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

• Sponsor: Bausch Health Americas, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00528970
• Collaborator: Progenics Pharmaceuticals, Inc. (Industry)
• Enrollment: 374
• Locations: 106
• Arms: 3
• Actual Duration (Months): 3.6
• Patients Per Site: 3.5
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ileus	Drug: MOA-728; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 374 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Oct 17, 2007
• Actual Primary Completion Date: Feb 5, 2008
• Actual Study Completion Date: Feb 5, 2008

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Benton	Arkansas	United States	72015
2		Colton	California	United States	92324
3		Laguna Hills	California	United States	92653
4		Loma Linda	California	United States	92354
5		Long Beach	California	United States	90806
6		Los Angeles	California	United States	90033
7		Orange	California	United States	92868
8		San Jose	California	United States	95124
9		Santa Barbara	California	United States	93105
10		Denver	Colorado	United States	80218
11		Denver	Colorado	United States	80220
12		Inverness	Florida	United States	34452
13		Jacksonville	Florida	United States	32216
14		Jacksonville	Florida	United States	32224
15		Melbourne	Florida	United States	32901
16		Miami	Florida	United States	33136
17		Miami	Florida	United States	33156
18		Naples	Florida	United States	34119
19		Orlando	Florida	United States	32804
20		Pensacola	Florida	United States	32504
21		Tampa	Florida	United States	33606
22		Peoria	Illinois	United States	61603
23		Des Moines	Iowa	United States	50309
24		Kansas City	Kansas	United States	66160
25		Lexington	Kentucky	United States	40536
26		Baltimore	Maryland	United States	21201
27		Boston	Massachusetts	United States	02118
28		Boston	Massachusetts	United States	02215
29		Springfield	Massachusetts	United States	01199
30		Ann Arbor	Michigan	United States	48109-5048
31		Detroit	Michigan	United States	48201
32		Flint	Michigan	United States	48503
33		Jackson	Mississippi	United States	39202
34		Columbia	Missouri	United States	65212
35		Omaha	Nebraska	United States	68124
36		Omaha	Nebraska	United States	68131
37		New Brunswick	New Jersey	United States	08903
38		Albuquerque	New Mexico	United States	87106
39		Albany	New York	United States	12208
40		Bronx	New York	United States	10467
41		New York	New York	United States	10016
42		Stony Brook	New York	United States	11794-8480
43		Syracuse	New York	United States	13210
44		Chapel Hill	North Carolina	United States	27599-7081
45		Durham	North Carolina	United States	27710
46		Winston-Salem	North Carolina	United States	27103
47		Winston-Salem	North Carolina	United States	27157
48		Cincinnati	Ohio	United States	45267
49		Cleveland	Ohio	United States	44109
50		Columbus	Ohio	United States	43210
51		Oklahoma City	Oklahoma	United States	73104
52		Bend	Oregon	United States	97701
53		Portland	Oregon	United States	97239
54		Hershey	Pennsylvania	United States	17033
55		Philadelphia	Pennsylvania	United States	19102
56		Philadelphia	Pennsylvania	United States	19104
57		Philadelphia	Pennsylvania	United States	19107-5092
58		Philadelphia	Pennsylvania	United States	19140
59		Pittsburgh	Pennsylvania	United States	15213
60		Pittsburgh	Pennsylvania	United States	15232
61		Sellersville	Pennsylvania	United States	18960
62		Providence	Rhode Island	United States	02906
63		Sioux Falls	South Dakota	United States	57105
64		Knoxville	Tennessee	United States	37934
65		Memphis	Tennessee	United States	38103
66		Nashville	Tennessee	United States	37212
67		Fort Worth	Texas	United States	76135
68		San Antonio	Texas	United States	78229
69		Temple	Texas	United States	76508
70		Norfolk	Virginia	United States	23507
71		Winchester	Virginia	United States	22601
72		Bellevue	Washington	United States	98005
73		Tacoma	Washington	United States	98405
74		Morgantown	West Virginia	United States	26506
75		Milwaukee	Wisconsin	United States	53295
76		Adelaide SA		Australia	5006
77		Elizabeth Vale SA		Australia	5112
78		Wilrijkstraat 10	Edegem	Belgium	2650
79		De Pintelaan 185	Gent Belgium	Belgium	9000
80		Edmonton	Alberta	Canada	T6G 2G3
81		Vancouver	British Columbia	Canada	V6Z 1Y6
82		Montreal	Quebec	Canada	H3T 1E2
83		Augustenburger Platz 1	Berlin	Germany	13353 DEU
84		Nussbaumstrasse 20	Muenchen	Germany	80336 DEU
85		Heidelberg		Germany	110 69120
86		Nyiregyhaza		Hungary	4400
87		Pecs		Hungary	7624
88		Szekesfehervar		Hungary	8000
89		Veszprem		Hungary	8200
90		Corso Giovecca 203	Ferrara	Italy	44100
91		Gemelli	Rome	Italy	00168
92		Padova	Via Giustiniani 2	Italy	35100
93		Bergamo		Italy	24040
94	Kangnam-Gu	Seoul		Korea, Republic of	135 710
95		Jan Toorpstraat 164	Amsterdam	Netherlands	1061
96		Roosendaal		Netherlands	4708
97		Polnocna 42	Lodz	Poland	91 425
98		Powstancow Wielkopolskich 72	Szczecin	Poland	70-111
99		Bydgoszcz		Poland	85-094
100		Durban Kwa-Zulu	Natal	South Africa	3201
101		Somerset West	Western Cape	South Africa	7130
102		Worcester	Western Cape	South Africa	6850
103		Moreletapark Pretoria		South Africa	0044
104		Pretoria Gauteng		South Africa	0084
105		Pretoria Gauteng		South Africa	0181
106		Pretoria		South Africa

Sponsors and Collaborators

• Bausch Health Americas, Inc.
• Progenics Pharmaceuticals, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch Health Americas, Inc.
• ClinicalTrials.gov Identifier: NCT00528970
• Other Study ID Numbers: 3200L2-301
• First Posted: Sep 14, 2007
• Last Update Posted: Sep 4, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Bausch Health Americas, Inc.: POI; Hernia; Ventral Wall Hernia Repair; Post Operative Ileus
• Additional relevant MeSH terms: Ileus; Hernia; Hernia, Ventral; Methylnaltrexone

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	Participants were prospectively stratified by type of surgery (laparotomy or laparoscopy) and geographic region.

Arm/Group Title	MOA-728 12 mg	MOA-728 24 mg	Placebo
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	124	125	125
Received at Least 1 Dose of Study Drug	124	125	124
COMPLETED	110	110	105
NOT COMPLETED	14	15	20

Baseline Characteristics

Arm/Group Title	MOA-728 12 mg	MOA-728 24 mg	Placebo	Total
Arm/Group Description	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.	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.	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 of all reporting groups
Overall Participants	124	125	124	373
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.11 (13.25)	55.21 (13.05)	55.82 (13.52)	56.05 (13.26)
Sex: Female, Male (Count of Participants)
Female	63 50.8%	66 52.8%	68 54.8%	197 52.8%
Male	61 49.2%	59 47.2%	56 45.2%	176 47.2%

Outcome Measures

1. Primary Outcome

Title	Time to First Bowel Movement
Description	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.
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MOA-728 12 mg	MOA-728 24 mg	Placebo
Arm/Group Description	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.	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.	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.
Measure Participants	124	125	124
Mean (Standard Error) [hours]	93.3 (3.2)	100.4 (4.2)	91.3 (3.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MOA-728 12 mg, Placebo
	Comments	Analysis was performed using log-rank test stratified by surgery type and region for comparisons of survival distributions for active MOA versus Placebo group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.944
	Comments	Threshold for significance at 0.05 level.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.0
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MOA-728 24 mg, Placebo
	Comments	Analysis was performed using log-rank test stratified by surgery type and region for comparisons of survival distributions for active MOA versus Placebo group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.208
	Comments	Threshold for significance at 0.05 level.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.1
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MOA-728 12 mg	MOA-728 24 mg	Placebo
Arm/Group Description	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.	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.	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.
Measure Participants	124	125	124
Mean (Standard Error) [hours]	44.9 (2.9)	51.4 (5.1)	41.4 (3.4)

3. Secondary Outcome

Title	Time to Discharge Order Written From the End of Surgery
Description	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.
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MOA-728 12 mg	MOA-728 24 mg	Placebo
Arm/Group Description	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.	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.	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.
Measure Participants	124	125	124
Mean (Standard Error) [hours]	130.6 (15.52)	123.8 (6.8)	132.9 (14.1)

4. Secondary Outcome

Title	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)
Description	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.
Time Frame	Day 2

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MOA-728 12 mg	MOA-728 24 mg	Placebo
Arm/Group Description	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.	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.	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.
Measure Participants	115	113	113
Count of Participants [Participants]	10 8.1%	19 15.2%	7 5.6%

Adverse Events

Time Frame	Day 1 (From the time of end of surgery [that is; from the first dose of study drug administration]) up to Day 15
Adverse Event Reporting Description	Safety population included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title	MOA-728 12 mg		MOA-728 24 mg		Placebo
Arm/Group Description	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.		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.		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.
All Cause Mortality
	MOA-728 12 mg		MOA-728 24 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MOA-728 12 mg		MOA-728 24 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/124 (16.1%)		17/125 (13.6%)		28/124 (22.6%)
Blood and lymphatic system disorders
Anaemia	0/124 (0%)		0/125 (0%)		2/124 (1.6%)
Coagulopathy	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Cardiac disorders
Supraventricular tachycardia	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Tachycardia	0/124 (0%)		1/125 (0.8%)		1/124 (0.8%)
Gastrointestinal disorders
Abdominal hernia	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Abdominal pain	1/124 (0.8%)		1/125 (0.8%)		1/124 (0.8%)
Abdominal pain upper	0/124 (0%)		1/125 (0.8%)		0/124 (0%)
Abdominal wall haematoma	0/124 (0%)		1/125 (0.8%)		0/124 (0%)
Diarrhoea	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Enterocutaneous fistula	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Gastritis	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Intestinal fistula	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Intestinal obstruction	0/124 (0%)		1/125 (0.8%)		0/124 (0%)
Localised intraabdominal fluid collection	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Nausea	0/124 (0%)		2/125 (1.6%)		0/124 (0%)
Small intestinal obstruction	0/124 (0%)		1/125 (0.8%)		1/124 (0.8%)
Vomiting	0/124 (0%)		1/125 (0.8%)		0/124 (0%)
General disorders
Death	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Hernia	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Pyrexia	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Wound necrosis	0/124 (0%)		1/125 (0.8%)		1/124 (0.8%)
Hepatobiliary disorders
Cholelithiasis	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Jaundice cholestatic	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Infections and infestations
Bacteraemia	0/124 (0%)		1/125 (0.8%)		0/124 (0%)
Cellulitis	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Device related infection	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Gastroenteritis	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Incision site infection	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Klebsiella bacteraemia	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Pneumonia	0/124 (0%)		1/125 (0.8%)		0/124 (0%)
Post procedural infection	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Urinary tract infection	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Wound infection	5/124 (4%)		0/125 (0%)		2/124 (1.6%)
Wound infection staphylococcal	1/124 (0.8%)		2/125 (1.6%)		0/124 (0%)
Injury, poisoning and procedural complications
Incisional hernia, obstructive	0/124 (0%)		1/125 (0.8%)		0/124 (0%)
Postoperative ileus	3/124 (2.4%)		1/125 (0.8%)		2/124 (1.6%)
Postoperative wound complication	1/124 (0.8%)		1/125 (0.8%)		0/124 (0%)
Seroma	0/124 (0%)		1/125 (0.8%)		2/124 (1.6%)
Wound dehiscence	0/124 (0%)		0/125 (0%)		3/124 (2.4%)
Wound secretion	1/124 (0.8%)		0/125 (0%)		1/124 (0.8%)
Investigations
Liver function test abnormal	0/124 (0%)		1/125 (0.8%)		1/124 (0.8%)
Metabolism and nutrition disorders
Dehydration	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Nervous system disorders
Transient ischaemic attack	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/124 (0.8%)		0/125 (0%)		1/124 (0.8%)
Dyspnoea	0/124 (0%)		1/125 (0.8%)		0/124 (0%)
Pneumonia aspiration	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Pulmonary embolism	0/124 (0%)		1/125 (0.8%)		2/124 (1.6%)
Pulmonary oedema	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Respiratory failure	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Skin and subcutaneous tissue disorders
Skin necrosis	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Vascular disorders
Deep vein thrombosis	0/124 (0%)		0/125 (0%)		1/124 (0.8%)
Hypotension	1/124 (0.8%)		0/125 (0%)		0/124 (0%)
Other (Not Including Serious) Adverse Events
	MOA-728 12 mg		MOA-728 24 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/124 (54.8%)		71/125 (56.8%)		73/124 (58.9%)
Cardiac disorders
Tachycardia	4/124 (3.2%)		2/125 (1.6%)		8/124 (6.5%)
Gastrointestinal disorders
Constipation	10/124 (8.1%)		13/125 (10.4%)		11/124 (8.9%)
Nausea	39/124 (31.5%)		33/125 (26.4%)		38/124 (30.6%)
Vomiting	16/124 (12.9%)		20/125 (16%)		21/124 (16.9%)
General disorders
Fatigue	7/124 (5.6%)		1/125 (0.8%)		3/124 (2.4%)
Pyrexia	17/124 (13.7%)		15/125 (12%)		18/124 (14.5%)
Metabolism and nutrition disorders
Hypokalaemia	4/124 (3.2%)		10/125 (8%)		4/124 (3.2%)
Nervous system disorders
Dizziness	7/124 (5.6%)		4/125 (3.2%)		5/124 (4%)
Headache	8/124 (6.5%)		9/125 (7.2%)		13/124 (10.5%)
Somnolence	7/124 (5.6%)		1/125 (0.8%)		6/124 (4.8%)
Renal and urinary disorders
Urinary retention	12/124 (9.7%)		10/125 (8%)		11/124 (8.9%)
Skin and subcutaneous tissue disorders
Pruritus	17/124 (13.7%)		11/125 (8.8%)		17/124 (13.7%)
Vascular disorders
Hypertension	4/124 (3.2%)		8/125 (6.4%)		7/124 (5.6%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

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