Safety, Tolerability, Efficacy and Pharmacokinetics of Imipenem/Cilastatin/Relebactam (MK-7655A) in Pediatric Participants With Gram-negative Bacterial Infection (MK-7655A-021)

A Phase 2/3 Open-label, Randomized, Active-controlled Clinical Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of MK-7655A in Pediatric Participants From Birth to Less Than 18 Years of Age With Confirmed or Suspected Gram-negative Bacterial Infection

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.

Study Overview

• Status: Completed
• Conditions: Suspected or Documented Gram-negative Bacterial Infection
• Intervention / Treatment: Drug: Active Control; Drug: IMI/REL; Drug: Oral Switch

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8127
    • UMHAT Deva Maria. EOOD ( Site 0165)
  • Montana, Bulgaria, 3400
    • MHAT City Clinic Sv. Georgi EOOD ( Site 0167)
  • Pleven, Bulgaria, 5800
    • UMHAT Dr. Georgi Stranski EAD ( Site 0174)
  • Rousse, Bulgaria, 7002
    • UMHAT Kanev AD ( Site 0168)
  • Rousse, Bulgaria, 7002
    • UMHAT Kanev AD ( Site 0169)
  • Sliven, Bulgaria, 8800
    • MHAT Dr. Ival Seliminski ( Site 0173)
• Chile
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 8380418
      • Hospital Roberto del Río ( Site 0802)
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050010
      • Fundacion Hospital San Vicente de Paul ( Site 0269)
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 080020
      • Clinica de la Costa S.A.S. ( Site 0264)
  • Bogota D.C.
    • Bogotá, Bogota D.C., Colombia, 11001000
      • Sociedad de Cirugía de Bogotá - Hospital de San Jose ( Site 0265)
    • Bogotá, Bogota D.C., Colombia, 111211
      • Fundacion Hospital Infantil Universitario de San Jose ( Site 0268)
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760032
      • Fundacion Valle del Lili ( Site 0266)
• Estonia
  • Harju
    • Tallinn, Harju, Estonia, 13419
      • Tallinn Children Hospital ( Site 0209)
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06200
      • Hopitaux Pediatriques CHU Lenval ( Site 0143)
  • Cote-d Or
    • Dijon, Cote-d Or, France, 21000
      • Hopital Francois Mitterand ( Site 0146)
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59120
      • Hopital Jeanne de Flandre ( Site 0145)
• Greece
  • Thessaloniki, Greece, 546 42
    • Hippokration General Hospital of Thessaloniki ( Site 0244)
  • Attica
    • Athens, Attica, Greece, 115 27
      • University of Athens - Aghia Sophia Childrens Hospital ( Site 0243)
    • Athens, Attica, Greece, 11527
      • Pan and Aglaia Kyriakou Children s Hospital ( Site 0247)
• Hungary
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary, 4032
      • Debreceni Egyetem Klinikai Kozpont ( Site 0100)
  • Szabolcs-Szatmár-Bereg
    • Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, 4400
      • Szabolcs-Szatmar-Bereg Megyei Kórházak és Egyetemi Otatókórház-Gyermekosztály ( Site 0105)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center ( Site 0189)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Karem Hebrew University Medical Center ( Site 0188)
  • Petah Tikva, Israel, 4920235
    • Schneider Children's Medical Center ( Site 0187)
  • Ramat Gan, Israel, 5262100
    • Chaim Sheba Medical Center ( Site 0190)
• Mexico
  • Aguascalientes, Mexico, 20259
    • Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 0290)
  • Mexico City, Mexico, 04530
    • Instituto Nacional de Pediatria ( Site 0291)
  • Estado de Baja California
    • Tijuana, Estado de Baja California, Mexico, 22000
      • Hospital General de Tijuana ( Site 0284)
  • Morelos
    • Emiliano Zapata, Morelos, Mexico, 62765
      • Hospital del Nino y Adolescente Morelense ( Site 0286)
• Norway
  • Hordaland
    • Bergen, Hordaland, Norway, 5009
      • Haukeland Universitetssjukehus ( Site 0500)
• Philippines
  • National Capital Region
    • Manila, National Capital Region, Philippines, 1000
      • University of the Philippines-Philippine General Hospital ( Site 0318)
    • Quezon City, National Capital Region, Philippines, 1104
      • Philippine Children s Medical Center ( Site 0317)
• Poland
  • Kuyavian-Pomeranian Voivodeship
    • Torun, Kuyavian-Pomeranian Voivodeship, Poland, 87-100
      • Wojewodzki Szpital Zespolony im. Rydgiera ( Site 0220)
  • Masovian Voivodeship
    • Łomianki, Masovian Voivodeship, Poland, 05-092
      • SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0226)
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 93-338
      • Instytut Centrum Zdrowia Matki Polki ( Site 0223)
• Russia
  • Moscow
    • Moscow, Moscow, Russia, 117197
      • Pediatric Hematology Oncology and Immunology Centre n.a. D.Rogachev. ( Site 0233)
    • Moscow, Moscow, Russia, 119049
      • Morozovskaya Children City Clinical Hospital ( Site 0241)
  • Novosibirsk Oblast
    • Novosibirsk, Novosibirsk Oblast, Russia, 630011
      • State Budgetary Healthcare Institution of Novosibirsk Region City Childrens Clinical Emergency Hospi
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 192289
      • Children s City Clinical Hospital 5 n.a. N.F. Filatov ( Site 0235)
    • Saint Petersburg, Sankt-Peterburg, Russia, 194100
      • St.Petersburg State Pediatric Medical University ( Site 0236)
    • Saint Petersburg, Sankt-Peterburg, Russia, 198205
      • Children's City Clinical Hospital #1 ( Site 0237)
  • Smolensk Oblast
    • Smolensk, Smolensk Oblast, Russia, 214018
      • Smolensk Regional Clinical Hospital ( Site 0231)
  • Vologda Oblast
    • Vologda, Vologda Oblast, Russia, 160022
      • Regional Childrens Clinical Hospital ( Site 0400)
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2001
      • Empilweni Services and Research Unit ( Site 1557)
    • Johannesburg, Gauteng, South Africa, 2013
      • Chris Hani Baragwanath Academic Hospital ( Site 0156)
    • Pretoria, Gauteng, South Africa, 0208
      • Molotlegi Street ( Site 0155)
• Spain
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus ( Site 0114)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0113)
  • Seville, Spain, 41043
    • Hospital Universitario Virgen del Rocio ( Site 0115)
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01330
    • Cukurova University Medical Faculty ( Site 0200)
  • Ankara, Turkey (Türkiye), 06590
    • Ankara Universitesi Tip Fakultesi. ( Site 0202)
  • Eskişehir, Turkey (Türkiye), 26480
    • Eskisehir Osmangazi University Medical ( Site 0201)
  • Istanbul, Turkey (Türkiye), 34453
    • SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 0198)
  • Izmir, Turkey (Türkiye), 35100
    • Ege Universitesi Tıp Fakultesi Hastanesi ( Site 0199)
• Ukraine
  • Dnipropetrovsk Oblast
    • Dnipro, Dnipropetrovsk Oblast, Ukraine, 49100
      • SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 0121)
    • Kryvyy Rig, Dnipropetrovsk Oblast, Ukraine, 50082
      • Communal non-commercial enterprise "Kryvorizka city clinical hospital 16" of Kryvyy Rig city council
  • Ivano-Frankivsk Oblast
    • Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76014
      • Ivano-Frankivsk Regional Children Clinical Hospital ( Site 0131)
  • Kharkivs’ka Oblast’
    • Kharkiv, Kharkivs’ka Oblast’, Ukraine, 61075
      • Kharkiv City Children Hospital 16 ( Site 0130)
  • Poltava Oblast
    • Poltava, Poltava Oblast, Ukraine, 36004
      • Municipal Enterprise Children's City Clinical Hospital in Poltava City Council ( Site 0122)
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Banner University Medical Center ( Site 0356)
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's & Women's Hospital ( Site 0349)
    • San Diego, California, United States, 92123
      • Rady Children's Hospital-San Diego ( Site 0347)
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center-Floating Hospital for Children ( Site 0350)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico ( Site 0358)
  • Texas
    • San Antonio, Texas, United States, 78229
      • University Hospital ( Site 0360)
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Children's Hospital of Richmond at VCU ( Site 0359)
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Ruby Memorial Hospital ( Site 0344)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 13 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Exclusion Criteria:

Exclusion Criteria include but are not limited to:

• Is expected to survive less than 72 hours.
• Has a concurrent infection that would interfere with evaluation of response to the study antibacterials (imipenem/cilastatin/relebactam (IMI/REL) or Active Control), including any of the following: endocarditis; osteomyelitis; meningitis; prosthetic joint infection; active pulmonary tuberculosis; disseminated fungal infection; concomitant infection at the time of randomization that requires non-study systemic antibacterial therapy in addition to IV study treatment or oral step-down therapy (medications with only gram-positive activity [e.g., vancomycin, linezolid] are allowed).
• Has HABP/VABP caused by an obstructive process, including lung cancer (or other malignancy metastatic to the lungs resulting in pulmonary obstruction) or other known obstruction.
• Has a cUTI, with any of the following: complete obstruction of any portion of the urinary tract (i.e., requiring a permanent indwelling urinary catheter or instrumentation); documented reflux of ileal loop urinary diversion; suspected or confirmed perinephric or intrarenal abscess; suspected or confirmed prostatitis, urethritis, or epididymitis; trauma to pelvis/urinary tract; presence of indwelling urinary catheter which cannot be removed at study entry.
• Has any of the following medical conditions at screening: history of a seizure disorder (requiring ongoing treatment with anti-convulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years); cystic fibrosis; history of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to IMI, or to any carbapenem, cephalosporin, penicillin, or other β-lactam agent, or to other β-lactamase inhibitors (e.g., tazobactam, sulbactam, clavulanic acid, avibactam).
• Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound study results, or interfere with the participant's participation for the full duration of the study.
• If less than 3 months of age, has received more than 72 hours of empiric antibacterial treatment for suspected meningitis prior to initiation of IV study intervention.

• For all Age Cohorts, provided all other eligibility criteria are met, the following participants may be enrolled:

  • A participant failing prior antibiotic therapy for a current episode of cUTI or HABP/VABP who: Has received the prior antibacterial treatment for at least 48 hours; Has persistent clinical or radiographic findings clearly indicating ongoing infection; Fulfills other laboratory or microbiology criteria for enrollment
  • A participant failing prior antibiotic therapy for a current episode of cIAI who: Has received the prior antibacterial treatment for at least 48 hours; Has persistent clinical or radiographic findings clearly indicating ongoing infection; Fulfills other laboratory or microbiology criteria for enrollment; Has planned operative intervention no more than 24 hours after first dose of study treatment; Has not received any further nonstudy antibiotics postoperatively
• If 3 months of age or older, or <3 months of age without suspected meningitis, has received potentially therapeutic antibacterial therapy (e.g., with gram-negative activity), including bladder infusions with topical urinary antiseptics or antibacterial agents, for a duration of more than 24 hours during the 48 hours preceding the first dose of study intervention.
• Is anticipated to be treated with any of the following medications: valproic acid or divalproex sodium (or has used valproic acid or divalproex sodium in the 2 weeks prior to screening) through 24 hours after completion of the final dose of IV study intervention for participants who receive IMI/REL or carbapenem; concomitant IV, oral, or inhaled antimicrobial agents with gram-negative activity, in addition to those designated in the study intervention groups, during the course of all (IV/oral) study intervention; planned receipt of suppressive/prophylactic antibiotics with gram-negative activity after completion of study intervention.
• Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days prior to screening.
• Has enrolled previously in the current study and been discontinued or has received REL for any other reason.
• Has an estimated creatinine clearance (based on the Cockcroft-Gault equation, for participants ≥12 years of age or estimated glomerular filtration rate (eGFR), based on the modified Schwartz equation, for participants <12 years of age below that specified for the appropriate age range; or requires peritoneal dialysis, hemodialysis, or hemofiltration.
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥5 × upper limit of normal (ULN) at the time of screening. NOTE: Patients with acute hepatic failure or acute decompensation of chronic hepatic failure should also be excluded.
• Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence.
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMI/REL; Participants with cIAI or cUTI will receive imipenem/cilastatin/relebactam (IMI/REL) via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days) up to a maximum of 14 days. Participants with HABP/VABP will receive IMI/REL via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection will receive IMI/REL via IV infusion for 14 days. All oral switch medications will be chosen from a list of acceptable approved agents and will be administered per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines.	Drug: IMI/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.; Other Names: MK-7655A; Drug: Oral 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.
Active Comparator: Active Control; Participants with cIAI or cUTI will receive 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) up to a maximum of 14 days. Participants with HABP/VABP will receive 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 will receive active control via IV infusion for 14 days. All active control and oral switch medications will be administered per authorized PI, SPC, or international treatment guidelines. All active control and oral switch medications will be chosen from a list of acceptable approved agents.	Drug: Active 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.; Drug: Oral 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 28 days
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.	Up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to Day 28
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.	Day 5 up to Day 14
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.	Day 12 up to Day 28
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.	Baseline and Day 19 up to Day 42
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.	Day 5 up to Day 14
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.	Day 12 up to Day 28
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.	Day 19 up to Day 42
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.	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.
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.	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.
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.	At the end of the first infusion on Day 1.
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.	At the end of the first infusion on Day 1.
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.	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.

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2019
• Primary Completion (Actual): May 7, 2024
• Study Completion (Actual): May 7, 2024

Study Registration Dates

• First Submitted: May 28, 2019
• First Submitted That Met QC Criteria: May 28, 2019
• First Posted (Actual): May 31, 2019

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Bacterial Infections; Gram-Negative Bacterial Infections; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; beta-Lactamase Inhibitors; Relebactam
• Other Study ID Numbers: 7655A-021; MK-7655A-021 (Other Identifier: MSD); 2019-000338-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No