A Study of Alvimopan for the Management of Postoperative Ileus in Participants Undergoing Radical Cystectomy

Time to achieve recovery of gastrointestinal (GI) function as measured by a composite endpoint of both upper GI recovery (toleration of solid food) and lower GI recovery (first bowel movement \[BM\]) using KM Estimates and Cox PH Model. This endpoint was referred to as GI2. GI2 was calculated as GI2 = maximum (max) (solids, BM). The KM estimate reported below is biased because of the censoring of the last observation. Censoring Rules for Study Participants who: Completed: the censored time for the event was determined as: censored time = minimum \[maximum (time of/to last GI assessment, time of/to hospital discharge order written), study duration\]. Discontinued: censored time = maximum (time of/to last GI assessment, time of/to discontinuation)

Time frame: From day of surgery (Day 0) up to 10 days in hospital

Population: All participants who received at least 1 dose of study medication, who had at least 1 postdose GI assessment, who had the protocol-specified surgery, and had evaluable time to achieve G12 data. 39 participants in the Placebo group and 17 participants in the Alvimopan group were censored.

The KM estimate reported below is biased because of the censoring of the last observation. Censoring Rules for Study Participants who: Completed: the censored time for the event was determined as: censored time = minimum \[maximum (time of/to last GI assessment, time of/to hospital discharge order written), study duration\]. Discontinued: censored time = maximum (time of/to last GI assessment, time of/to discontinuation)

Time frame: Day of surgery (Day 0) up to 10 days in hospital

Population: All participants who received at least 1 dose of study medication, who had at least 1 postdose GI assessment, who had the protocol-specified surgery, and had evaluable time to DOW data. 36 participants in the Placebo group and 15 participants in the Alvimopan group were censored.

The endpoint of time to ready for discharge was based solely on the recovery of GI function as determined by the surgeon. The KM estimate reported below is biased because of the censoring of the last observation. Censoring Rules for Study Participants who: Completed: the censored time for the event was determined as: censored time = minimum \[maximum (time of/to last GI assessment, time of/to hospital discharge order written), study duration\]. Discontinued: censored time = maximum (time of/to last GI assessment, time of/to discontinuation)

Time frame: Day of surgery (Day 0) up to 10 days in hospital

Population: All participants who received at least 1 dose of study medication, who had at least 1 postdose GI assessment, who had the protocol-specified surgery, and had evaluable ready to discharge data. 21 participants in the Placebo group and 12 participants in the Alvimopan group were censored.

DOW responders were defined as those participants who met all the following criteria: achieved DOW by the cutoff point, did not have hospital stay prolonged because of POI, and did not have readmission for POI within 7 days of actual hospital discharge. PSD were measured in 24 hour increments after surgery.

Time frame: Day of surgery (Day 0) through PSD 3, PSD 4, PSD 5, PSD 6, and PSD 7

Population: All participants who received at least 1 dose of study medication, who had at least 1 postdose GI assessment, who had the protocol-specified surgery, and had evaluable time to achieve G12 data.

Time to achieve recovery of GI function was measured by a composite endpoint of time to first BM and time to tolerate first solid food (solids). This endpoint was referred to as GI2, and GI2 was calculated as follows: GI2 = max (solids, BM). GI2 responders were defined as those participants who met all the following criteria: achieved GI2 by the cutoff point, did not have hospital stay prolonged because of POI, and did not have readmission for POI within 7 days of actual hospital discharge. Postsurgery Days (PSD) were measured in 24 hour increments after surgery.

Time frame: Day of surgery (Day 0) through PSD 3, PSD 4, PSD 5, PSD 6, and PSD 7

Population: All participants who received at least 1 dose of study medication, who had at least 1 postdose GI assessment, who had the protocol-specified surgery, and had evaluable time to achieve G12 data.

A participant was considered a postoperative LOS responder if the postoperative LOS was less than or equal to 7 days. The postoperative LOS for a participant was calculated as follows: (date of DOW) - (date of surgery). Participants with missing data were considered nonresponders.

Time frame: Day of surgery (Day 0) up to 7 days after surgery

Population: All participants who received at least 1 dose of study medication, who had at least 1 postdose GI assessment, who had the protocol-specified surgery, and had evaluable postoperative LOS data.

CV events of interest included congestive heart failure, CV death, cerebrovascular accident, myocardial infarction, serious arrhythmia, and unstable angina. CV events were adjudicated by a blinded external committee.

Time frame: Baseline to 30 days post discharge

Population: All participants who received at least 1 dose of study medication.

POM was defined as the need for postoperative nasogastric (NG) tube insertion, hospital stay prolonged because of postoperative ileus (POI) (as determined by the investigator), or readmission (readmiss) to the hospital (hosp) for POI within 7 days (d) after discharge.

Time frame: During hospitalization or within 7 days after discharge

Population: All participants who received at least 1 dose of study medication, who had at least 1 postdose GI assessment, who had the protocol-specified surgery, and had evaluable POM data.

The postoperative LOS was determined by the difference between the date of hospital DOW and the date of surgery; that is, the postoperative LOS for a participant was calculated as follows: (date of DOW) - (date of surgery).

Time frame: Day of surgery (Day 0) to the day of hospital DOW

Population: All participants who received at least 1 dose of study medication, who had at least 1 postdose GI assessment, who had the protocol-specified surgery, and had evaluable postoperative LOS data.