
  • Florida
    • Inverness, Florida, United States, 34452
    • Jacksonville, Florida, United States, 32224
    • Jacksonville, Florida, United States, 32216
    • Melbourne, Florida, United States, 32901
    • Miami, Florida, United States, 33136
    • Miami, Florida, United States, 33156
    • Naples, Florida, United States, 34119
    • Orlando, Florida, United States, 32804
    • Pensacola, Florida, United States, 32504
    • Tampa, Florida, United States, 33606
  • Illinois
    • Peoria, Illinois, United States, 61603
  • Iowa
    • Des Moines, Iowa, United States, 50309
  • Kansas
    • Kansas City, Kansas, United States, 66160
  • Kentucky
    • Lexington, Kentucky, United States, 40536
  • Maryland
    • Baltimore, Maryland, United States, 21201
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02118
    • Springfield, Massachusetts, United States, 01199
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5048
    • Detroit, Michigan, United States, 48201
    • Flint, Michigan, United States, 48503
  • Mississippi
    • Jackson, Mississippi, United States, 39202
  • Missouri
    • Columbia, Missouri, United States, 65212
  • Nebraska
    • Omaha, Nebraska, United States, 68131
    • Omaha, Nebraska, United States, 68124
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
  • New York
    • Albany, New York, United States, 12208
    • Bronx, New York, United States, 10467
    • New York, New York, United States, 10016
    • Stony Brook, New York, United States, 11794-8480
    • Syracuse, New York, United States, 13210
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7081
    • Durham, North Carolina, United States, 27710
    • Winston-Salem, North Carolina, United States, 27103
    • Winston-Salem, North Carolina, United States, 27157
  • Ohio
    • Cincinnati, Ohio, United States, 45267
    • Cleveland, Ohio, United States, 44109
    • Columbus, Ohio, United States, 43210
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
  • Oregon
    • Bend, Oregon, United States, 97701
    • Portland, Oregon, United States, 97239
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
    • Philadelphia, Pennsylvania, United States, 19104
    • Philadelphia, Pennsylvania, United States, 19140
    • Philadelphia, Pennsylvania, United States, 19102
    • Philadelphia, Pennsylvania, United States, 19107-5092
    • Pittsburgh, Pennsylvania, United States, 15232
    • Pittsburgh, Pennsylvania, United States, 15213
    • Sellersville, Pennsylvania, United States, 18960
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
  • Tennessee
    • Knoxville, Tennessee, United States, 37934
    • Memphis, Tennessee, United States, 38103
    • Nashville, Tennessee, United States, 37212
  • Texas
    • Fort Worth, Texas, United States, 76135
    • San Antonio, Texas, United States, 78229
    • Temple, Texas, United States, 76508
  • Virginia
    • Norfolk, Virginia, United States, 23507
    • Winchester, Virginia, United States, 22601
  • Washington
    • Bellevue, Washington, United States, 98005
    • Tacoma, Washington, United States, 98405
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53295

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MOA-728 12 mg; 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; MOA-728 will be administered per the dose and schedule specified in the arm.; Other Names: Methylnaltrexone
Experimental: MOA-728 24 mg; 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; MOA-728 will be administered per the dose and schedule specified in the arm.; Other Names: Methylnaltrexone
Placebo Comparator: 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.	Drug: Placebo; Placebo matching to MOA-728 will be administered per the schedule specified in the arm.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Collaborators: Progenics Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2007
• Primary Completion (Actual): February 5, 2008
• Study Completion (Actual): February 5, 2008

Study Registration Dates

• First Submitted: September 11, 2007
• First Submitted That Met QC Criteria: September 11, 2007
• First Posted (Estimate): September 14, 2007

Study Record Updates

• Last Update Posted (Actual): September 4, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Hernia; POI; Ventral Wall Hernia Repair; Post Operative Ileus
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Hernia, Abdominal; Intestinal Obstruction; Hernia; Hernia, Ventral; Ileus; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Methylnaltrexone
• Other Study ID Numbers: 3200L2-301