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

• ClinicalTrials.gov Identifier: NCT00401375
• Recruitment Status: Completed
• First Posted: November 20, 2006
• Results First Posted: September 4, 2019
• Last Update Posted: September 4, 2019
• Sponsor: Bausch Health Americas, Inc.
• Collaborator: Wyeth is now a wholly owned subsidiary of Pfizer
• Information provided by (Responsible Party): Bausch Health Americas, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Post-Operative Ileus (POI)	Drug: Methylnaltrexone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 524 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Study of Intravenous (IV) Methylnaltrexone Bromide (MNTX) in the Treatment of Post-Operative Ileus (POI)
• Actual Study Start Date: October 31, 2006
• Actual Primary Completion Date: February 29, 2008
• Actual Study Completion Date: February 29, 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: MNTX 12 mg; 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).	Drug: Methylnaltrexone; Methylnaltrexone will be administered as per the dose and schedule specified in the respective arms.; Other Name: MNTX
Experimental: MNTX 24 mg; 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).	Drug: Methylnaltrexone; Methylnaltrexone will be administered as per the dose and schedule specified in the respective arms.; Other Name: MNTX
Placebo Comparator: 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).	Drug: Placebo; Placebo matching to methylnaltrexone will be administered as per the schedule specified in the respective arm.

Outcome Measures

Primary Outcome Measures :

1. Time to First Bowel Movement [ Time Frame: 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 :

1. Time to Discharge Eligibility [ Time Frame: 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.
2. Time to Discharge Order Written From the End of Surgery [ Time Frame: 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.
3. 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) [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, New York

Progenics Pharmaceuticals

Tarrytown, New York, United States, 10591

Sponsors and Collaborators

Bausch Health Americas, Inc.

Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Lindsey Mathew; Bausch Health Americas, Inc.

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yu CS, Chun HK, Stambler N, Carpenito J, Schulman S, Tzanis E, Randazzo B. Safety and efficacy of methylnaltrexone in shortening the duration of postoperative ileus following segmental colectomy: results of two randomized, placebo-controlled phase 3 trials. Dis Colon Rectum. 2011 May;54(5):570-8. doi: 10.1007/DCR.0b013e3182092bde.

• Responsible Party: Bausch Health Americas, Inc.
• ClinicalTrials.gov Identifier: NCT00401375
• Other Study ID Numbers: MNTX 3301
• First Posted: November 20, 2006
• Results First Posted: September 4, 2019
• Last Update Posted: September 4, 2019
• Last Verified: August 2019

Additional relevant MeSH terms:

Ileus; Intestinal Obstruction; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Methylnaltrexone; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents