Trial Outcomes & Findings for Study to Evaluate Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery (NCT NCT01297959)

Last Updated: 2021-02-10

Results Overview

Superficial SSI: purulent drainage (PD) from superficial incision (SI), organisms isolated from aseptically obtained culture fluid from SI, pain/tenderness, localized swelling, redness, or heat extending from principal incision (PI), or PI deliberately opened by surgeon for presumptive PI infection and was culture-positive, a negative wound culture but clinical evidence of infection on Clinical Infection Wound Scale (CIWS). Deep incisional SSI: PD from deep incision (DI) but not from organ/space component of the surgical site, fever (\>38°C), localized wound pain, or wound tenderness, or DI spontaneously dehisces and/or deliberately opened by surgeon, and microbiological culture of DI by aseptic collection or deep wound swab was positive, an abscess or other evidence of infection involving DI was found on direct examination, during reoperation, or by histopathological or radiological examination, negative deep wound culture but clinical evidence of deep wound infection on CIWS.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

503 participants

Primary outcome timeframe

Surgery (Day 0) up to 30 days post-surgery

Results posted on

2021-02-10

Participant Flow

Participant milestones

Participant milestones
Measure	E-101 Solution 300 GU/mL Participants received 8 milliliter (mL) of E-101 Solution at porcine myeloperoxidase (pMPO) concentration of 300 guaiacol units per milliliter (GU/mL) applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Overall Study STARTED	261	242
Overall Study COMPLETED	241	226
Overall Study NOT COMPLETED	20	16

Reasons for withdrawal

Reasons for withdrawal
Measure	E-101 Solution 300 GU/mL Participants received 8 milliliter (mL) of E-101 Solution at porcine myeloperoxidase (pMPO) concentration of 300 guaiacol units per milliliter (GU/mL) applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Overall Study Adverse Event	0	1
Overall Study Protocol Violation	2	1
Overall Study Withdrawal by Subject	5	4
Overall Study Physician Decision	0	1
Overall Study Unrelated medical illness / complication	0	2
Overall Study Other	13	7

Baseline Characteristics

Study to Evaluate Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	E-101 Solution 300 GU/mL n=248 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=234 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Total n=482 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 14.68 • n=5 Participants	59.7 years STANDARD_DEVIATION 14.36 • n=7 Participants	59.7 years STANDARD_DEVIATION 14.51 • n=5 Participants
Sex: Female, Male Female	107 Participants n=5 Participants	93 Participants n=7 Participants	200 Participants n=5 Participants
Sex: Female, Male Male	141 Participants n=5 Participants	141 Participants n=7 Participants	282 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black	28 Participants n=5 Participants	19 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	211 Participants n=5 Participants	208 Participants n=7 Participants	419 Participants n=5 Participants
Race/Ethnicity, Customized Race · Others	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	235 Participants n=5 Participants	225 Participants n=7 Participants	460 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Unknown	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Surgery (Day 0) up to 30 days post-surgery

Population: ITT Analysis Set included all randomized participants in their assigned treatment group except those were found between randomization and before surgery to either meet exclusion criteria or not meet inclusion criteria, who withdrew consent or were treated at site 03-03 (participants were excluded because of a systematic problem in incisional SSI surveillance due to a lack of blinded assessors). Cumulative Treatment Incisional SSI was reported which included Superficial SSI and Deep SSI.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=241 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=225 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants In Intent to Treat (ITT) Analysis Set With Superficial and Deep Incisional Surgical Site Infections (SSI) Involving Principal Incision Within 30 Days After Index-surgery as Determined by Blinded Assessors 30 Days Post-operatively	53 Participants	41 Participants

PRIMARY outcome

Timeframe: Surgery (Day 0) up to 30 days post-surgery

Population: PP Analysis Set included all participants from ITT Analysis Set without any major protocol violations. Cumulative Treatment Incisional SSI was reported which included Superficial SSI and Deep SSI.

Superficial SSI: PD from SI, organisms isolated from aseptically obtained culture fluid from SI, pain/tenderness, localized swelling, redness, or heat extending from PI, or PI deliberately opened by surgeon for presumptive PI infection and was culture-positive, a negative wound culture but clinical evidence of infection on CIWS. Deep incisional SSI: PD from DI but not from organ/space component of the surgical site, fever (\>38°C), localized wound pain, or wound tenderness, or DI spontaneously dehisces and/or deliberately opened by surgeon, and microbiological culture of DI by aseptic collection or deep wound swab was positive, an abscess or other evidence of infection involving DI was found on direct examination, during reoperation, or by histopathological or radiological examination, negative deep wound culture but clinical evidence of deep wound infection on CIWS.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=197 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=196 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants In Per-Protocol (PP) Analysis Set With Superficial and Deep Incisional SSI Involving Principal Incision Within 30 Days After the Index-surgery as Determined by Blinded Assessors 30 Days Post-operatively	41 Participants	34 Participants

SECONDARY outcome

Timeframe: Surgery (Day 0) up to 30 days post-surgery

Population: Participants in the ITT Analysis Set with available data were analyzed.

CIWS was used postoperatively to evaluate the primary incisional wound for clinical evidence of infection. Score ranged from 0 (normal) - 5 (worst). 0: normal post-operative wound appearance, 1: wound erythema with pain extending ≥ 2 cm away from the primary incision, 2: spontaneous wound dehiscence with erythema and/or pain extending \< 2 cm along primary incision, 3: spontaneous wound dehiscence with erythema and/or pain extending ≥ 2 cm along primary incision, 4: PD from the primary incision, 5: infection of primary incision involving deep incisional structures (muscle and/or fascia) manifested by one or more of the following: spontaneous partial or complete wound dehiscence with erythema and/or pain, spontaneous PD, a wound abscess (based on palpitation findings of the surgeon and/or needle aspiration of purulence into palpable fluctuance, and/or ultrasound examination above the fascia), clinical or histological evidence of fasciitis or myonecrosis.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=235 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=220 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Mean Clinical Infection Wound Scale Score (CIWS)	0.4 score on a scale Standard Deviation 1.09	0.4 score on a scale Standard Deviation 1.17

SECONDARY outcome

Timeframe: Surgery (Day 0) up to 30 days post-surgery

Population: Participants in the ITT Analysis Set were analyzed.

Number of participants with objectively determined SSI (defined as participants with PD, wound abscess, or positive microbial culture from one or more incisional samples) are reported.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=241 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=225 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With Objectively Determined Incisional Surgical Site Infections (SSI)	33 Participants	26 Participants

SECONDARY outcome

Timeframe: Surgery (Day 0) up to 14 days post-surgery

Population: Participants in the ITT Analysis Set were analyzed. Cumulative Treatment Incisional SSI was reported which included Superficial SSI and Deep SSI.

Superficial SSI: PD from SI, organisms isolated from aseptically obtained culture fluid from SI, pain/tenderness, localized swelling, redness, or heat extending from PI, or PI deliberately opened by surgeon for presumptive PI infection and was culture-positive, a negative wound culture but CIWS. Deep incisional SSI: PD from DI but not from organ/space component of the surgical site, fever (\>38°C), localized wound pain, or wound tenderness, or DI spontaneously dehisces and/or deliberately opened by a surgeon, and microbiological culture of DI by aseptic collection or deep wound swab was positive, an abscess or other evidence of infection involving DI was found on direct examination, during reoperation, or by histopathological or radiological examination, negative deep wound culture but clinical evidence of deep wound infection on CIWS.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=241 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=225 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With Superficial and Deep Incisional Surgical Site Infections (SSI) Involving the Principal Incision (PI) Within 30 Days After the Index-surgery as Determined by Blinded Assessors 14 Days Post-operatively	50 Participants	52 Participants

SECONDARY outcome

Timeframe: Day 0 up to Day 30

Population: Participants in the ITT Analysis Set with available data were analyzed.

The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The mobility score questionnaire asked the participants to rate if they had problems walking around on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline mobility scale score was presented.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=190 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=178 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Worst Post-Baseline Mobility Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire	1.5 score on a scale Standard Deviation 0.56	1.6 score on a scale Standard Deviation 0.62

SECONDARY outcome

Timeframe: Day 0 up to Day 30

Population: Participants in the ITT Analysis Set with available data were analyzed.

The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The self-care questionnaire asked the participants to rate if they had any problems with self-care on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline self-care scale score was presented.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=190 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=178 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Worst Post-Baseline Self-Care Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire	1.6 score on a scale Standard Deviation 0.68	1.6 score on a scale Standard Deviation 0.65

SECONDARY outcome

Timeframe: Day 0 up to Day 30

Population: Participants in the ITT Analysis Set with available data were analyzed.

The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The usual activity questionnaire asked the participants to rate if they had any problems with usual activities on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline usual activity scale score was presented.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=190 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=178 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Worst Post-Baseline Usual Activity Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire	2.1 score on a scale Standard Deviation 0.64	2.0 score on a scale Standard Deviation 0.67

SECONDARY outcome

Timeframe: Day 0 up to Day 30

Population: Participants in the ITT Analysis Set with available data were analyzed.

The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The pain/discomfort score questionnaire asked the participants to rate if they had any pain or discomfort on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline pain/discomfort scale score was presented.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=190 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=178 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Worst Post-Baseline Pain/Discomfort Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire	1.9 score on a scale Standard Deviation 0.53	1.9 score on a scale Standard Deviation 0.54

SECONDARY outcome

Timeframe: Day 0 up to Day 30

Population: Participants in the ITT Analysis Set with available data were analyzed.

The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The anxiety/depression questionnaire asked the participants to rate if they had any anxiety or depression on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline anxiety/depression scale score was presented.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=190 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=178 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Worst Post-Baseline Anxiety/Depression Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire	1.4 score on a scale Standard Deviation 0.55	1.4 score on a scale Standard Deviation 0.60

SECONDARY outcome

Timeframe: Day 0 up to Day 30

Population: Participants in the ITT Analysis Set with available data were analyzed.

The EQ-5D health state scale is a visual analog scale that ranges from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating a better state of health. Participants were asked to rate their health state from 0 to 100. The mean worst post-baseline health state score was reported.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=190 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=178 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Worst Post-Baseline Health State Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire	64.7 score on a scale Standard Deviation 20.77	61.3 score on a scale Standard Deviation 24.31

SECONDARY outcome

Timeframe: Surgery (Day 0) up to 30 days post-surgery

Population: Participants in the ITT Analysis Set were analyzed.

Number of participants who had re-hospitalization for SSI were reported.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=241 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=225 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With Re-Hospitalization	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Day 3 up to Day 30

Population: Participants in the Safety Analysis Set (all participants randomized to treatment and exposed to any quantity of study drug) with available data were analyzed.

CWHS was assessed by blind assessors as 0= normal, intact incision without any spontaneous wound dehiscence; 1= spontaneous wound dehiscence that extends \< 2 cm along the principal incision in the absence of erythema and/or pain 2= spontaneous wound dehiscence that extends ≥ 2 cm along the principal incision in the absence of erythema and/or pain. Number of participants with various levels of CWHS scores were reported.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=206 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=198 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With Clinical Wound Healing Score (CWHS) as Assessed by Blinded Assessors CWHS =0	193 Participants	185 Participants
Number of Participants With Clinical Wound Healing Score (CWHS) as Assessed by Blinded Assessors CWHS =1	10 Participants	12 Participants
Number of Participants With Clinical Wound Healing Score (CWHS) as Assessed by Blinded Assessors CWHS =2	3 Participants	1 Participants

SECONDARY outcome

Timeframe: From first dose up to 30 days post-surgery

Population: Participants in the Safety Analysis Set were analyzed.

AE: Any untoward medical occurrence in a participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. ADR: All noxious and unintended responses to a medicinal product related to any dose. SAE: AE that resulted in any of the following: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: an event that was not present prior to administration of study medication, or, if present prior to administration of study medication, increases in intensity after administration of study medication during study. SUSAR: all suspected adverse reactions (ARs) related to an investigational medicinal product (IMP) that occurred in study, and that were both unexpected and serious. UAR: an ARs, nature and severity of which was not consistent with the current medicinal product information.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=248 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=234 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (TEAEs), Adverse Drug Reactions (ADRs), Suspected Unexpected Serious Adverse Reactions (SUSARs) and Unexpected Adverse Reactions (UARs) AEs	218 Participants	202 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (TEAEs), Adverse Drug Reactions (ADRs), Suspected Unexpected Serious Adverse Reactions (SUSARs) and Unexpected Adverse Reactions (UARs) SAEs	57 Participants	56 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (TEAEs), Adverse Drug Reactions (ADRs), Suspected Unexpected Serious Adverse Reactions (SUSARs) and Unexpected Adverse Reactions (UARs) TEAEs	215 Participants	201 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (TEAEs), Adverse Drug Reactions (ADRs), Suspected Unexpected Serious Adverse Reactions (SUSARs) and Unexpected Adverse Reactions (UARs) ADRs	10 Participants	10 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (TEAEs), Adverse Drug Reactions (ADRs), Suspected Unexpected Serious Adverse Reactions (SUSARs) and Unexpected Adverse Reactions (UARs) SUSARs	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (TEAEs), Adverse Drug Reactions (ADRs), Suspected Unexpected Serious Adverse Reactions (SUSARs) and Unexpected Adverse Reactions (UARs) UARs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose up to 30 days post-surgery

Population: Participants in the Safety Analysis Set were analyzed.

Number of participants with clinically significant laboratory findings were reported. The clinical significance was decided by the investigator.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=248 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=234 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With Clinically Significant Laboratory Findings	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose up to 30 days post-surgery

Population: Participants in the Safety Analysis Set were analyzed.

Number of participants with clinically significant physical examination findings were reported. The clinical significance was decided by the investigator.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=248 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=234 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With Clinically Significant Physical Examination Findings	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Surgery (Day 0) up to 30 days post-surgery

Population: Participants in the Safety Analysis Set with available date were analyzed.

Number of participants with wound pain assessment scores were assessed on a categorical scale ranging from 0 to 10, where 0 is no pain and 10 is unimaginable, unspeakable pain. Higher number on the scale represents worst possible pain.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=207 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=200 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 0	8 Participants	9 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 1	7 Participants	10 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 2	15 Participants	20 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 3	25 Participants	25 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 4	37 Participants	26 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 5	26 Participants	31 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 6	29 Participants	26 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 7	24 Participants	23 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 8	23 Participants	18 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 9	3 Participants	8 Participants
Number of Participants by Wound Pain Assessment Scores Wound Pain Scale Score 10	10 Participants	4 Participants

SECONDARY outcome

Timeframe: Day 14 and Day 30

Population: Participants in the Antibody Safety Set (all participants who were randomized to and exposed to any quantity of study drug with sufficient data to determine antibody results) with available data were analyzed.

Antibody assessment was done using enzyme-linked immunosorbent assay (ELISA) test.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=229 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=201 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody pANCA IgG: Day 14	1 Participants	1 Participants
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody pANCA IgG: Day 30	1 Participants	1 Participants
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody Serum Anti-GO IgG,M,A: Day 14	14 Participants	1 Participants
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody Serum Anti-GO IgG,M,A: Day 30	25 Participants	8 Participants
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody Anti-pMPO IgG,M,A: Day 14	48 Participants	1 Participants
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody Anti-pMPO IgG,M,A: Day 30	175 Participants	1 Participants
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody Serum GO Neutralization: Day 14	3 Participants	0 Participants
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody Serum GO Neutralization: Day 30	6 Participants	0 Participants
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody Serum pMPO Neutralization: Day 14	1 Participants	0 Participants
Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody Serum pMPO Neutralization: Day 30	18 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 3 and Month 6

Population: Participants in the Antibody Safety Set with available data were analyzed.

Antibody assessment was done using ELISA test.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=71 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=2 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody pANCA IgG: Month 3	0 Participants	0 Participants
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody pANCA IgG: Month 6	0 Participants	—
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody Serum Anti-GO IgG,M,A: Month 3	3 Participants	1 Participants
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody Serum Anti-GO IgG,M,A: Month 6	1 Participants	—
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody Anti-pMPO IgG,M,A: Month 3	60 Participants	0 Participants
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody Anti-pMPO IgG,M,A: Month 6	31 Participants	—
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody Serum GO Neutralization: Month 3	0 Participants	0 Participants
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody Serum GO Neutralization: Month 6	0 Participants	—
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody Serum pMPO Neutralization: Month 3	14 Participants	—
Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody Serum pMPO Neutralization: Month 6	5 Participants	—

SECONDARY outcome

Timeframe: Day 30, Month 3 and Month 6

Population: Participants in the Safety Analysis Set were analyzed.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=248 Participants Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=234 Participants Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Number of Participants With Serum pANCA and pMPO Antibody Response pANCA: Month 3	0 Participants	0 Participants
Number of Participants With Serum pANCA and pMPO Antibody Response pANCA: Day 30	1 Participants	1 Participants
Number of Participants With Serum pANCA and pMPO Antibody Response pANCA: Month 6	0 Participants	0 Participants
Number of Participants With Serum pANCA and pMPO Antibody Response Serum pMPO: Day 30	18 Participants	0 Participants
Number of Participants With Serum pANCA and pMPO Antibody Response Serum pMPO: Month 3	14 Participants	0 Participants
Number of Participants With Serum pANCA and pMPO Antibody Response Serum pMPO: Month 6	5 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Surgery (Day 0) up to to 30 days post surgery

Population: Per Protocol Analysis Set; only participant samples with isolated pathogens were included in the analysis

In vitro activity of the study drug against a range of aerobic and anaerobic pathogenic isolates cultured from infected principal incisions was analyzed using MIC. MIC 90 is defined as the lowest concentration of study drug that inhibits the growth of 90% of aerobic microorganisms tested.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=76 isolates Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Minimum Inhibitory Concentration (MIC) at 90% Aerobic	0.25 mg pMPO/mL	—
Minimum Inhibitory Concentration (MIC) at 90% Anaerobic	NA mg pMPO/mL A lower threshold was not established (that is, the lowest possible administered doses inhibited anaerobic pathogens)	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Surgery (Day 0) up to to 30 days post surgery

Population: Per Protocol Analysis Set; only participant samples with isolated pathogens were included in the analysis

In vitro activity of the study drug against a range of aerobic and anaerobic pathogenic isolates cultured from infected principal incisions was analyzed using MBC. MBC 90 is defined as the lowest concentration of study drug required to kill greater than or equal to 99.9% (bactericidal) of the aerobic microorganisms tested.

Outcome measures

Outcome measures
Measure	E-101 Solution 300 GU/mL n=76 isolates Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Minimum Bactericidal Concentration (MBC) at 90% Aerobic	0.5 mg pMPO/mL	—
Minimum Bactericidal Concentration (MBC) at 90% Anaerobic	NA mg pMPO/mL A lower threshold was not established (that is, the lowest possible administered doses inhibited anaerobic pathogens)	—

Adverse Events

E-101 Solution 300 GU/mL

Serious events: 57 serious events

Other events: 180 other events

Deaths: 2 deaths

Placebo (Saline Solution)

Serious events: 56 serious events

Other events: 174 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Jackson T Stephens, Jr

Excited States/Exoxemis, Inc

Phone: (402) 884-2316

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	E-101 Solution 300 GU/mL n=248 participants at risk Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Placebo (Saline Solution) n=234 participants at risk Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Cardiac disorders Tachycardia	10.9% 27/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	12.4% 29/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Gastrointestinal disorders Abdominal distension	8.1% 20/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	12.0% 28/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Gastrointestinal disorders Constipation	6.9% 17/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	6.0% 14/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Gastrointestinal disorders Diarrhoea	5.6% 14/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	6.0% 14/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Gastrointestinal disorders Dyspepsia	6.0% 15/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	4.7% 11/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Gastrointestinal disorders Nausea	39.5% 98/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	39.7% 93/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Gastrointestinal disorders Vomiting	13.7% 34/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	17.1% 40/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
General disorders Pyrexia	15.3% 38/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	15.0% 35/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	5.2% 13/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	3.4% 8/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Investigations Blood magnesium decreased	4.4% 11/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	7.7% 18/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Investigations Blood phosphorus decreased	4.8% 12/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	8.1% 19/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Investigations Haemoglobin decreased	4.8% 12/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	8.1% 19/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Investigations Oxygen saturation decreased	5.2% 13/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	7.3% 17/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Investigations Urine output decreased	2.0% 5/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	7.3% 17/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Metabolism and nutrition disorders Hypokalaemia	12.5% 31/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	12.8% 30/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	8.9% 22/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	10.3% 24/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Metabolism and nutrition disorders Hypophosphataemia	7.7% 19/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	4.7% 11/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Psychiatric disorders Insomnia	6.9% 17/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	8.5% 20/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.8% 7/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	6.8% 16/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Skin and subcutaneous tissue disorders Pruritus	8.1% 20/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	6.8% 16/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Vascular disorders Hypotension	8.9% 22/248 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.	8.1% 19/234 • From first dose up to 30 days post-surgery Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.