Intra-abdominal Infections
Conditions
Keywords
Complicated Intra-abdominal Infections
Brief summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of adding 125 mg or 250 mg doses of relebactam (MK-7655) to imipenem/cilastatin in adults 18 years or older with Complicated Intra-Abdominal Infection (cIAI). The primary hypothesis is that the relebactam + imipenem/cilastatin treatment regimen is non-inferior to treatment with imipenem/cilastatin alone with respect to the percentage of participants with a favorable clinical response at completion of intravenous (IV) study therapy.
Interventions
Relebactam 250 mg IV every 6 hours for a minimum of 96 hours
Relebactam 125 mg IV every 6 hours for a minimum of 96 hours
A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.
DRUGMatching placebo to relebactam
Placebo-matching infusion of IV normal saline (0.9%) once every 6 hours.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinically suspected and/or bacteriologically documented cIAI requiring hospitalization and treatment with IV antibiotic therapy. * Enrolled intraoperatively or postoperatively on the basis of operative findings OR enrolled preoperatively on the basis of compelling preoperative clinical findings.
Exclusion criteria
* Infection which should be managed by Staged Abdominal Repair (STAR) or open abdomen technique. * Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 30. * Any amount of effective antibiotic therapy after obtaining the culture for admission to this study and prior to the administration of the first dose of IV study therapy. * An infection which has been treated with \>24 hours of systemic antibiotic therapy known to be effective against the presumed or documented etiologic pathogen(s) within the 72-hour period immediately prior to consideration for entry into the study. * History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to carbapenem antibiotics, any cephalosporins, penicillins, or other β-lactam agents. * History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to other β-lactamase inhibitors (e.g., tazobactam, sulbactam, clavulanic acid). * History of a seizure disorder (requiring ongoing treatment with anticonvulsive therapy or prior treatment with anti-convulsive therapy in the last 3 years). * Currently being treated with valproic acid or has used valproic acid in the 2 weeks prior to screening. * Rapidly progressive or terminal illness (unlikely to survive the approximately 6- to 8-week study period). * Pregnant or expecting to conceive, breastfeeding, or plans to breast feed within 1 month of completion of the study. * Participant in whom a response to IV study therapy within the timeframe of treatment specified in this protocol is considered unlikely. * Concurrent infection that would interfere with evaluation of response to the study antibiotics. * Need for concomitant systemic antimicrobial agents in addition to those designated in the various study treatment groups. * cIAI due to a confirmed fungal pathogen. * Currently receiving immunosuppressive therapy, including use of high-dose corticosteroids. * Prior recipient of a renal transplantation. * Estimated or actual creatinine clearance of \<50 mL/minute. * History of any other illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drug to the patient. * Laboratory abnormalities as specified in protocol. * Currently participating in, or has participated in any other clinical study involving the administration of investigational or experimental medication (not licensed by regulatory agencies) at the time of presentation or during the previous 30 days prior to screening or is anticipated to participate in such a clinical study during the course of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Up to 42 days following completion of all study therapy (up to Day 56) | 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. |
| Percentage of Participants With Any Drug-related AE | Up to 14 days following completion of all study therapy (up to Day 28) | 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. |
| Percentage of Participants With Any Drug-related SAE | Up to 42 days following completion of all study therapy (up to Day 56) | 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. |
| Percentage of Participants Who Discontinued IV Study Therapy Due to an AE | Up to 14 days post initiation of IV study therapy (up to 14 days) | 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. |
| Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE | Up to 14 days post initiation of IV study therapy (up to 14 days) | 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. |
| Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Up to 42 days following completion of all study therapy (up to Day 56) | 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. |
| Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group | Up to 42 days following completion of all study therapy (up to Day 56) | 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. |
| Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy | 4 to 14 days post initiation of intravenous (IV) study therapy (up to postrandomization Day 14) | 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. |
| 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) | Up to 14 days following completion of all study therapy (up to Day 28) | 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. |
| 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 | Up to 14 days following completion of all study therapy (up to Day 28) | 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. |
| Percentage of Participants With Any Adverse Event (AE) | Up to 14 days following completion of all study therapy (up to Day 28) | 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. |
| Percentage of Participants With Any Serious Adverse Event (SAE) | Up to 14 days following completion of all study therapy (up to Day 28) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Favorable Clinical Response at Early Follow-up | Up to 9 days following completion of all study therapy (up to Day 23) | 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. |
| Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy | Up to 14 days post initiation of IV study therapy (up to postrandomization day 14) | 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. |
| Percentage of Participants With a Favorable Microbiological Response at Early Follow-up | Up to 9 days following completion of all study therapy (up to Day 23) | 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. |
| Percentage of Participants With a Favorable Clinical Response at Late Follow-up | Up to 42 days following completion of all study therapy (up to Day 56) | 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. |
| Percentage of Participants With a Favorable Microbiological Response at Late Follow-up | Up to 42 days following completion of all study therapy (up to Day 56) | 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. |
| Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy in Participants Who Have Imipenem-resistant, Gram-negative cIAI Infections. | 4 to 14 days post initiation of IV study therapy (up to postrandomization day 14). | 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. |
Participant flow
Recruitment details
Adults 18 years or older with complicated intra-abdominal infection (cIAI) requiring treatment with intravenous (IV) antibiotic therapy were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 118 |
| 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 | 116 |
| 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 | 117 |
| Total | 351 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Insufficient supply of study drug | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 |
| Overall Study | Progressive disease | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin | Total |
|---|---|---|---|---|
| Age, Continuous | 48.3 Years STANDARD_DEVIATION 18.9 | 49.8 Years STANDARD_DEVIATION 17.4 | 49.1 Years STANDARD_DEVIATION 17.8 | 49.1 Years STANDARD_DEVIATION 18 |
| Sex: Female, Male Female | 44 Participants | 54 Participants | 51 Participants | 149 Participants |
| Sex: Female, Male Male | 74 Participants | 62 Participants | 66 Participants | 202 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 117 | 3 / 116 | 0 / 114 |
| other Total, other adverse events | 16 / 117 | 15 / 116 | 13 / 114 |
| serious Total, serious adverse events | 4 / 117 | 13 / 116 | 8 / 114 |
Outcome results
Primary
Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE | 0 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE | 0.9 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE | 2.6 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Difference95% CI: [-7.5, 0.6]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference95% CI: [-6.7, 2.4]
Primary
Percentage of Participants Who Discontinued IV Study Therapy Due to an AE
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants Who Discontinued IV Study Therapy Due to an AE | 0.9 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants Who Discontinued IV Study Therapy Due to an AE | 4.3 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants Who Discontinued IV Study Therapy Due to an AE | 2.6 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Difference95% CI: [-6.7, 2.3]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference95% CI: [-3.7, 7.4]
Primary
Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy | 96.3 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy | 98.8 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy | 95.2 Percentage of participants |
Comparison: MK-7655 250 mg - Placebo: Percentage Differencep-value: <0.00195% CI: [-6.2, 8.6]Miettinen and Nurminen
Comparison: Relebactam 125 mg - Placebo: Percentage Differencep-value: <0.00195% CI: [-2, 10.8]Miettinen and Nurminen
Primary
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)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 125 mg With Imipenem/Cilastatin | 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) | 0 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | 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) | 1.8 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Differencep-value: 0.97995% CI: [-4.7, 4.5]Miettinen and Nurminen
Comparison: Relebactam 125 mg - Placebo: Percentage Differencep-value: 0.15395% CI: [-6.2, 1.5]Miettinen and Nurminen
Primary
Percentage of Participants With Any Adverse Event (AE)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Any Adverse Event (AE) | 48.7 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Any Adverse Event (AE) | 47.4 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Any Adverse Event (AE) | 41.2 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Difference95% CI: [-5.4, 20.1]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference95% CI: [-6.7, 18.8]
Primary
Percentage of Participants With Any Drug-related AE
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Any Drug-related AE | 13.7 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Any Drug-related AE | 13.8 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Any Drug-related AE | 9.6 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Difference95% CI: [-4.5, 12.7]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference95% CI: [-4.4, 12.8]
Primary
Percentage of Participants With Any Drug-related SAE
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Any Drug-related SAE | 0.9 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Any Drug-related SAE | 0 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Any Drug-related SAE | 0.9 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Difference95% CI: [-4, 3.9]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference95% CI: [-4.8, 2.4]
Primary
Percentage of Participants With Any Serious Adverse Event (SAE)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Any Serious Adverse Event (SAE) | 3.4 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Any Serious Adverse Event (SAE) | 9.5 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Any Serious Adverse Event (SAE) | 7 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Difference95% CI: [-10.3, 2.4]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference95% CI: [-5, 10.1]
Primary
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
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 125 mg With Imipenem/Cilastatin | 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 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | 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 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Differencep-value: 0.32495% CI: [-2.4, 4.7]Miettinen and Nurminen
Comparison: Relebactam 125 mg - Placebo: Percentage Differencep-value: >0.99995% CI: [-3.3, 3.2]Miettinen and Nurminen
Primary
Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group
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.
Time frame: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 125 mg With Imipenem/Cilastatin | 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 | 2.6 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | 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 | 2.6 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | 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 | 14.0 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group | ALT >5.0 X Baseline | 6.1 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | 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 | 5.5 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group | ALT >5.0 X Baseline | 3.6 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | 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 | 9.2 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | 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 | 9.1 Percentage of participants |
Primary
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
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.
Time frame: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | AST increased | 4.3 Percentage of participants |
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Post-operative wound infection | 2.6 Percentage of participants |
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Nausea | 6.8 Percentage of participants |
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | ALT increased | 4.3 Percentage of participants |
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Seroma | 0.9 Percentage of participants |
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Diarrhoea | 6.0 Percentage of participants |
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Lipase increased | 2.6 Percentage of participants |
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Vomiting | 6.0 Percentage of participants |
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Hypertension | 0 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | ALT increased | 4.3 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Diarrhoea | 6.0 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Nausea | 7.8 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Vomiting | 7.8 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Post-operative wound infection | 1.7 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Seroma | 4.3 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | AST increased | 4.3 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Lipase increased | 1.7 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Hypertension | 2.6 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Vomiting | 2.6 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Diarrhoea | 4.4 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | AST increased | 2.6 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Nausea | 7.0 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Hypertension | 3.5 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Lipase increased | 3.5 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Seroma | 0 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | Post-operative wound infection | 4.4 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group | ALT increased | 3.5 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Diarrhoea95% CI: [-4.7, 8.1]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Diarrhoea95% CI: [-4.6, 8.2]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Nausea95% CI: [-7.3, 6.9]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Nausea95% CI: [-6.5, 8]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Vomiting95% CI: [-2.3, 9.6]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Vomiting95% CI: [-0.7, 11.8]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Postoperative Infection95% CI: [-7.6, 3.5]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Postoperative Infection95% CI: [-8.4, 2.2]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Seroma95% CI: [-2.4, 4.7]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Seroma95% CI: [1, 9.7]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - ALT increased95% CI: [-5, 6.6]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - ALT increased95% CI: [-4.9, 6.7]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - AST increased95% CI: [-3.7, 7.3]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - AST increased95% CI: [-3.7, 7.4]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Lipase increased95% CI: [-6.5, 4.2]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Lipase increased95% CI: [-7.2, 3]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Hypertension95% CI: [-8.7, -0.3]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Hypertension95% CI: [-6.4, 4.3]
Primary
Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group
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.
Time frame: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | General disorders admin. site conditions | 5.2 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Blood and lymphatic system disorders | 0.9 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Cardiac disorders | 3.4 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Gastrointestinal disorders | 17.2 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Infections and infestations | 7.8 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Injury, poisoning, procedural complications | 6.9 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Investigations | 10.3 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Nervous system disorders | 3.4 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | 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 |
| Relebactam 125 mg With Imipenem/Cilastatin | 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 |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Respiratory, thoracic, mediastinal disorders | 4.3 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Skin, subcutaneous tissue disorders | 1.7 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Vascular disorders | 6.0 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Psychiatric disorders | 3.5 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Gastrointestinal disorders | 13.2 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Skin, subcutaneous tissue disorders | 1.8 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Renal and urinary disorders | 3.5 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | 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 |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | General disorders admin. site conditions | 3.5 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Respiratory, thoracic, mediastinal disorders | 6.1 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Investigations | 12.3 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Injury, poisoning, procedural complications | 5.3 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Blood and lymphatic system disorders | 5.3 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Nervous system disorders | 4.4 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Infections and infestations | 7.0 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group | Vascular disorders | 6.1 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Blood, lymphatic95% CI: [-7.3, 5.1]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Blood, lymphatic95% CI: [-10.3, 0.1]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Cardiac disorder95% CI: [-5.2, 5]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Cardiac disorder95% CI: [-4.5, 6.3]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - GI disorders95% CI: [-3.9, 15.3]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - GI disorders95% CI: [-5.4, 13.6]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Gen. dis \& admin.95% CI: [-2, 11]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Gen. dis \& admin.95% CI: [-4.2, 7.8]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Infect. \& Infest.95% CI: [-3.6, 12]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Infect. \& Infest.95% CI: [-6.5, 8]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Injury, poison.95% CI: [-7.3, 5.1]
Comparison: Relebactam 1250mg - Placebo: Percentage Difference - Injury, poison.95% CI: [-5, 8.5]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Investigations95% CI: [-9.8, 7.4]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Investigations95% CI: [-10.5, 6.5]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Nervous System95% CI: [-8.4, 2.2]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Nervous System95% CI: [-8.4, 2.2]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Psychiatric disorders95% CI: [-5.7, 5.4]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Psychiatric disorders95% CI: [-5.7, 5.5]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Renal \& Urinary95% CI: [-7.2, 3]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Renal \& Urinary95% CI: [-7.2, 3]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Resp. \& chest95% CI: [-10.7, 0.7]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Resp. \& chest95% CI: [-8.4, 4.4]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Skin \& subcutan.95% CI: [-2.4, 8.1]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Skin \& subcutan.95% CI: [-4.7, 4.5]
Comparison: Relebactam 250 mg - Placebo: Percentage Difference - Vascular disorders95% CI: [-9.9, 2]
Comparison: Relebactam 125 mg - Placebo: Percentage Difference - Vascular disorders95% CI: [-6.9, 6.6]
Secondary
Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy in Participants Who Have 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | 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 |
| Relebactam 125 mg With Imipenem/Cilastatin | 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 |
| Placebo to Relebactam With Imipenem/Cilastatin | 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 |
Comparison: Relebactam 250 mg - Placebo: Percentage Differencep-value: >0.99995% CI: [0, 0]Fisher Exact
Comparison: Relebactam 125 mg - Placebo: Percentage Differencep-value: >0.99995% CI: [0, 0]Fisher Exact
Secondary
Percentage of Participants With a Favorable Clinical Response at Early Follow-up
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Clinical Response at Early Follow-up | 94.9 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Clinical Response at Early Follow-up | 94.2 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With a Favorable Clinical Response at Early Follow-up | 96.3 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Differencep-value: 0.00195% CI: [-9.1, 6]Miettinen and Nurminen
Comparison: Relebactam 125 mg - Placebo: Percentage Differencep-value: 0.00295% CI: [-9.7, 5.3]Miettinen and Nurminen
Secondary
Percentage of Participants With a Favorable Clinical Response at Late Follow-up
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Clinical Response at Late Follow-up | 93.7 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Clinical Response at Late Follow-up | 95.3 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With a Favorable Clinical Response at Late Follow-up | 94.9 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Differencep-value: 0.00295% CI: [-9.6, 6.9]Miettinen and Nurminen
Comparison: Relebactam 125 mg - Placebo: Percentage Differencep-value: <0.00195% CI: [-7.2, 8.2]Miettinen and Nurminen
Secondary
Percentage of Participants With a Favorable Microbiological Response at Completion 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy | 97.6 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy | 100 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy | 97.6 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Differencep-value: <0.00195% CI: [-6.3, 6.2]Miettinen and Nurminen
Comparison: Relebactam 125 mg - Placebo: Percentage Differencep-value: <0.00195% CI: [-2, 8.3]Miettinen and Nurminen
Secondary
Percentage of Participants With a Favorable Microbiological Response at Early Follow-up
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Microbiological Response at Early Follow-up | 97.4 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Microbiological Response at Early Follow-up | 97.6 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With a Favorable Microbiological Response at Early Follow-up | 97.5 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Differencep-value: <0.00195% CI: [-6.7, 6.4]Miettinen and Nurminen
Comparison: Relebactam 125 mg - Placebo: Percentage Differencep-value: <0.00195% CI: [-6.3, 6.5]Miettinen and Nurminen
Secondary
Percentage of Participants With a Favorable Microbiological Response at Late Follow-up
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Microbiological Response at Late Follow-up | 96.2 Percentage of participants |
| Relebactam 125 mg With Imipenem/Cilastatin | Percentage of Participants With a Favorable Microbiological Response at Late Follow-up | 97.5 Percentage of participants |
| Placebo to Relebactam With Imipenem/Cilastatin | Percentage of Participants With a Favorable Microbiological Response at Late Follow-up | 96.2 Percentage of participants |
Comparison: Relebactam 250 mg - Placebo: Percentage Differencep-value: <0.00195% CI: [-7.4, 7.4]Miettinen and Nurminen
Comparison: Relebactam 125 mg - Placebo: Percentage Differencep-value: <0.00195% CI: [-5.2, 8.6]Miettinen and Nurminen