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)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01506271
Collaborator
(none)
351
3
26.3
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
351 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase II, Randomized, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of MK-7655 + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone in Patients With Complicated Intra-Abdominal Infection [cIAI]
Actual Study Start Date
:
Jun 1, 2012
Actual Primary Completion Date
:
Aug 12, 2014
Actual Study Completion Date
:
Aug 12, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Relebactam 250 mg with imipenem/cilastatin Participants randomized to receive relebactam 250 mg will be administered 250 mg doses of relebactam IV in a blinded fashion once every 6 hours with each dose infused over a 30-minute interval. A 500 mg dose of imipenem/cilastatin will be administered in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval. |
Drug: Relebactam 250 mg
Relebactam 250 mg IV every 6 hours for a minimum of 96 hours
Other Names:
Drug: Imipenem/cilastatin
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.
|
| Experimental: Relebactam 125 mg with imipenem/cilastatin Participants randomized to receive relebactam 125 mg will be administered 125 mg doses of relebactam IV, in a blinded-treatment fashion once every 6 hours with each dose infused over a 30-minute interval. 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. |
Drug: Relebactam 125 mg
Relebactam 125 mg IV every 6 hours for a minimum of 96 hours
Other Names:
Drug: Imipenem/cilastatin
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.
|
| Placebo Comparator: Placebo to relebactam with imipenem/cilastatin Participants randomized to receive placebo for relebactam will receive a placebo-matching infusion of IV normal saline (0.9%) once every 6 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. |
Drug: Imipenem/cilastatin
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.
Drug: Matching placebo to relebactam
Placebo-matching infusion of IV normal saline (0.9%) once every 6 hours.
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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 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.
Secondary Outcome Measures
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01506271
Other Study ID Numbers:
- 7655-004
- 2011-005686-20
- MK-7655-004
First Posted:
Jan 9, 2012
Last Update Posted:
Jun 10, 2019
Last Verified:
Jun 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Merck Sharp & Dohme LLC
Additional relevant MeSH terms:
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Period Title: Overall Study | |||
| STARTED | 118 | 116 | 117 |
| Treated | 117 | 116 | 114 |
| COMPLETED | 114 | 109 | 114 |
| NOT COMPLETED | 4 | 7 | 3 |
Baseline Characteristics
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 of all reporting groups |
| Overall Participants | 118 | 116 | 117 | 351 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
48.3
(18.9)
|
49.8
(17.4)
|
49.1
(17.8)
|
49.1
(18.0)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
44
37.3%
|
54
46.6%
|
51
43.6%
|
149
42.5%
|
| Male |
74
62.7%
|
62
53.4%
|
66
56.4%
|
202
57.5%
|
Outcome Measures
| Title | Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 81 | 86 | 83 |
| Number (95% Confidence Interval) [Percentage of participants] |
96.3
81.6%
|
98.8
85.2%
|
95.2
81.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | MK-7655 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority test based on unconditional asymptotic Miettinen and Nurminen method without stratification. | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 1.1 | |
| Confidence Interval |
(2-Sided) 95% -6.2 to 8.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority test based on unconditional asymptotic Miettinen and Nurminen method without stratification. | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 3.7 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 10.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | 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) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Number [Percentage of participants] |
1.7
1.4%
|
0
0%
|
1.8
1.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Test for a non-zero difference. | |
| Statistical Test of Hypothesis | p-Value | 0.979 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% -4.7 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Test for a non-zero difference. | |
| Statistical Test of Hypothesis | p-Value | 0.153 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -6.2 to 1.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Number [Percentage of participants] |
0.9
0.8%
|
0
0%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Test for a non-zero difference. | |
| Statistical Test of Hypothesis | p-Value | 0.324 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0.9 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to 4.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Test for a non-zero difference | |
| Statistical Test of Hypothesis | p-Value | > 0.999 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% -3.3 to 3.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With Any Adverse Event (AE) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Number [Percentage of participants] |
48.7
41.3%
|
47.4
40.9%
|
41.2
35.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 7.5 | |
| Confidence Interval |
(2-Sided) 95% -5.4 to 20.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 6.2 | |
| Confidence Interval |
(2-Sided) 95% -6.7 to 18.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With Any Serious Adverse Event (SAE) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Number [Percentage of participants] |
3.4
2.9%
|
9.5
8.2%
|
7
6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -3.6 | |
| Confidence Interval |
(2-Sided) 95% -10.3 to 2.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 2.5 | |
| Confidence Interval |
(2-Sided) 95% -5.0 to 10.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With Any Drug-related AE |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Number [Percentage of participants] |
13.7
11.6%
|
13.8
11.9%
|
9.6
8.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 4.0 | |
| Confidence Interval |
(2-Sided) 95% -4.5 to 12.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 4.1 | |
| Confidence Interval |
(2-Sided) 95% -4.4 to 12.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With Any Drug-related SAE |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Number [Percentage of participants] |
0.9
0.8%
|
0
0%
|
0.9
0.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% -4.0 to 3.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -4.8 to 2.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants Who Discontinued IV Study Therapy Due to an AE |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Number [Percentage of participants] |
0.9
0.8%
|
4.3
3.7%
|
2.6
2.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -6.7 to 2.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 1.7 | |
| Confidence Interval |
(2-Sided) 95% -3.7 to 7.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Number [Percentage of participants] |
0
0%
|
0.9
0.8%
|
2.6
2.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -2.6 | |
| Confidence Interval |
(2-Sided) 95% -7.5 to 0.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -6.7 to 2.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Diarrhoea |
6.0
5.1%
|
6.0
5.2%
|
4.4
3.8%
|
| Nausea |
6.8
5.8%
|
7.8
6.7%
|
7.0
6%
|
| Vomiting |
6.0
5.1%
|
7.8
6.7%
|
2.6
2.2%
|
| Post-operative wound infection |
2.6
2.2%
|
1.7
1.5%
|
4.4
3.8%
|
| Seroma |
0.9
0.8%
|
4.3
3.7%
|
0
0%
|
| ALT increased |
4.3
3.6%
|
4.3
3.7%
|
3.5
3%
|
| AST increased |
4.3
3.6%
|
4.3
3.7%
|
2.6
2.2%
|
| Lipase increased |
2.6
2.2%
|
1.7
1.5%
|
3.5
3%
|
| Hypertension |
0
0%
|
2.6
2.2%
|
3.5
3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Diarrhoea | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 1.6 | |
| Confidence Interval |
(2-Sided) 95% -4.7 to 8.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Diarrhoea | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 1.6 | |
| Confidence Interval |
(2-Sided) 95% -4.6 to 8.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Nausea | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -7.3 to 6.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Nausea | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -6.5 to 8.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Vomiting | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 3.4 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to 9.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Vomiting | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 5.1 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 11.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Postoperative Infection | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -7.6 to 3.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Postoperative Infection | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -2.7 | |
| Confidence Interval |
(2-Sided) 95% -8.4 to 2.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Seroma | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0.9 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to 4.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Seroma | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 4.3 | |
| Confidence Interval |
(2-Sided) 95% 1.0 to 9.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - ALT increased | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0.8 | |
| Confidence Interval |
(2-Sided) 95% -5.0 to 6.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - ALT increased | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0.8 | |
| Confidence Interval |
(2-Sided) 95% -4.9 to 6.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - AST increased | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 1.6 | |
| Confidence Interval |
(2-Sided) 95% -3.7 to 7.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - AST increased | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 1.7 | |
| Confidence Interval |
(2-Sided) 95% -3.7 to 7.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Lipase increased | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -6.5 to 4.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Lipase increased | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -7.2 to 3.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Relebactam 125 mg With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Hypertension | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -3.5 | |
| Confidence Interval |
(2-Sided) 95% -8.7 to -0.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Hypertension | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -6.4 to 4.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy in Participants Who Have Imipenem-resistant, Gram-negative cIAI Infections. |
|---|---|
| Description | 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 14 | 9 | 11 |
| Number (95% Confidence Interval) [Percentage of participants] |
100
84.7%
|
100
86.2%
|
100
85.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | > 0.999 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% 0 to 0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | > 0.999 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% 0 to 0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With a Favorable Clinical Response at Early Follow-up |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 79 | 86 | 81 |
| Number (95% Confidence Interval) [Percentage of participants] |
94.9
80.4%
|
94.2
81.2%
|
96.3
82.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification. | |
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.4 | |
| Confidence Interval |
(2-Sided) 95% -9.1 to 6.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification. | |
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -2.1 | |
| Confidence Interval |
(2-Sided) 95% -9.7 to 5.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 83 | 86 | 84 |
| Number (95% Confidence Interval) [Percentage of participants] |
97.6
82.7%
|
100
86.2%
|
97.6
83.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Two participants with indeterminate or missing response were excluded from the analysis. | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% -6.3 to 6.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Two participants with indeterminate or missing response were excluded from the analysis. | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 2.4 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 8.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With a Favorable Microbiological Response at Early Follow-up |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 78 | 82 | 80 |
| Number (95% Confidence Interval) [Percentage of participants] |
97.4
82.5%
|
97.6
84.1%
|
97.5
83.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Eight participants with indeterminate or missing response were excluded from the analysis. | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -6.7 to 6.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Eight participants with indeterminate or missing response were excluded from the analysis. | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -6.3 to 6.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With a Favorable Clinical Response at Late Follow-up |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 79 | 85 | 79 |
| Number (95% Confidence Interval) [Percentage of participants] |
93.7
79.4%
|
95.3
82.2%
|
94.9
81.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority test based on Unconditional asymptotic Miettinen and Nurminen method without stratification. | |
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.3 | |
| Confidence Interval |
(2-Sided) 95% -9.6 to 6.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification. | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -7.2 to 8.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With a Favorable Microbiological Response at Late Follow-up |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 78 | 81 | 78 |
| Number (95% Confidence Interval) [Percentage of participants] |
96.2
81.5%
|
97.5
84.1%
|
96.2
82.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Eight participants with indeterminate or missing response were excluded from the analysis. | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% -7.4 to 7.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Eight participants with indeterminate or missing response were excluded from the analysis. | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% -5.2 to 8.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
| Title | Percentage of Participants With Predefined Limit of Change (PDLC) With Incidence of >= 4 Participants in One Treatment Group |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| ALT >2.5-5.0 X Baseline |
3.6
3.1%
|
2.6
2.2%
|
9.1
7.8%
|
| ALT >5.0 X Baseline |
4.5
3.8%
|
6.1
5.3%
|
3.6
3.1%
|
| AST >2.5-5.0 X Baseline |
14.5
12.3%
|
14.0
12.1%
|
9.2
7.9%
|
| AP >2.5-5.0 X Baseline |
6.3
5.3%
|
2.6
2.2%
|
5.5
4.7%
|
| Title | Percentage of Participants With System Organ Class (SOC) With AEs With Incidence of >= 4 Participants in One Treatment Group |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of IV study therapy, based on the therapy they actually received |
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|---|
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 |
| Measure Participants | 117 | 116 | 114 |
| Blood and lymphatic system disorders |
4.3
3.6%
|
0.9
0.8%
|
5.3
4.5%
|
| Cardiac disorders |
2.6
2.2%
|
3.4
2.9%
|
2.6
2.2%
|
| Gastrointestinal disorders |
18.8
15.9%
|
17.2
14.8%
|
13.2
11.3%
|
| General disorders admin. site conditions |
7.7
6.5%
|
5.2
4.5%
|
3.5
3%
|
| Infections and infestations |
11.1
9.4%
|
7.8
6.7%
|
7.0
6%
|
| Injury, poisoning, procedural complications |
4.3
3.6%
|
6.9
5.9%
|
5.3
4.5%
|
| Investigations |
11.1
9.4%
|
10.3
8.9%
|
12.3
10.5%
|
| Nervous system disorders |
1.7
1.4%
|
3.4
2.9%
|
4.4
3.8%
|
| Psychiatric disorders |
3.4
2.9%
|
3.4
2.9%
|
3.5
3%
|
| Renal and urinary disorders |
1.7
1.4%
|
1.7
1.5%
|
3.5
3%
|
| Respiratory, thoracic, mediastinal disorders |
1.7
1.4%
|
4.3
3.7%
|
6.1
5.2%
|
| Skin, subcutaneous tissue disorders |
4.3
3.6%
|
1.7
1.5%
|
1.8
1.5%
|
| Vascular disorders |
2.6
2.2%
|
6.0
5.2%
|
6.1
5.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Blood, lymphatic | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -7.3 to 5.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Blood, lymphatic | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -4.4 | |
| Confidence Interval |
(2-Sided) 95% -10.3 to 0.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Cardiac disorder | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -5.2 to 5.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Cardiac disorder | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0.8 | |
| Confidence Interval |
(2-Sided) 95% -4.5 to 6.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - GI disorders | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 5.6 | |
| Confidence Interval |
(2-Sided) 95% -3.9 to 15.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - GI disorders | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 4.1 | |
| Confidence Interval |
(2-Sided) 95% -5.4 to 13.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Gen. dis & admin. | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 4.2 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 11.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Gen. dis & admin. | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 1.7 | |
| Confidence Interval |
(2-Sided) 95% -4.2 to 7.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Infect. & Infest. | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 4.1 | |
| Confidence Interval |
(2-Sided) 95% -3.6 to 12.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Infect. & Infest. | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -6.5 to 8.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Injury, poison. | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -7.3 to 5.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 1250mg - Placebo: Percentage Difference - Injury, poison. | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 1.6 | |
| Confidence Interval |
(2-Sided) 95% -5.0 to 8.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Investigations | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -9.8 to 7.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Investigations | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.9 | |
| Confidence Interval |
(2-Sided) 95% -10.5 to 6.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Nervous System | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -2.7 | |
| Confidence Interval |
(2-Sided) 95% -8.4 to 2.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Nervous System | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -2.7 | |
| Confidence Interval |
(2-Sided) 95% -8.4 to 2.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Psychiatric disorders | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -5.7 to 5.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Psychiatric disorders | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -5.7 to 5.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Renal & Urinary | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -7.2 to 3.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Renal & Urinary | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -7.2 to 3.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Resp. & chest | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -4.4 | |
| Confidence Interval |
(2-Sided) 95% -10.7 to 0.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Resp. & chest | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -8.4 to 4.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Skin & subcutan. | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 2.5 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to 8.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Skin & subcutan. | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% -4.7 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 250 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 250 mg - Placebo: Percentage Difference - Vascular disorders | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -3.6 | |
| Confidence Interval |
(2-Sided) 95% -9.9 to 2.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Relebactam 125 mg With Imipenem/Cilastatin, Placebo to Relebactam With Imipenem/Cilastatin |
|---|---|---|
| Comments | Relebactam 125 mg - Placebo: Percentage Difference - Vascular disorders | |
| Type of Statistical Test | Other | |
| Comments | Unconditional asymptotic Miettinen and Nurminen method without stratification | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -6.9 to 6.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Relebactam minus Placebo | |
Adverse Events
| Time Frame | 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) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||
| Arm/Group Title | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin | |||
| Arm/Group Description | Participants received relebactam 250 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | Participants received relebactam 125 mg IV with imipenem/cilastatin 500 mg IV every 6 hours for a minimum of 96 hours | 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 | |||
All Cause Mortality |
||||||
| Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/117 (0%) | 3/116 (2.6%) | 0/114 (0%) | |||
Serious Adverse Events |
||||||
| Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/117 (3.4%) | 13/116 (11.2%) | 8/114 (7%) | |||
| Blood and lymphatic system disorders | ||||||
| Thrombocytosis | 0/117 (0%) | 0 | 0/116 (0%) | 0 | 1/114 (0.9%) | 1 |
| Cardiac disorders | ||||||
| Cardiac failure chronic | 1/117 (0.9%) | 1 | 0/116 (0%) | 0 | 0/114 (0%) | 0 |
| Cardiac failure congestive | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Ventricular fibrillation | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Diarrhoea | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Ileus paralytic | 1/117 (0.9%) | 1 | 0/116 (0%) | 0 | 0/114 (0%) | 0 |
| Intestinal infarction | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Small intestinal obstruction | 0/117 (0%) | 0 | 0/116 (0%) | 0 | 1/114 (0.9%) | 1 |
| Intestinal obstruction | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Pancreatitis Acute | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholelithiasis obstructive | 0/117 (0%) | 0 | 0/116 (0%) | 0 | 1/114 (0.9%) | 1 |
| Infections and infestations | ||||||
| Abdominal abscess | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 1/114 (0.9%) | 1 |
| Clostridium difficile infection | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Liver abscess | 1/117 (0.9%) | 1 | 0/116 (0%) | 0 | 0/114 (0%) | 0 |
| Postoperative wound infection | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Septic shock | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Post procedural bile leak | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Procedural pain | 0/117 (0%) | 0 | 0/116 (0%) | 0 | 1/114 (0.9%) | 1 |
| Wound dehiscence | 0/117 (0%) | 0 | 0/116 (0%) | 0 | 1/114 (0.9%) | 1 |
| Wound evisceration | 1/117 (0.9%) | 1 | 0/116 (0%) | 0 | 0/114 (0%) | 0 |
| Suture rupture | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Benign gastrointestinal neoplasm | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Mucinous adenocarcinoma of appendix | 0/117 (0%) | 0 | 0/116 (0%) | 0 | 1/114 (0.9%) | 1 |
| Nervous system disorders | ||||||
| Cerebrovascular accident | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Renal failure acute | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory failure | 0/117 (0%) | 0 | 0/116 (0%) | 0 | 1/114 (0.9%) | 1 |
| Lung consolidation | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Pleural effusion | 0/117 (0%) | 0 | 1/116 (0.9%) | 1 | 0/114 (0%) | 0 |
| Pulmonary embolism | 0/117 (0%) | 0 | 0/116 (0%) | 0 | 2/114 (1.8%) | 2 |
Other (Not Including Serious) Adverse Events |
||||||
| Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Placebo to Relebactam With Imipenem/Cilastatin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/117 (13.7%) | 15/116 (12.9%) | 13/114 (11.4%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 7/117 (6%) | 8 | 6/116 (5.2%) | 6 | 5/114 (4.4%) | 5 |
| Nausea | 8/117 (6.8%) | 9 | 9/116 (7.8%) | 9 | 8/114 (7%) | 9 |
| Vomiting | 7/117 (6%) | 7 | 9/116 (7.8%) | 9 | 3/114 (2.6%) | 3 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01506271
Other Study ID Numbers:
- 7655-004
- 2011-005686-20
- MK-7655-004
First Posted:
Jan 9, 2012
Last Update Posted:
Jun 10, 2019
Last Verified:
Jun 1, 2019