Suspected or Documented Gram-negative Bacterial Infection
Conditions
Brief summary
The primary purpose of this study is to evaluate the safety and tolerability of imipenem/cilastatin/relebactam (IMI/REL) in participants from birth to less than 18 years of age with confirmed or suspected gram-negative bacterial infection. Participants are expected to require hospitalization through completion of intravenous (IV) study intervention, and have at least one of the following primary infection types: hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP); complicated intra-abdominal infection (cIAI); or complicated urinary tract infection (cUTI). Participants will be randomized in a 3:1 ratio to receive IMI/REL or active control. This study will also evaluate the efficacy of IMI/REL by assessing all-cause mortality at Day 28 post-randomization, as well as clinical and microbiological response to treatment. It will also evaluate the pharmacokinetics of IMI/REL.
Interventions
DRUGIMI/REL
Age-based dosing: * 12 to \<18 years, IMI 500 and REL 250 mg, IV infusion every 6 hours * 6 to \<12 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours * 2 to \<6 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours * 3 months to \<2 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours * Birth to \<3 months, IMI 15 and REL 7.5 mg/kg, IV infusion every 8 hours NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention.
DRUGActive Control
All active control medications will be chosen from a list of acceptable approved agents for each infection type (HABP or VABP, cIAI, and UTI) and will be given via IV infusion, per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention. All oral switch medications will be chosen from a list of acceptable approved agents.
DRUGOral Switch
All oral switch medications will be investigator's choice from a list of acceptable approved agents for infection types cIAI, and cUTI and will be given per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria include but are not limited to: * Requires hospitalization and treatment with intravenous (IV) antibacterial therapy for confirmed or suspected gram-negative bacterial infection (in the absence of meningitis), and is expected to require hospitalization through completion of IV study intervention, with at least 1 of the following primary infection types: Hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP); complicated intra-abdominal infection (cIAI); or complicated urinary tract infection (cUTI). * For Age Cohorts 4 and 5, participant is at least 37 weeks postmenstrual age at the time of signing the informed consent/assent. * If female, must not be pregnant or breastfeeding, and at least 1 of the following conditions must apply: must not be a woman of childbearing potential (WOCBP); OR, if a WOCBP, must agree to follow contraceptive guidance during the intervention period and for at least 24 hours after the last dose of study intervention. * Has sufficient intravascular access to receive study drug through an existing peripheral or central line.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With One or More Adverse Event (AE) | Up to 28 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with AEs are presented. |
| Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | Up to 14 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study medication due to an AE are presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With All-cause Mortality Through Day 28 | Up to Day 28 | For each participant, survival status was assessed at Day 28 post-randomization. The percentage of participants with all-cause mortality through Day 28 is presented. |
| Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | Day 5 up to Day 14 | A favorable clinical response at EOT requires an assessment of "cure" or "improved". Cure is defined as all preintervention signs and symptoms of the index infection have resolved (or returned to "preinfection status", with no new symptoms) AND no additional antibacterial intervention is required for the index infection. Improved is defined as the majority of preintervention signs and symptoms of the index infection have improved or resolved (or returned to "preinfection status", with no new symptoms) AND no additional antibacterial intervention is required. The percentage of participants with a favorable clinical response at EOT is presented. |
| Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | Day 12 up to Day 28 | A favorable clinical response at EFU requires an assessment of "cure" or "sustained cure". Cure is defined as all preintervention signs and symptoms of the index infection have resolved (or returned to "preinfection status", with no new symptoms) AND no additional antibacterial intervention is required for the index infection. Sustained cure is defined as a clinical response for the prior visit (EOT or EFU) being defined as "cure". The percentage of participants with a favorable clinical response at EFU is presented. |
| Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | Baseline and Day 19 up to Day 42 | A favorable clinical response at LFU requires an assessment of "cure" or "sustained cure". Cure is defined as all preintervention signs and symptoms of the index infection have resolved (or returned to "preinfection status", with no new symptoms) AND no additional antibacterial intervention is required for the index infection. Sustained cure is defined as a clinical response for the prior visit (EOT or EFU) being defined as "cure". The percentage of participants with a favorable clinical response at LFU is presented. |
| Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | Day 5 up to Day 14 | A favorable microbial response is defined as eradication or presumed eradication. Eradication is defined as one of the following: A lower respiratory tract culture taken at the EOT visit shows eradication of the pathogen found at study entry for HABP/VABP; An intra-abdominal culture taken at the EOT visit shows eradication of the pathogen found at study entry for cIAI; A urine culture taken at the EOT visit shows eradication of the uropathogen (reduced to \<103 CFU/mL) found at study entry for cUTI. Presumed eradication is defined as no specimen taken because participant is deemed clinically improved or cured of the pathogen found at study entry. The percentage of participants with a favorable microbial response at EOT is presented. |
| Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | Day 12 up to Day 28 | A favorable microbiological response at EFU is defined as eradication or presumed eradication. Eradication is defined as one of the following: A lower respiratory tract culture taken at the EFU visit shows eradication of the pathogen found at study entry for HABP/VABP; An intra-abdominal culture taken at the EFU visit shows eradication of the pathogen found at study entry for cIAI; A urine culture taken at the EFU visit shows eradication of the uropathogen (reduced to \<103 CFU/mL) found at study entry for cUTI. Presumed eradication is defined as no specimen taken because participant is deemed clinically improved or cured of the pathogen found at study entry. The percentage of participants with a favorable microbial response at EFU is presented. |
| Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | Day 19 up to Day 42 | A favorable microbiological response at LFU is defined as eradication or presumed eradication. Eradication is defined as one of the following: A lower respiratory tract culture taken at the LFU visit shows eradication of the pathogen found at study entry for HABP/VABP; An intra-abdominal culture taken at the LFU visit shows eradication of the pathogen found at study entry for cIAI; A urine culture taken at the LFU visit shows eradication of the uropathogen (reduced to \<103 CFU/mL) found at study entry for cUTI. Presumed eradication is defined as no specimen taken because participant is deemed clinically improved or cured of the pathogen found at study entry. The percentage of participants with a favorable microbial response at LFU is presented. |
| Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Imipenem Following Administration of IMI/REL | On Day 1 at 30 minutes prior to start of first IV infusion of study drug, at end of first infusion, and 2 to 6 hours after start of first infusion; and once at on-therapy visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day. | AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Blood samples were collected to determine the AUC0-24 of imipenem. |
| Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Relebactam Following Administration of IMI/REL | On Day 1 at 30 minutes prior to start of first IV infusion of study drug, at end of first infusion, and 2 to 6 hours after start of first infusion; and once at on-therapy visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day. | AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Blood samples were collected to determine the AUC0-24 of relebactam. |
| Concentration at End of Infusion (Ceoi) of Imipenem Following Administration of IMI/REL | At the end of the first infusion on Day 1. | Ceoi is the concentration of the drug at the end of infusion. Blood samples for analysis were collected within 10 minutes of the end of infusion to determine the Ceoi of imipenem. |
| Concentration at End of Infusion (Ceoi) of Relebactam Following Administration of IMI/REL | At the end of the first infusion on Day 1. | Ceoi is the concentration of the drug at the end of infusion. Blood samples for analysis were collected within 10 minutes of the end of infusion to determine the Ceoi of relebactam. |
| Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T>MIC of Imipenem) Following Administration of IMI/REL | On Day 1 at 30 minutes prior to start of first IV infusion of study drug, at end of first infusion, and 2 to 6 hours after start of first infusion; and once at on-therapy visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day. | Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T\>MIC) is defined as the cumulative percentage the drug concentration exceeds the MIC at steady state pharmacokinetic conditions. Blood samples were collected to determine %T\>MIC of imipenem. %T\>MIC is calculated using baseline microbiological response values. |
Countries
Bulgaria, Chile, Colombia, Estonia, France, Greece, Hungary, Israel, Mexico, Norway, Philippines, Poland, Russia, South Africa, Spain, Turkey (Türkiye), Ukraine, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) Participants with cIAI and complicated urinary tract infection cUTI received IMI/REL fixed-dose combination of 500 mg/250 mg via IV infusion every 6 hours for a minimum of 5 days with an option of investigator's choice of locally sourced oral switch medication after a minimum of 3 days of IV therapy alone. Participants with HABP/VABP received IMI/REL fixed-dose combination of 500 mg/250 mg via IV infusion every 6 hours for 7 days up to 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received IMI/REL fixed-dose combination of 500 mg/250 mg via IV infusion every 6 hours for 14 days. All oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All oral switch medications were chosen from a list of acceptable approved agents. | 10 |
| Active Control Age Cohort 1: Adolescents (12 to <18 Years) Participants with cIAI or cUTI received investigator's choice of locally sourced active control via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days of IV therapy alone) up to a maximum of 14 days. Participants with HABP/VABP received investigator's choice of locally sourced active control via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received investigator's choice of locally sourced active control via IV infusion for 14 days. All active control and oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All active control and oral switch medications were chosen from a list of acceptable approved agents. | 2 |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) Participants with cIAI and cUTI received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 6 hours for a minimum of 5 days with an option of investigator's choice of locally sourced oral switch medication after a minimum of 3 days of IV therapy alone. Participants with HABP/VABP received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 6 hours for 7 days up to 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 6 hours for 14 days. All oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All oral switch medications were chosen from a list of acceptable approved agents. | 31 |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) Participants with cIAI or cUTI received investigator's choice of locally sourced active control via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days of IV therapy alone) up to a maximum of 14 days. Participants with HABP/VABP received investigator's choice of locally sourced active control via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received investigator's choice of locally sourced active control via IV infusion for 14 days. All active control and oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All active control and oral switch medications were chosen from a list of acceptable approved agents. | 11 |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) Participants with cIAI and cUTI received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 6 hours for a minimum of 5 days with an option of investigator's choice of locally sourced oral switch medication after a minimum of 3 days of IV therapy alone. Participants with HABP/VABP received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 6 hours for 7 days up to 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 6 hours for 14 days. All oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All oral switch medications were chosen from a list of acceptable approved agents. | 22 |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) Participants with cIAI or cUTI received investigator's choice of locally sourced active control via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days of IV therapy alone) up to a maximum of 14 days. Participants with HABP/VABP received investigator's choice of locally sourced active control via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received investigator's choice of locally sourced active control via IV infusion for 14 days. All active control and oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All active control and oral switch medications were chosen from a list of acceptable approved agents. | 8 |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) Participants with cIAI and cUTI received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 6 hours for a minimum of 5 days with an option of investigator's choice of locally sourced oral switch medication after a minimum of 3 days of IV therapy alone. Participants with HABP/VABP received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 6 hours for 7 days up to 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 6 hours for 14 days. All oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All oral switch medications were chosen from a list of acceptable approved agents. | 15 |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) Participants with cIAI or cUTI received investigator's choice of locally sourced active control via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days of IV therapy alone) up to a maximum of 14 days. Participants with HABP/VABP received investigator's choice of locally sourced active control via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received investigator's choice of locally sourced active control via IV infusion for 14 days. All active control and oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All active control and oral switch medications were chosen from a list of acceptable approved agents. | 5 |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) Participants with cIAI and cUTI received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 8 hours for a minimum of 5 days with an option of investigator's choice of locally sourced oral switch medication after a minimum of 3 days of IV therapy alone. Participants with HABP/VABP received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 8 hours for 7 days up to 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received IMI/REL fixed-dose combination of 15 mg/7.5 mg via IV infusion every 8 hours for 14 days. All oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All oral switch medications were chosen from a list of acceptable approved agents. | 8 |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) Participants with cIAI or cUTI received investigator's choice of locally sourced active control via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days of IV therapy alone) up to a maximum of 14 days. Participants with HABP/VABP received investigator's choice of locally sourced active control via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection received investigator's choice of locally sourced active control via IV infusion for 14 days. All active control and oral switch medications were administered per authorized PI, SPC, or international treatment guidelines. All active control and oral switch medications were chosen from a list of acceptable approved agents. | 3 |
| Total | 115 |
Baseline characteristics
| Characteristic | IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Active Control Age Cohort 1: Adolescents (12 to <18 Years) | IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Active Control Age Cohort 2: Older Children (6 to <12 Years) | IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Active Control Age Cohort 3: Younger Children (2 to <6 Years) | IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 15.1 Years STANDARD_DEVIATION 2 | 16.5 Years STANDARD_DEVIATION 0.7 | 8.4 Years STANDARD_DEVIATION 1.7 | 8.0 Years STANDARD_DEVIATION 1.7 | 3.5 Years STANDARD_DEVIATION 1.1 | 4.3 Years STANDARD_DEVIATION 1.2 | 0.9 Years STANDARD_DEVIATION 0.5 | 0.7 Years STANDARD_DEVIATION 0.6 | 0.1 Years STANDARD_DEVIATION 0.1 | 0.1 Years STANDARD_DEVIATION 0.1 | 5.8 Years STANDARD_DEVIATION 4.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 9 Participants | 1 Participants | 12 Participants | 4 Participants | 5 Participants | 1 Participants | 3 Participants | 2 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 1 Participants | 21 Participants | 10 Participants | 10 Participants | 4 Participants | 9 Participants | 4 Participants | 5 Participants | 1 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Infection Type cIAI | 5 Participants | 1 Participants | 21 Participants | 7 Participants | 14 Participants | 5 Participants | 0 Participants | 1 Participants | 0.0 Participants | 0.0 Participants | 54 Participants |
| Infection Type cUTI | 4 Participants | 1 Participants | 10 Participants | 4 Participants | 6 Participants | 2 Participants | 14 Participants | 4 Participants | 7 Participants | 3 Participants | 55 Participants |
| Infection Type HABP/VABP | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 1 Participants | 27 Participants | 10 Participants | 19 Participants | 4 Participants | 11 Participants | 5 Participants | 8 Participants | 2 Participants | 94 Participants |
| Sex: Female, Male Female | 8 Participants | 1 Participants | 13 Participants | 8 Participants | 12 Participants | 3 Participants | 7 Participants | 1 Participants | 3 Participants | 0 Participants | 56 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 18 Participants | 3 Participants | 10 Participants | 5 Participants | 8 Participants | 4 Participants | 5 Participants | 3 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 2 | 0 / 31 | 0 / 11 | 0 / 22 | 0 / 8 | 0 / 15 | 0 / 5 | 0 / 8 | 0 / 3 |
| other Total, other adverse events | 6 / 10 | 1 / 2 | 17 / 31 | 3 / 11 | 13 / 21 | 5 / 8 | 12 / 15 | 2 / 4 | 2 / 8 | 1 / 3 |
| serious Total, serious adverse events | 0 / 10 | 0 / 2 | 6 / 31 | 1 / 11 | 0 / 21 | 0 / 8 | 4 / 15 | 1 / 4 | 0 / 8 | 1 / 3 |
Outcome results
Primary
Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study medication due to an AE are presented.
Time frame: Up to 14 days
Population: All randomized participants who received at least 1 dose of IV study intervention. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 12.9 Percentage of Participants |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 9.1 Percentage of Participants |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 6.7 Percentage of Participants |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 25.0 Percentage of Participants |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
Primary
Percentage of Participants With One or More Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with AEs are presented.
Time frame: Up to 28 days
Population: All randomized participants who received at least 1 dose of IV study intervention. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Participants With One or More Adverse Event (AE) | 60.0 Percentage of Participants |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Participants With One or More Adverse Event (AE) | 50.0 Percentage of Participants |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With One or More Adverse Event (AE) | 64.5 Percentage of Participants |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With One or More Adverse Event (AE) | 36.4 Percentage of Participants |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With One or More Adverse Event (AE) | 71.4 Percentage of Participants |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With One or More Adverse Event (AE) | 62.5 Percentage of Participants |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With One or More Adverse Event (AE) | 93.3 Percentage of Participants |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With One or More Adverse Event (AE) | 50.0 Percentage of Participants |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With One or More Adverse Event (AE) | 25.0 Percentage of Participants |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With One or More Adverse Event (AE) | 66.7 Percentage of Participants |
Secondary
Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Imipenem Following Administration of IMI/REL
AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Blood samples were collected to determine the AUC0-24 of imipenem.
Time frame: On Day 1 at 30 minutes prior to start of first IV infusion of study drug, at end of first infusion, and 2 to 6 hours after start of first infusion; and once at on-therapy visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Population: The analysis population includes all participants who received at least 1 dose of IMI/REL and had at least one measurable pharmacokinetic (PK) sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Imipenem Following Administration of IMI/REL | 610 µM*hr | Geometric Coefficient of Variation 55.5 |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Imipenem Following Administration of IMI/REL | 720 µM*hr | Geometric Coefficient of Variation 25.8 |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Imipenem Following Administration of IMI/REL | 692 µM*hr | Geometric Coefficient of Variation 23.5 |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Imipenem Following Administration of IMI/REL | 788 µM*hr | Geometric Coefficient of Variation 28.4 |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Imipenem Following Administration of IMI/REL | 795 µM*hr | Geometric Coefficient of Variation 19.5 |
Secondary
Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Relebactam Following Administration of IMI/REL
AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Blood samples were collected to determine the AUC0-24 of relebactam.
Time frame: On Day 1 at 30 minutes prior to start of first IV infusion of study drug, at end of first infusion, and 2 to 6 hours after start of first infusion; and once at on-therapy visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Population: The analysis population includes all participants who received at least 1 dose of IMI/REL and had at least one measurable pharmacokinetic (PK) sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Relebactam Following Administration of IMI/REL | 399 µM*hr | Geometric Coefficient of Variation 64 |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Relebactam Following Administration of IMI/REL | 469 µM*hr | Geometric Coefficient of Variation 30.9 |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Relebactam Following Administration of IMI/REL | 459 µM*hr | Geometric Coefficient of Variation 30.4 |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Relebactam Following Administration of IMI/REL | 634 µM*hr | Geometric Coefficient of Variation 56.8 |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Relebactam Following Administration of IMI/REL | 605 µM*hr | Geometric Coefficient of Variation 50.1 |
Secondary
Concentration at End of Infusion (Ceoi) of Imipenem Following Administration of IMI/REL
Ceoi is the concentration of the drug at the end of infusion. Blood samples for analysis were collected within 10 minutes of the end of infusion to determine the Ceoi of imipenem.
Time frame: At the end of the first infusion on Day 1.
Population: The analysis population includes all participants who received at least 1 dose of IMI/REL and had at least one measurable pharmacokinetic (PK) sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Concentration at End of Infusion (Ceoi) of Imipenem Following Administration of IMI/REL | 79.2 µM | Geometric Coefficient of Variation 17.6 |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Concentration at End of Infusion (Ceoi) of Imipenem Following Administration of IMI/REL | 103 µM | Geometric Coefficient of Variation 15 |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Concentration at End of Infusion (Ceoi) of Imipenem Following Administration of IMI/REL | 101 µM | Geometric Coefficient of Variation 12.7 |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Concentration at End of Infusion (Ceoi) of Imipenem Following Administration of IMI/REL | 109 µM | Geometric Coefficient of Variation 14.1 |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Concentration at End of Infusion (Ceoi) of Imipenem Following Administration of IMI/REL | 117 µM | Geometric Coefficient of Variation 5.51 |
Secondary
Concentration at End of Infusion (Ceoi) of Relebactam Following Administration of IMI/REL
Ceoi is the concentration of the drug at the end of infusion. Blood samples for analysis were collected within 10 minutes of the end of infusion to determine the Ceoi of relebactam.
Time frame: At the end of the first infusion on Day 1.
Population: The analysis population includes all participants who received at least 1 dose of IMI/REL and had at least one measurable pharmacokinetic (PK) sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Concentration at End of Infusion (Ceoi) of Relebactam Following Administration of IMI/REL | 43.4 µM | Geometric Coefficient of Variation 28.6 |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Concentration at End of Infusion (Ceoi) of Relebactam Following Administration of IMI/REL | 56.1 µM | Geometric Coefficient of Variation 18.6 |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Concentration at End of Infusion (Ceoi) of Relebactam Following Administration of IMI/REL | 56.1 µM | Geometric Coefficient of Variation 16.2 |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Concentration at End of Infusion (Ceoi) of Relebactam Following Administration of IMI/REL | 67.1 µM | Geometric Coefficient of Variation 27.4 |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Concentration at End of Infusion (Ceoi) of Relebactam Following Administration of IMI/REL | 67.9 µM | Geometric Coefficient of Variation 22.2 |
Secondary
Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU)
A favorable clinical response at EFU requires an assessment of cure or sustained cure. Cure is defined as all preintervention signs and symptoms of the index infection have resolved (or returned to preinfection status, with no new symptoms) AND no additional antibacterial intervention is required for the index infection. Sustained cure is defined as a clinical response for the prior visit (EOT or EFU) being defined as cure. The percentage of participants with a favorable clinical response at EFU is presented.
Time frame: Day 12 up to Day 28
Population: The analysis population included all randomized participants who received at least 1 dose of IV study intervention. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 90.0 Percentage of Participants |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 50.0 Percentage of Participants |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 77.4 Percentage of Participants |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 81.8 Percentage of Participants |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 85.7 Percentage of Participants |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 87.5 Percentage of Participants |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 26.7 Percentage of Participants |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 75.0 Percentage of Participants |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 62.5 Percentage of Participants |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU) | 33.3 Percentage of Participants |
Secondary
Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT)
A favorable clinical response at EOT requires an assessment of cure or improved. Cure is defined as all preintervention signs and symptoms of the index infection have resolved (or returned to preinfection status, with no new symptoms) AND no additional antibacterial intervention is required for the index infection. Improved is defined as the majority of preintervention signs and symptoms of the index infection have improved or resolved (or returned to preinfection status, with no new symptoms) AND no additional antibacterial intervention is required. The percentage of participants with a favorable clinical response at EOT is presented.
Time frame: Day 5 up to Day 14
Population: The analysis population included all randomized participants who received at least 1 dose of IV study intervention. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 90.0 Percentage of Participants |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 50.0 Percentage of Participants |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 77.4 Percentage of Participants |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 81.8 Percentage of Participants |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 90.5 Percentage of Participants |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 87.5 Percentage of Participants |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 53.3 Percentage of Participants |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 75.0 Percentage of Participants |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 87.5 Percentage of Participants |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT) | 33.3 Percentage of Participants |
Secondary
Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU)
A favorable clinical response at LFU requires an assessment of cure or sustained cure. Cure is defined as all preintervention signs and symptoms of the index infection have resolved (or returned to preinfection status, with no new symptoms) AND no additional antibacterial intervention is required for the index infection. Sustained cure is defined as a clinical response for the prior visit (EOT or EFU) being defined as cure. The percentage of participants with a favorable clinical response at LFU is presented.
Time frame: Baseline and Day 19 up to Day 42
Population: The analysis population included all randomized participants who received at least 1 dose of IV study intervention. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 90.0 Percentage of Participants |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 50.0 Percentage of Participants |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 74.2 Percentage of Participants |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 81.8 Percentage of Participants |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 81.0 Percentage of Participants |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 87.5 Percentage of Participants |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 33.3 Percentage of Participants |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 75.0 Percentage of Participants |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 62.5 Percentage of Participants |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU) | 33.3 Percentage of Participants |
Secondary
Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU)
A favorable microbiological response at EFU is defined as eradication or presumed eradication. Eradication is defined as one of the following: A lower respiratory tract culture taken at the EFU visit shows eradication of the pathogen found at study entry for HABP/VABP; An intra-abdominal culture taken at the EFU visit shows eradication of the pathogen found at study entry for cIAI; A urine culture taken at the EFU visit shows eradication of the uropathogen (reduced to \<103 CFU/mL) found at study entry for cUTI. Presumed eradication is defined as no specimen taken because participant is deemed clinically improved or cured of the pathogen found at study entry. The percentage of participants with a favorable microbial response at EFU is presented.
Time frame: Day 12 up to Day 28
Population: For participants with HABP/VABP and cIAI: Has received at least 1 dose of IV study intervention; AND baseline infection-site culture grew at least 1 gram-negative pathogenic organism. For participants with cUTI: Has received at least 1 dose of IV study intervention; AND baseline urine culture grew at least 1 gram-negative pathogenic organism at sufficient quantity (ie, growth at ≥105 CFU/mL of uropathogen). Participants were included in the intervention group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 71.4 Percentage of Participants |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 100.0 Percentage of Participants |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 96.3 Percentage of Participants |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 100.0 Percentage of Participants |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 93.8 Percentage of Participants |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 100.0 Percentage of Participants |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 63.6 Percentage of Participants |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 75.0 Percentage of Participants |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 71.4 Percentage of Participants |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU) | 50.0 Percentage of Participants |
Secondary
Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT)
A favorable microbial response is defined as eradication or presumed eradication. Eradication is defined as one of the following: A lower respiratory tract culture taken at the EOT visit shows eradication of the pathogen found at study entry for HABP/VABP; An intra-abdominal culture taken at the EOT visit shows eradication of the pathogen found at study entry for cIAI; A urine culture taken at the EOT visit shows eradication of the uropathogen (reduced to \<103 CFU/mL) found at study entry for cUTI. Presumed eradication is defined as no specimen taken because participant is deemed clinically improved or cured of the pathogen found at study entry. The percentage of participants with a favorable microbial response at EOT is presented.
Time frame: Day 5 up to Day 14
Population: For participants with HABP/VABP and cIAI: Has received at least 1 dose of IV study intervention; AND baseline infection-site culture grew at least 1 gram-negative pathogenic organism. For participants with cUTI: Has received at least 1 dose of IV study intervention; AND baseline urine culture grew at least 1 gram-negative pathogenic organism at sufficient quantity (ie, growth at ≥105 CFU/mL of uropathogen). Participants were included in the intervention group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 100.0 Percentage of Participants |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 100.0 Percentage of Participants |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 100.0 Percentage of Participants |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 100.0 Percentage of Participants |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 100.0 Percentage of Participants |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 100.0 Percentage of Participants |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 72.7 Percentage of Participants |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 75.0 Percentage of Participants |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 100.0 Percentage of Participants |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT) | 50.0 Percentage of Participants |
Secondary
Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU)
A favorable microbiological response at LFU is defined as eradication or presumed eradication. Eradication is defined as one of the following: A lower respiratory tract culture taken at the LFU visit shows eradication of the pathogen found at study entry for HABP/VABP; An intra-abdominal culture taken at the LFU visit shows eradication of the pathogen found at study entry for cIAI; A urine culture taken at the LFU visit shows eradication of the uropathogen (reduced to \<103 CFU/mL) found at study entry for cUTI. Presumed eradication is defined as no specimen taken because participant is deemed clinically improved or cured of the pathogen found at study entry. The percentage of participants with a favorable microbial response at LFU is presented.
Time frame: Day 19 up to Day 42
Population: For participants with HABP/VABP and cIAI: Has received at least 1 dose of IV study intervention; AND baseline infection-site culture grew at least 1 gram-negative pathogenic organism. For participants with cUTI: Has received at least 1 dose of IV study intervention; AND baseline urine culture grew at least 1 gram-negative pathogenic organism at sufficient quantity (ie, growth at ≥105 CFU/mL of uropathogen). Participants were included in the intervention group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 85.7 Percentage of Participants |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 0.0 Percentage of Participants |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 96.3 Percentage of Participants |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 100.0 Percentage of Participants |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 87.5 Percentage of Participants |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 100.0 Percentage of Participants |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 72.7 Percentage of Participants |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 75.0 Percentage of Participants |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 71.4 Percentage of Participants |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU) | 50.0 Percentage of Participants |
Secondary
Percentage of Participants With All-cause Mortality Through Day 28
For each participant, survival status was assessed at Day 28 post-randomization. The percentage of participants with all-cause mortality through Day 28 is presented.
Time frame: Up to Day 28
Population: The analysis population included all randomized participants who received at least 1 dose of IV study intervention. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
| Active Control Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
| IMI/REL Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
| Active Control Age Cohort 4: Infants and Toddlers (3 Months to <2 Years) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
| IMI/REL Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
| Active Control Age Cohort 5: Neonates and Young Infants (Birth to <3 Months) | Percentage of Participants With All-cause Mortality Through Day 28 | 0.0 Percentage of Participants |
Secondary
Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T>MIC of Imipenem) Following Administration of IMI/REL
Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T\>MIC) is defined as the cumulative percentage the drug concentration exceeds the MIC at steady state pharmacokinetic conditions. Blood samples were collected to determine %T\>MIC of imipenem. %T\>MIC is calculated using baseline microbiological response values.
Time frame: On Day 1 at 30 minutes prior to start of first IV infusion of study drug, at end of first infusion, and 2 to 6 hours after start of first infusion; and once at on-therapy visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Population: The analysis population includes all participants who received at least 1 dose of IMI/REL and had at least one measurable pharmacokinetic (PK) sample for %T\>MIC.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMI/REL Age Cohort 1: Adolescents (12 to <18 Years) | Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T>MIC of Imipenem) Following Administration of IMI/REL | 100.0 Percentage of time | Standard Deviation 0 |
| Active Control Cohort 1: Adolescents: (12 to <18 Years) | Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T>MIC of Imipenem) Following Administration of IMI/REL | 93.4 Percentage of time | Standard Deviation 22.1 |
| IMI/REL Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T>MIC of Imipenem) Following Administration of IMI/REL | 83.6 Percentage of time | Standard Deviation 23.1 |
| Active Control Age Cohort 2: Older Children (6 to <12 Years) | Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T>MIC of Imipenem) Following Administration of IMI/REL | 79.6 Percentage of time | Standard Deviation 35.3 |
| IMI/REL Age Cohort 3: Younger Children (2 to <6 Years) | Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T>MIC of Imipenem) Following Administration of IMI/REL | 83.5 Percentage of time | Standard Deviation 25.6 |