Trial Outcomes & Findings for A Study Evaluating Intravenous (IV) MOA-728 for the Treatment of Postoperative Ileus (POI) in Participants After Ventral Hernia Repair (NCT NCT00528970)

Last Updated: 2019-09-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

374 participants

Primary outcome timeframe

Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 10

Results posted on

2019-09-04

Participant Flow

Postoperative participants (who had undergone repair of large \[at least 10 centimeters\] ventral hernias, with or without mesh prosthesis via laparotomy or laparoscopy) were randomized in 1:1:1 ratio to either MOA-728 24 mg, MOA-728 12 mg, or placebo treatment groups.

Participants were prospectively stratified by type of surgery (laparotomy or laparoscopy) and geographic region.

Participant milestones

Participant milestones
Measure	MOA-728 12 mg Participants received methylnaltrexone (MOA-728) 12 milligrams (mg) as an intravenous (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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	MOA-728 24 mg Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	Placebo Participants received placebo matched 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.
Overall Study STARTED	124	125	125
Overall Study Received at Least 1 Dose of Study Drug	124	125	124
Overall Study COMPLETED	110	110	105
Overall Study NOT COMPLETED	14	15	20

Reasons for withdrawal

Reasons for withdrawal
Measure	MOA-728 12 mg Participants received methylnaltrexone (MOA-728) 12 milligrams (mg) as an intravenous (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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	MOA-728 24 mg Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	Placebo Participants received placebo matched 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.
Overall Study Adverse Event	6	8	5
Overall Study Lost to Follow-up	0	0	1
Overall Study Other than specified	2	3	3
Overall Study Protocol Violation	2	1	4
Overall Study Lack of Efficacy	0	0	1
Overall Study Withdrawal by Subject	4	3	5
Overall Study Randomized but not treated	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MOA-728 12 mg n=124 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	MOA-728 24 mg n=125 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	Placebo n=124 Participants Participants received placebo matched 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	Total n=373 Participants Total of all reporting groups
Age, Continuous	57.11 years STANDARD_DEVIATION 13.25 • n=5 Participants	55.21 years STANDARD_DEVIATION 13.05 • n=7 Participants	55.82 years STANDARD_DEVIATION 13.52 • n=5 Participants	56.05 years STANDARD_DEVIATION 13.26 • n=4 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	66 Participants n=7 Participants	68 Participants n=5 Participants	197 Participants n=4 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	59 Participants n=7 Participants	56 Participants n=5 Participants	176 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 10

Population: mITT population included all randomized participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	MOA-728 12 mg n=124 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	MOA-728 24 mg n=125 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	Placebo n=124 Participants Participants received placebo matched 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.
Time to First Bowel Movement	93.3 hours Standard Error 3.2	100.4 hours Standard Error 4.2	91.3 hours Standard Error 3.9

SECONDARY outcome

Timeframe: Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 10

Population: mITT population included all randomized participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	MOA-728 12 mg n=124 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	MOA-728 24 mg n=125 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	Placebo n=124 Participants Participants received placebo matched 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.
Time to Discharge Eligibility	44.9 hours Standard Error 2.9	51.4 hours Standard Error 5.1	41.4 hours Standard Error 3.4

SECONDARY outcome

Timeframe: Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 10

Population: mITT population included all randomized participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	MOA-728 12 mg n=124 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	MOA-728 24 mg n=125 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	Placebo n=124 Participants Participants received placebo matched 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.
Time to Discharge Order Written From the End of Surgery	130.6 hours Standard Error 15.52	123.8 hours Standard Error 6.8	132.9 hours Standard Error 14.1

SECONDARY outcome

Timeframe: Day 2

Population: mITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	MOA-728 12 mg n=115 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	MOA-728 24 mg n=113 Participants Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	Placebo n=113 Participants Participants received placebo matched 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.
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)	10 Participants	19 Participants	7 Participants

Adverse Events

MOA-728 12 mg

Serious events: 20 serious events

Other events: 68 other events

Deaths: 0 deaths

MOA-728 24 mg

Serious events: 17 serious events

Other events: 71 other events

Deaths: 0 deaths

Placebo

Serious events: 28 serious events

Other events: 73 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	MOA-728 12 mg n=124 participants at risk Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	MOA-728 24 mg n=125 participants at risk Participants received 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.	Placebo n=124 participants at risk Participants received placebo matched 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 was administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple was placed in the participant). Dose administration was continued for a maximum of 10 days.
Cardiac disorders Tachycardia	3.2% 4/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 2/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	6.5% 8/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	8.1% 10/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	10.4% 13/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	8.9% 11/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	31.5% 39/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	26.4% 33/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	30.6% 38/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	12.9% 16/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	16.0% 20/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	16.9% 21/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Fatigue	5.6% 7/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	0.80% 1/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	2.4% 3/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Pyrexia	13.7% 17/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	12.0% 15/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	14.5% 18/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	3.2% 4/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	8.0% 10/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	3.2% 4/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	5.6% 7/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	3.2% 4/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	4.0% 5/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	6.5% 8/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	7.2% 9/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	10.5% 13/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Somnolence	5.6% 7/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	0.80% 1/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	4.8% 6/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary retention	9.7% 12/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	8.0% 10/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	8.9% 11/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	13.7% 17/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	8.8% 11/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	13.7% 17/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	3.2% 4/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	6.4% 8/125 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.	5.6% 7/124 • Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15 Safety population included all randomized participants who received at least 1 dose of study drug.

Additional Information

Director of Clinical Operations

Bausch Health Americas, Inc

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Please contact Sponsor directly for additional information.
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Restriction type: OTHER