Study of Intravenous (IV) Methylnaltrexone Bromide (MNTX) in the Treatment of Post-Operative Ileus (POI)

Phase 3

Completed

Conditions: Post-Operative Ileus (POI)

Interventions: Drug: Placebo
Drug: Methylnaltrexone

Registration Number: NCT00401375

Lead Sponsor: Bausch Health Americas, Inc.

Brief Summary: To evaluate the safety and efficacy of MNTX in participants who have undergone segmental colectomy and to assess if the time between the end of surgery and the first bowel movement is significantly shorter in the MNTX regimen than the equivalent assessment using a placebo regimen.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 524

Inclusion Criteria

Male and female participants at least 18 years of age.
All participants must meet American Society of Anesthesiologists (ASA) physical status I, II, or III.
Participants must sign an informed consent form (ICF).
Participants must be scheduled for a segmental colectomy via open laparotomy with general anesthesia.
Females of childbearing potential must have a negative serum pregnancy test at the screening visit.
Negative for history of chronic active hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection.

Exclusion Criteria

Participants who received any investigational new drug in the 30 days prior to screening visit.
Females who are pregnant or lactating.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive placebo matching to MNTX as an IV infusion over approximately 20 minutes for every 6 hours until one of the following occurs: 1) 24 hours elapsed after the first bowel movement and the participant was tolerating clear liquids, 2) the participant was discharged from the hospital, or 3) a maximum of 10 days elapsed. The first dose of study drug will be administered within the first 90 minutes after the end of surgery (defined as the time when the last skin suture or staple is placed in the participant).
MNTX 24 mg	Methylnaltrexone	Participants will receive MNTX 24 mg as an IV infusion over approximately 20 minutes for every 6 hours until one of the following occurs: 1) 24 hours elapsed after the first bowel movement and the participant was tolerating clear liquids, 2) the participant was discharged from the hospital, or 3) a maximum of 10 days elapsed. The first dose of study drug will be administered within the first 90 minutes after the end of surgery (defined as the time when the last skin suture or staple is placed in the participant).
MNTX 12 mg	Methylnaltrexone	Participants will receive methylnaltrexone (MNTX) 12 milligrams (mg) as an intravenous (IV) infusion over approximately 20 minutes for every 6 hours until one of the following occurs: 1) 24 hours elapsed after the first bowel movement and the participant was tolerating clear liquids, 2) the participant was discharged from the hospital, or 3) a maximum of 10 days elapsed. The first dose of study drug will be administered within the first 90 minutes after the end of surgery (defined as the time when the last skin suture or staple is placed in the participant).

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 both tolerance of solid food and at least one bowel movement. Participants were considered to have tolerated solid food when they have eaten greater than or equal to (≥) 50 percent (%), of the first of two successive solid food meals (based on the judgement of the investigator or designee), without vomiting or nausea. Participants readmitted to the hospital with a diagnosis of POI within 7 days of discharge were considered treatment failures. 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 were considered treatment failures. Analysis was performed by Kaplan-Meier estimate.
Number of Participants With Clinically Meaningful Events (CMEs) for Nausea or Retching/Vomiting at 0 or 24 Hours as Evaluated by the Opioid-Related Symptom Distress Scale (SDS)	0 and 24 hours	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.