Trial Outcomes & Findings for Study of the Safety, Tolerability, and Efficacy of Relebactam (MK-7655) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone to Treat Complicated Intra-Abdominal Infection [cIAI] (MK-7655-004) (NCT NCT01506271)

NCT ID: NCT01506271

Last Updated: 2019-06-10

Results Overview

A favorable clinical response was assessed by the clinical investigator as a cure, and was defined as a situation where all or most pre-therapy signs and symptoms of the index infection had resolved, or returned to pre-infection status, and no additional antibiotic therapy was required.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 351 participants
• Primary outcome timeframe: 4 to 14 days post initiation of intravenous (IV) study therapy (up to postrandomization Day 14)
• Results posted on: 2019-06-10

Participant Flow

Adults 18 years or older with complicated intra-abdominal infection (cIAI) requiring treatment with intravenous (IV) antibiotic therapy were enrolled in this study.

Participant milestones

Measure	Relebactam 250 mg With Imipenem/Cilastatin Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Overall Study STARTED	118	116	117
Overall Study Treated	117	116	114
Overall Study COMPLETED	114	109	114
Overall Study NOT COMPLETED	4	7	3

Reasons for withdrawal

Measure	Relebactam 250 mg With Imipenem/Cilastatin Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Overall Study Progressive disease	0	1	0
Overall Study Protocol Violation	3	1	0
Overall Study Death	0	1	0
Overall Study Adverse Event	0	2	0
Overall Study Insufficient supply of study drug	1	0	0
Overall Study Withdrawal by Subject	0	1	1
Overall Study Lost to Follow-up	0	1	2

Baseline Characteristics

Study of the Safety, Tolerability, and Efficacy of Relebactam (MK-7655) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone to Treat Complicated Intra-Abdominal Infection [cIAI] (MK-7655-004)

Baseline characteristics by cohort

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=118 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=117 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Total n=351 Participants Total of all reporting groups
Age, Continuous	48.3 Years STANDARD_DEVIATION 18.9 • n=5 Participants	49.8 Years STANDARD_DEVIATION 17.4 • n=7 Participants	49.1 Years STANDARD_DEVIATION 17.8 • n=5 Participants	49.1 Years STANDARD_DEVIATION 18.0 • n=4 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	54 Participants n=7 Participants	51 Participants n=5 Participants	149 Participants n=4 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	62 Participants n=7 Participants	66 Participants n=5 Participants	202 Participants n=4 Participants

PRIMARY outcome

Timeframe: 4 to 14 days post initiation of intravenous (IV) study therapy (up to postrandomization Day 14)

Population: Those who had cIAI; a culture from the infection that grew one Gram negative pathogen; no protocol deviations; received ≥ 96 hours of IV therapy. Two participants treated with relebactam 250 mg, one with relebactam 125 mg, and two with placebo, all with indeterminate or missing responses, were excluded from the analysis.

A favorable clinical response was assessed by the clinical investigator as a cure, and was defined as a situation where all or most pre-therapy signs and symptoms of the index infection had resolved, or returned to pre-infection status, and no additional antibiotic therapy was required.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=81 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=86 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=83 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy	96.3 Percentage of participants Interval 89.6 to 99.2	98.8 Percentage of participants Interval 93.7 to 100.0	95.2 Percentage of participants Interval 88.1 to 98.7

PRIMARY outcome

Timeframe: Up to 14 days following completion of all study therapy (up to Day 28)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

Pre-specified events of interest were confirmed (i.e., verified by repeat testing) elevated AST or ALT laboratory value that is greater than or equal to 5 X ULN as a result of within-protocol-specific testing or unscheduled testing.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With an Elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Laboratory Values That Are Greater Than or Equal to 5X the Upper Limit of Normal (ULN)	1.7 Percentage of participants	0 Percentage of participants	1.8 Percentage of participants

PRIMARY outcome

Timeframe: Up to 14 days following completion of all study therapy (up to Day 28)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

Pre-specified events of interest were a confirmed (i.e., verified by repeat testing) elevated AST or ALT laboratory value that is greater than or equal to 3X ULN, as well as elevated total bilirubin greater than or equal to 2X the ULN, and alkaline phosphatase values that are less than 2X the ULN, as a result of within-protocol-specific testing or unscheduled testing.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With Elevated AST or ALT Laboratory Values >= 3X the ULN, Total Bilirubin >= 2X the ULN, and Alkaline Phosphatase Values < 2X the ULN	0.9 Percentage of participants	0 Percentage of participants	0 Percentage of participants

PRIMARY outcome

Timeframe: Up to 14 days following completion of all study therapy (up to Day 28)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With Any Adverse Event (AE)	48.7 Percentage of participants	47.4 Percentage of participants	41.2 Percentage of participants

PRIMARY outcome

Timeframe: Up to 14 days following completion of all study therapy (up to Day 28)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

A serious adverse event (SAE) is any AE occurring at any dose that is life threatening; results in a persistent or significant disability/incapacity; prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; or results in death.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With Any Serious Adverse Event (SAE)	3.4 Percentage of participants	9.5 Percentage of participants	7 Percentage of participants

PRIMARY outcome

Timeframe: Up to 14 days following completion of all study therapy (up to Day 28)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE. A drug-related AE is a AE determined by the investigator to be possibly, probably or definitely related to drug treatment.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With Any Drug-related AE	13.7 Percentage of participants	13.8 Percentage of participants	9.6 Percentage of participants

PRIMARY outcome

Timeframe: Up to 42 days following completion of all study therapy (up to Day 56)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

A SAE is any AE occurring at any dose that is life threatening; results in a persistent or significant disability/incapacity; prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; or results in death. A drug-related SAE is a SAE determined by the investigator to be possibly, probably or definitely related to drug treatment.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With Any Drug-related SAE	0.9 Percentage of participants	0 Percentage of participants	0.9 Percentage of participants

PRIMARY outcome

Timeframe: Up to 14 days post initiation of IV study therapy (up to 14 days)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE. AEs assessed by the investigator that caused discontinuation of participant treatment are presented.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants Who Discontinued IV Study Therapy Due to an AE	0.9 Percentage of participants	4.3 Percentage of participants	2.6 Percentage of participants

PRIMARY outcome

Timeframe: Up to 14 days post initiation of IV study therapy (up to 14 days)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE. A drug-related AE is an AE determined by the investigator to be possibly, probably or definitely related to drug treatment. Drug-related AEs assessed by the investigator that caused discontinuation of participant treatment are presented.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE	0 Percentage of participants	0.9 Percentage of participants	2.6 Percentage of participants

PRIMARY outcome

Timeframe: Up to 42 days following completion of all study therapy (up to Day 56)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the medicinal product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the medicinal product, is also an AE. AE preferred terms, with incidence greater than or equal to 4 in one treatment group are presented. AEs preferred terms which did not achieve this threshold are not reported. AE preferred terms are based on MedDRA version 17.0.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group Diarrhoea	6.0 Percentage of participants	6.0 Percentage of participants	4.4 Percentage of participants
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group Vomiting	6.0 Percentage of participants	7.8 Percentage of participants	2.6 Percentage of participants
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group ALT increased	4.3 Percentage of participants	4.3 Percentage of participants	3.5 Percentage of participants
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group Nausea	6.8 Percentage of participants	7.8 Percentage of participants	7.0 Percentage of participants
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group Post-operative wound infection	2.6 Percentage of participants	1.7 Percentage of participants	4.4 Percentage of participants
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group Seroma	0.9 Percentage of participants	4.3 Percentage of participants	0 Percentage of participants
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group AST increased	4.3 Percentage of participants	4.3 Percentage of participants	2.6 Percentage of participants
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group Lipase increased	2.6 Percentage of participants	1.7 Percentage of participants	3.5 Percentage of participants
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group Hypertension	0 Percentage of participants	2.6 Percentage of participants	3.5 Percentage of participants

PRIMARY outcome

Timeframe: Up to 42 days following completion of all study therapy (up to Day 56)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

Predefined limit of change (PDLC) are presented based on values from the following laboratory tests on serum: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Bil), and alkaline phosphatase (AP). Results are presented for PDLC from tests with reported incidence greater than or equal to 4 participants in one treatment group. Laboratory tests which did not achieve the PDLC threshold are not reported.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group ALT >5.0 X Baseline	4.5 Percentage of participants	6.1 Percentage of participants	3.6 Percentage of participants
Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group AST >2.5-5.0 X Baseline	14.5 Percentage of participants	14.0 Percentage of participants	9.2 Percentage of participants
Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group ALT >2.5-5.0 X Baseline	3.6 Percentage of participants	2.6 Percentage of participants	9.1 Percentage of participants
Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group AP >2.5-5.0 X Baseline	6.3 Percentage of participants	2.6 Percentage of participants	5.5 Percentage of participants

PRIMARY outcome

Timeframe: Up to 42 days following completion of all study therapy (up to Day 56)

Population: All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received

A system organ class (SOC) is the highest level of terminology used to describe disorders of the human body, and distinguishes by either anatomical or physiological systems, disease origin or purpose. SOCs with AE incidence greater than or equal to 4 in one treatment group are presented. SOCs with AE incidence which did not achieve this threshold are not reported. SOCs are based on MedDRA version 17.0.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Gastrointestinal disorders	18.8 Percentage of participants	17.2 Percentage of participants	13.2 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group General disorders admin. site conditions	7.7 Percentage of participants	5.2 Percentage of participants	3.5 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Infections and infestations	11.1 Percentage of participants	7.8 Percentage of participants	7.0 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Blood and lymphatic system disorders	4.3 Percentage of participants	0.9 Percentage of participants	5.3 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Cardiac disorders	2.6 Percentage of participants	3.4 Percentage of participants	2.6 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Injury, poisoning, procedural complications	4.3 Percentage of participants	6.9 Percentage of participants	5.3 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Investigations	11.1 Percentage of participants	10.3 Percentage of participants	12.3 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Nervous system disorders	1.7 Percentage of participants	3.4 Percentage of participants	4.4 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Psychiatric disorders	3.4 Percentage of participants	3.4 Percentage of participants	3.5 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Renal and urinary disorders	1.7 Percentage of participants	1.7 Percentage of participants	3.5 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Respiratory, thoracic, mediastinal disorders	1.7 Percentage of participants	4.3 Percentage of participants	6.1 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Skin, subcutaneous tissue disorders	4.3 Percentage of participants	1.7 Percentage of participants	1.8 Percentage of participants
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group Vascular disorders	2.6 Percentage of participants	6.0 Percentage of participants	6.1 Percentage of participants

SECONDARY outcome

Timeframe: 4 to 14 days post initiation of IV study therapy (up to postrandomization day 14).

Population: Met the protocol definition of cIAI; had a culture from the site of infection, that grew Gram-negative pathogen; had no significant deviations from the protocol that could impact the efficacy assessment; received ≥ 96 hours of IV study therapy; and had imipenem-resistant, gram negative cIAI infections.

A favorable clinical response is assessed by the clinical investigator as a cure, and is defined as a situation where all or most pre-therapy signs and symptoms of the index infection have resolved, or returned to pre-infection status, and no additional antibiotic therapy is required.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=14 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=9 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=11 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy in Participants Who Have Imipenem-resistant, Gram-negative cIAI Infections.	100 Percentage of participants Interval 76.8 to 100.0	100 Percentage of participants Interval 66.4 to 100.0	100 Percentage of participants Interval 71.5 to 100.0

SECONDARY outcome

Timeframe: Up to 9 days following completion of all study therapy (up to Day 23)

Population: Met the protocol definition of cIAI; had a culture from the site of infection, that grew Gram-negative pathogen; had no significant deviations from the protocol that could impact the efficacy assessment; received ≥ 96 hours of IV study therapy.

A favorable clinical response is assessed by the clinical investigator as a cure, and is defined as a situation where all or most pre-therapy signs and symptoms of the index infection have resolved, or returned to pre-infection status, and no additional antibiotic therapy is required.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=79 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=86 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=81 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With a Favorable Clinical Response at Early Follow-up	94.9 Percentage of participants Interval 87.5 to 98.6	94.2 Percentage of participants Interval 87.0 to 98.1	96.3 Percentage of participants Interval 89.6 to 99.2

SECONDARY outcome

Timeframe: Up to 14 days post initiation of IV study therapy (up to postrandomization day 14)

Population: Met the protocol definition of cIAI; had a pre-study/post operative culture from the site of infection grew at least one Gram-negative enteric and/or anaerobic pathogen; had no significant deviations from the protocol that could impact the efficacy assessment; and received ≥ 96 hours of IV study therapy.

A favorable microbiological response is assessed by the clinical investigator, and is defined as the eradication or presumptive eradication of all bacterial pathogens identified at baseline.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=83 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=86 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=84 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy	97.6 Percentage of participants Interval 91.6 to 99.7	100 Percentage of participants Interval 95.8 to 100.0	97.6 Percentage of participants Interval 91.7 to 99.7

SECONDARY outcome

Timeframe: Up to 9 days following completion of all study therapy (up to Day 23)

Population: Met the protocol definition of cIAI; had a pre-study/post operative culture from the site of infection grew at least one Gram-negative enteric and/or anaerobic pathogen; had no significant deviations from the protocol that could impact the efficacy assessment; and received ≥ 96 hours of IV study therapy.

A favorable microbiological response is assessed by the clinical investigator, and is defined as the eradication or presumptive eradication of all bacterial pathogens identified at baseline.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=78 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=82 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=80 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With a Favorable Microbiological Response at Early Follow-up	97.4 Percentage of participants Interval 91.0 to 99.7	97.6 Percentage of participants Interval 91.5 to 99.7	97.5 Percentage of participants Interval 91.3 to 99.7

SECONDARY outcome

Timeframe: Up to 42 days following completion of all study therapy (up to Day 56)

Population: Met the protocol definition of cIAI; had a pre-study/post operative culture from the site of infection grew at least one Gram-negative enteric and/or anaerobic pathogen; had no significant deviations from the protocol that could impact the efficacy assessment; and received ≥ 96 hours of IV study therapy.

A favorable clinical response is assessed by the clinical investigator as a cure, and is defined as a situation where all or most pre-therapy signs and symptoms of the index infection have resolved, or returned to pre-infection status, and no additional antibiotic therapy is required.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=79 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=85 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=79 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With a Favorable Clinical Response at Late Follow-up	93.7 Percentage of participants Interval 85.8 to 97.9	95.3 Percentage of participants Interval 88.4 to 98.7	94.9 Percentage of participants Interval 87.5 to 98.6

SECONDARY outcome

Timeframe: Up to 42 days following completion of all study therapy (up to Day 56)

Population: Met the protocol definition of cIAI; had a pre-study/post operative culture from the site of infection grew at least one Gram-negative enteric and/or anaerobic pathogen; had no significant deviations from the protocol that could impact the efficacy assessment; and received ≥ 96 hours of IV study therapy.

A favorable microbiological response is assessed by the clinical investigator, and is defined as the eradication or presumptive eradication of all bacterial pathogens identified at baseline.

Outcome measures

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=78 Participants Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=81 Participants Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=78 Participants Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Percentage of Participants With a Favorable Microbiological Response at Late Follow-up	96.2 Percentage of participants Interval 89.2 to 99.2	97.5 Percentage of participants Interval 91.4 to 99.7	96.2 Percentage of participants Interval 89.2 to 99.2

Adverse Events

Relebactam 250 mg With Imipenem/Cilastatin

Serious events: 4 serious events

Other events: 16 other events

Deaths: 0 deaths

Relebactam 125 mg With Imipenem/Cilastatin

Serious events: 13 serious events

Other events: 15 other events

Deaths: 3 deaths

Placebo to Relebactam With Imipenem/Cilastatin

Serious events: 8 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 participants at risk Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 participants at risk Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 participants at risk Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Injury, poisoning and procedural complications Suture rupture	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.88% 1/114 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Cardiac disorders Cardiac failure chronic	0.85% 1/117 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Cardiac disorders Cardiac failure congestive	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Cardiac disorders Ventricular fibrillation	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Gastrointestinal disorders Diarrhoea	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Gastrointestinal disorders Ileus paralytic	0.85% 1/117 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Gastrointestinal disorders Intestinal infarction	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.88% 1/114 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Hepatobiliary disorders Cholelithiasis obstructive	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.88% 1/114 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Infections and infestations Abdominal abscess	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.88% 1/114 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Infections and infestations Clostridium difficile infection	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Infections and infestations Liver abscess	0.85% 1/117 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Infections and infestations Postoperative wound infection	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Infections and infestations Septic shock	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Injury, poisoning and procedural complications Post procedural bile leak	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.88% 1/114 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.88% 1/114 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Injury, poisoning and procedural complications Wound evisceration	0.85% 1/117 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign gastrointestinal neoplasm	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mucinous adenocarcinoma of appendix	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.88% 1/114 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Nervous system disorders Cerebrovascular accident	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Renal and urinary disorders Renal failure acute	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.88% 1/114 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/116 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	1.8% 2/114 • Number of events 2 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Gastrointestinal disorders Pancreatitis Acute	0.00% 0/117 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.86% 1/116 • Number of events 1 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	0.00% 0/114 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.

Other adverse events

Measure	Relebactam 250 mg With Imipenem/Cilastatin n=117 participants at risk Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Relebactam 125 mg With Imipenem/Cilastatin n=116 participants at risk Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours	Placebo to Relebactam With Imipenem/Cilastatin n=114 participants at risk Participants received matching placebo to relebactam (normal saline 0.9%) IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours
Gastrointestinal disorders Diarrhoea	6.0% 7/117 • Number of events 8 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	5.2% 6/116 • Number of events 6 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	4.4% 5/114 • Number of events 5 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Gastrointestinal disorders Nausea	6.8% 8/117 • Number of events 9 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	7.8% 9/116 • Number of events 9 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	7.0% 8/114 • Number of events 9 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.
Gastrointestinal disorders Vomiting	6.0% 7/117 • Number of events 7 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	7.8% 9/116 • Number of events 9 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.	2.6% 3/114 • Number of events 3 • During study therapy and the protocol-specified follow-up period following end of study therapy (up to 28 days for non-serious AEs and up to 56 days for serious AEs) Population analyzed is all randomized participants who received at least one dose of IV study therapy. Participants with All-Cause Mortality were determined by the investigator to include some participants discontinued due to an adverse event, and progressive disease.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
• Publication restrictions are in place

Restriction type: OTHER