Trial Outcomes & Findings for A Study of TAK-954 to Treat Gastrointestinal Dysfunction in Adults After Surgery (NCT NCT03827655)

Last Updated: 2023-06-23

Results Overview

The time from end of surgery to tolerance of solid food, without first occurrence of vomiting or clinically significant nausea for 1 calendar day after a solid meal (upper GI function) and first spontaneous bowel movement (lower GI function), whichever occurred later up to 10 days postsurgery was observed. Kaplan-Meier survival analysis method was used.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

209 participants

Primary outcome timeframe

Day 1 (surgery) up to Day 10 postsurgery

Results posted on

2023-06-23

Participant Flow

Participants took part in the study at 20 investigative sites in Germany and the United States from 07 March 2019 to 27 May 2022.

Participants with a diagnosis of postoperative gastrointestinal dysfunction were enrolled in a 1:1:1:1:1 ratio into one of the five treatment groups to receive TAK-954 and/or placebo before and after surgery.

Participant milestones

Participant milestones
Measure	TAK-954 0.5 mg/100 mL + Placebo TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	Placebo TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once presurgery on Day 1 and once daily postsurgery until return of upper and lower gastrointestinal (GI) function or for up to 10 days.	TAK-954 0.1 mg/100 mL TAK-954 0.1 milligrams per 100 milliliters (mg/100 mL), 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Overall Study STARTED	52	52	27	51	27
Overall Study Safety Set	50	49	26	48	25
Overall Study Full Analysis Set (FAS)	44	45	23	42	21
Overall Study Pharmacokinetic (PK) Analysis Set	50	0	26	47	24
Overall Study COMPLETED	49	45	24	47	25
Overall Study NOT COMPLETED	3	7	3	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	TAK-954 0.5 mg/100 mL + Placebo TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	Placebo TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once presurgery on Day 1 and once daily postsurgery until return of upper and lower gastrointestinal (GI) function or for up to 10 days.	TAK-954 0.1 mg/100 mL TAK-954 0.1 milligrams per 100 milliliters (mg/100 mL), 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Overall Study Death	1	0	0	0	0
Overall Study Protocol Deviation	0	1	0	1	1
Overall Study Withdrawal by Subject	1	3	2	2	0
Overall Study Reason not Specified	1	3	1	1	1

Baseline Characteristics

Number analyzed is the number of participants with data available for analysis at Baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=52 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=27 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=51 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=27 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=52 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	Total n=209 Participants Total of all reporting groups
Age, Continuous	57.9 years STANDARD_DEVIATION 11.99 • n=52 Participants	55.9 years STANDARD_DEVIATION 13.83 • n=27 Participants	57.3 years STANDARD_DEVIATION 14.10 • n=51 Participants	53.7 years STANDARD_DEVIATION 12.15 • n=27 Participants	53.2 years STANDARD_DEVIATION 15.28 • n=52 Participants	55.8 years STANDARD_DEVIATION 13.66 • n=209 Participants
Sex: Female, Male Female	32 Participants n=52 Participants	10 Participants n=27 Participants	21 Participants n=51 Participants	12 Participants n=27 Participants	26 Participants n=52 Participants	101 Participants n=209 Participants
Sex: Female, Male Male	20 Participants n=52 Participants	17 Participants n=27 Participants	30 Participants n=51 Participants	15 Participants n=27 Participants	26 Participants n=52 Participants	108 Participants n=209 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=52 Participants	1 Participants n=27 Participants	3 Participants n=51 Participants	2 Participants n=27 Participants	3 Participants n=52 Participants	10 Participants n=209 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=52 Participants	21 Participants n=27 Participants	37 Participants n=51 Participants	21 Participants n=27 Participants	39 Participants n=52 Participants	161 Participants n=209 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=52 Participants	5 Participants n=27 Participants	11 Participants n=51 Participants	4 Participants n=27 Participants	10 Participants n=52 Participants	38 Participants n=209 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=52 Participants	0 Participants n=27 Participants	0 Participants n=51 Participants	0 Participants n=27 Participants	0 Participants n=52 Participants	1 Participants n=209 Participants
Race (NIH/OMB) Asian	1 Participants n=52 Participants	1 Participants n=27 Participants	0 Participants n=51 Participants	0 Participants n=27 Participants	0 Participants n=52 Participants	2 Participants n=209 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=52 Participants	1 Participants n=27 Participants	0 Participants n=51 Participants	0 Participants n=27 Participants	0 Participants n=52 Participants	1 Participants n=209 Participants
Race (NIH/OMB) Black or African American	5 Participants n=52 Participants	2 Participants n=27 Participants	0 Participants n=51 Participants	4 Participants n=27 Participants	3 Participants n=52 Participants	14 Participants n=209 Participants
Race (NIH/OMB) White	37 Participants n=52 Participants	18 Participants n=27 Participants	42 Participants n=51 Participants	18 Participants n=27 Participants	38 Participants n=52 Participants	153 Participants n=209 Participants
Race (NIH/OMB) More than one race	0 Participants n=52 Participants	0 Participants n=27 Participants	0 Participants n=51 Participants	0 Participants n=27 Participants	0 Participants n=52 Participants	0 Participants n=209 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=52 Participants	5 Participants n=27 Participants	9 Participants n=51 Participants	5 Participants n=27 Participants	11 Participants n=52 Participants	38 Participants n=209 Participants
Region of Enrollment Germany	8 Participants n=52 Participants	5 Participants n=27 Participants	9 Participants n=51 Participants	4 Participants n=27 Participants	10 Participants n=52 Participants	36 Participants n=209 Participants
Region of Enrollment United States	44 Participants n=52 Participants	22 Participants n=27 Participants	42 Participants n=51 Participants	23 Participants n=27 Participants	42 Participants n=52 Participants	173 Participants n=209 Participants
Height	170.83 centimeters (cm) STANDARD_DEVIATION 10.991 • n=49 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	173.01 centimeters (cm) STANDARD_DEVIATION 9.273 • n=25 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	172.30 centimeters (cm) STANDARD_DEVIATION 9.335 • n=47 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	172.23 centimeters (cm) STANDARD_DEVIATION 10.972 • n=25 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	172.60 centimeters (cm) STANDARD_DEVIATION 9.603 • n=50 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	172.09 centimeters (cm) STANDARD_DEVIATION 9.972 • n=196 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.
Weight	87.25 kilograms (kg) STANDARD_DEVIATION 19.317 • n=49 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	82.92 kilograms (kg) STANDARD_DEVIATION 18.066 • n=25 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	87.26 kilograms (kg) STANDARD_DEVIATION 15.995 • n=47 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	82.84 kilograms (kg) STANDARD_DEVIATION 26.018 • n=25 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	85.64 kilograms (kg) STANDARD_DEVIATION 20.416 • n=50 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	85.73 kilograms (kg) STANDARD_DEVIATION 19.587 • n=196 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.
Body Mass Index (BMI)	29.84 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.920 • n=49 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	27.80 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 6.492 • n=25 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	29.45 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.465 • n=47 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	27.60 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 6.904 • n=25 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	28.76 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 6.652 • n=50 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.	28.93 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 6.206 • n=196 Participants • Number analyzed is the number of participants with data available for analysis at Baseline.

PRIMARY outcome

Timeframe: Day 1 (surgery) up to Day 10 postsurgery

Population: FAS included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 valid postbaseline on-treatment primary efficacy evaluation (bowel movement or tolerating solid food).

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=23 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=42 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=21 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=44 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Time From End of the Surgery to Resolution of Upper and Lower Gastrointestinal (GI) Function Postsurgery as Assessed by the Investigator	1.89 days Interval 1.41 to 5.79	2.76 days Interval 1.51 to 7.85	2.59 days Interval 0.85 to 4.97	2.62 days Interval 1.13 to 7.59	2.58 days Interval 1.46 to 7.74

SECONDARY outcome

Timeframe: Day 1 (surgery) up to Day 24

The time from the end of surgery (time the incision is closed) until ready for discharge was defined as time from end of surgery until the participant presented effective intestinal transit (spontaneous bowel movement), tolerated solids without vomiting or clinically significant nausea for 1 calendar day after a solid meal, had satisfactory pain control with oral analgesics, and was medically stable/free of complications. Kaplan-Meier survival analysis method was used.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=23 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=42 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=21 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=44 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Time From the End of the Surgery (Time the Incision is Closed) Until Ready for Discharge as Assessed by the Investigator	2.03 days Interval 1.41 to 16.83	2.82 days Interval 1.51 to 9.68	2.69 days Interval 0.85 to 8.79	2.94 days Interval 1.47 to 7.73	2.77 days Interval 1.51 to 7.74

SECONDARY outcome

Timeframe: Day 1 (surgery) up to Day 24

Kaplan-Meier survival analysis method was used.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=23 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=42 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=21 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=44 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Time From the End of Surgery Until the Discharge Order is Written	2.86 days Interval 1.62 to 16.72	3.95 days Interval 1.88 to 10.89	2.81 days Interval 0.89 to 11.09	2.94 days Interval 1.47 to 7.81	3.33 days Interval 1.56 to 14.74

SECONDARY outcome

Timeframe: Day 1 (surgery) up to Day 24

Kaplan-Meier survival analysis method was used.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=23 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=42 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=21 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=44 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Time From the End of Surgery to Discharge From Hospital	2.96 days Interval 1.72 to 16.76	4.06 days Interval 1.97 to 10.89	2.89 days Interval 1.0 to 11.11	3.05 days Interval 1.58 to 7.83	3.39 days Interval 1.7 to 14.77

SECONDARY outcome

Timeframe: Day 1 (surgery) up to Day 10 postsurgery

The time from end of surgery to tolerance of solid food was defined as intake of solids without vomiting or clinically significant nausea for 1 calendar day after a solid meal. Kaplan-Meier survival analysis method was used.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=23 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=42 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=21 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=44 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Time From End of Surgery to Tolerance of Solid Food as Assessed by the Investigator	1.82 days Interval 1.41 to 5.79	2.76 days Interval 1.51 to 7.85	2.36 days Interval 0.74 to 4.97	2.15 days Interval 1.13 to 7.59	2.55 days Interval 1.32 to 7.74

SECONDARY outcome

Timeframe: Day 1 (surgery) up to Day 10 postsurgery

The time from end of surgery to first spontaneous bowel movement was defined as a stool not induced by the use of enemas or laxatives. Kaplan-Meier survival analysis method was used.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=23 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=42 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=21 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=44 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Time From End of Surgery to First Spontaneous Bowel Movement as Assessed by the Investigator	1.56 days Interval 0.16 to 7.89	1.73 days Interval 0.11 to 3.81	1.11 days Interval 0.08 to 4.82	1.72 days Interval 0.2 to 3.23	1.74 days Interval 0.53 to 4.94

SECONDARY outcome

Timeframe: Day 1 (surgery) up to Day 10

Participants unable to tolerate solid foods, take anything by mouth, or requiring insertion or reinsertion of nasogastric (NG) tube at or after 5 days post-surgery. Percentages are rounded off to whole number at the nearest single decimal. Stratified Miettinen and Nurminen approach was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=23 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=42 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=21 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=44 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Percentage of Participants With Postoperative Gastrointestinal Dysfunction (POGD) >= 5 Days as Assessed by the Investigator	8.9 percentage of participants	8.7 percentage of participants	2.4 percentage of participants	4.8 percentage of participants	9.1 percentage of participants

SECONDARY outcome

Timeframe: Day 1 (surgery) up to Day 24 postsurgery (10 days of treatment period postsurgery plus 14-day observation period post last dose for recurrence of symptoms)

Participants who required insertion of NG tube postsurgery for drainage and symptom relief in case of persistent nausea and vomiting postsurgery were observed. Percentages are rounded off to whole number at the nearest single decimal. Stratified Miettinen and Nurminen approach was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=23 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=42 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=21 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=44 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Percentage of Participants Requiring Insertion of Nasogastric (NG) Tube Postsurgery	8.9 percentage of participants	0.0 percentage of participants	4.8 percentage of participants	4.8 percentage of participants	11.4 percentage of participants

SECONDARY outcome

Timeframe: Day 1 (surgery) up to first flatus (up to Day 10 postsurgery)

Kaplan-Meier survival analysis method was used.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=23 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=42 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=21 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=44 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Time From End of Surgery to First Flatus	1.21 days Interval 0.06 to 6.22	1.26 days Interval 0.28 to 7.62	0.96 days Interval 0.08 to 3.04	1.18 days Interval 0.2 to 2.82	1.12 days Interval 0.02 to 3.88

SECONDARY outcome

Timeframe: Day 1 (surgery): postinfusion

Population: PK Analysis Set included all participants who were randomized, received at least 1 dose and had at least 1 measurable post-dose plasma for TAK-954. Overall number analyzed is the number of participants with data available for analyses.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants TAK-954 placebo-matching, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=33 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=20 Participants TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=35 Participants TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Observed Plasma Concentration of TAK-954 at the End of Infusion on Day 1	1190 picograms per milliliter (pg/mL) Standard Deviation 480	5220 picograms per milliliter (pg/mL) Standard Deviation 1810	2500 picograms per milliliter (pg/mL) Standard Deviation 4140	12000 picograms per milliliter (pg/mL) Standard Deviation 28500	—

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 46 other events

Deaths: 0 deaths

TAK-954 0.1 mg/100 mL

Serious events: 9 serious events

Other events: 23 other events

Deaths: 0 deaths

TAK-954 0.5 mg/100 mL

Serious events: 8 serious events

Other events: 39 other events

Deaths: 0 deaths

TAK-954 0.1 mg/100 mL + Placebo

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

TAK-954 0.5 mg/100 mL + Placebo

Serious events: 11 serious events

Other events: 41 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=49 participants at risk TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once presurgery on Day 1 and once daily postsurgery until return of upper and lower gastrointestinal (GI) function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=26 participants at risk TAK-954 0.1 milligrams per 100 milliliters (mg/100 mL), 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=48 participants at risk TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=25 participants at risk TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=50 participants at risk TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Infections and infestations Abdominal abscess	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Abdominal pain	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Renal and urinary disorders Acute kidney injury	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Anastomotic leak	4.1% 2/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Cardiac disorders Cardiac arrest	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Colitis	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Crohn's disease	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
General disorders Dehiscence	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Diarrhoea	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Duodenitis	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Haematochezia	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Ileus	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Intra-abdominal fluid collection	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Intra-abdominal haemorrhage	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Mechanical ileus	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Infections and infestations Pneumonia	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Postoperative delirium	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Postoperative ileus	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.2% 2/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	10.0% 5/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Infections and infestations Postoperative wound infection	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Renal and urinary disorders Prerenal failure	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Renal and urinary disorders Urinoma	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Wound evisceration	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.

Other adverse events

Other adverse events
Measure	Placebo n=49 participants at risk TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once presurgery on Day 1 and once daily postsurgery until return of upper and lower gastrointestinal (GI) function or for up to 10 days.	TAK-954 0.1 mg/100 mL n=26 participants at risk TAK-954 0.1 milligrams per 100 milliliters (mg/100 mL), 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.5 mg/100 mL n=48 participants at risk TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.	TAK-954 0.1 mg/100 mL + Placebo n=25 participants at risk TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.	TAK-954 0.5 mg/100 mL + Placebo n=50 participants at risk TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
Gastrointestinal disorders Abdominal distension	10.2% 5/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	10.4% 5/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	10.0% 5/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Abdominal pain	4.1% 2/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.2% 2/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 2/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Blood and lymphatic system disorders Anaemia	14.3% 7/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	12.5% 6/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 2/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 4/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Anaemia postoperative	12.2% 6/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	18.8% 9/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 2/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	10.0% 5/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Cardiac disorders Bradycardia	6.1% 3/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	6.2% 3/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 2/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Constipation	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	7.7% 2/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Diarrhoea	14.3% 7/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	11.5% 3/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	22.9% 11/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 2/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	14.0% 7/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Dyspepsia	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	15.4% 4/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.2% 2/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Investigations Electrocardiogram QT prolonged	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 4/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Gastrooesophageal reflux disease	4.1% 2/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	12.0% 3/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 2/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Metabolism and nutrition disorders Hyperglycaemia	8.2% 4/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	6.2% 3/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	6.0% 3/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Vascular disorders Hypertension	12.2% 6/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	14.6% 7/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	14.0% 7/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Metabolism and nutrition disorders Hypocalcaemia	20.4% 10/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	20.8% 10/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	14.0% 7/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Metabolism and nutrition disorders Hypokalaemia	12.2% 6/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	19.2% 5/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.2% 2/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	16.0% 4/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	10.0% 5/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Metabolism and nutrition disorders Hypomagnesaemia	4.1% 2/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	15.4% 4/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	6.2% 3/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	14.0% 7/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Metabolism and nutrition disorders Hypophosphataemia	6.1% 3/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	19.2% 5/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	6.2% 3/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 4/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Vascular disorders Hypotension	6.1% 3/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.3% 4/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 4/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Blood and lymphatic system disorders Leukocytosis	12.2% 6/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.3% 4/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 4/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Nausea	44.9% 22/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	53.8% 14/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	41.7% 20/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	48.0% 12/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	38.0% 19/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.1% 2/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	6.0% 3/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Postoperative ileus	6.1% 3/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Procedural complication	6.1% 3/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Procedural hypertension	10.2% 5/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.3% 4/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Procedural hypotension	30.6% 15/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	18.8% 9/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	20.0% 10/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Procedural nausea	6.1% 3/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.1% 1/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 2/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Procedural pain	8.2% 4/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	19.2% 5/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.2% 2/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	16.0% 4/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 4/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
General disorders Pyrexia	6.1% 3/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	11.5% 3/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.2% 2/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Cardiac disorders Tachycardia	10.2% 5/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	3.8% 1/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.2% 2/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	6.0% 3/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Renal and urinary disorders Urinary retention	8.2% 4/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	11.5% 3/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	8.0% 2/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	2.0% 1/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Infections and infestations Urinary tract infection	0.00% 0/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.0% 1/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	6.0% 3/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Investigations Urine output decreased	2.0% 1/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	4.2% 2/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	0.00% 0/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	6.0% 3/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Vomiting	28.6% 14/49 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	30.8% 8/26 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	16.7% 8/48 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	36.0% 9/25 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.	22.0% 11/50 • From first dose of study drug up to Day 100 All-cause Mortality: All participants enrolled in the study. Serious and Other Adverse Events: Safety Set included all participants who were randomized and received at least 1 dose of double-blind study medication.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER