Safety and Pharmacokinetics of Ceftolozane/Tazobactam in Pediatric Participants With Nosocomial Pneumonia (MK-7625A-036)

A Phase 1, Open-label, Non-comparative, Multicenter Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Ceftolozane/Tazobactam (MK-7625A) in Pediatric Participants With Nosocomial Pneumonia

This is a phase 1, open-label, non-comparative, multicenter clinical study to evaluate the safety, tolerability, and pharmacokinetics of ceftolozane/tazobactam (MK-7625A) in pediatric participants with nosocomial pneumonia (NP).

Study Overview

• Status: Completed
• Conditions: Nosocomial Pneumonia
• Intervention / Treatment: Drug: Ceftolozane/Tazobactam

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Chile
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 8380418
      • Hospital Roberto del Río ( Site 1400)
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 0500515
      • Hospital General de Medellin ( Site 1503)
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 08001
      • Ciensalud Ips S A S ( Site 1501)
    • Barranquilla, Atlántico, Colombia, 080020
      • Clinica de la Costa S.A.S. ( Site 1500)
  • Departamento de Córdoba
    • Montería, Departamento de Córdoba, Colombia, 230002
      • Oncomédica S.A.S ( Site 1506)
• Estonia
  • Harju
    • Tallinn, Harju, Estonia, 13419
      • SA Tallinna Lastehaigla/Tallinn Children's Hospital ( Site 0201)
  • Tartu
    • Tartu, Tartu, Estonia, 50406
      • SA Tartu Ulikooli Kliinikum Lastekliinik ( Site 0200)
• Greece
  • Central Macedonia
    • Thessaloniki, Central Macedonia, Greece, 546 42
      • Hippokration General Hospital of Thessaloniki ( Site 0400)
• Mexico
  • Mexico City
    • Mexico City, Mexico City, Mexico, 04530
      • Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 1602)
    • Mexico City, Mexico City, Mexico, 06720
      • Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 1600)
• Russia
  • Moscow
    • Moscow, Moscow, Russia, 119049
      • Morozovskaya Children City Clinical Hospital ( Site 0901)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 194156
      • St. Olga Children City Hospital ( Site 0906)
  • Smolensk Oblast
    • Smolensk, Smolensk Oblast, Russia, 214018
      • Smolensk Regional Clinical Hospital ( Site 0903)
• Spain
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Hospital Universitario Sant Joan de Deu ( Site 1100)
• Ukraine
  • Dnipropetrovsk Oblast
    • Dnipro, Dnipropetrovsk Oblast, Ukraine, 49100
      • SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1205)
  • Ivano-Frankivsk Oblast
    • Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76018
      • Ivano-Frankivsk Regional Children Clinical Hospital ( Site 1204)
  • Kharkivs’ka Oblast’
    • Kharkiv, Kharkivs’ka Oblast’, Ukraine, 61075
      • Kharkiv City Children Hospital 16 ( Site 1200)
  • Kyivska Oblast
    • Kyiv, Kyivska Oblast, Ukraine, 04050
      • Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1203)
• United States
  • Florida
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando ( Site 1318)
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic in Rochester, Minnesota ( Site 1322)
  • New York
    • New York, New York, United States, 10467
      • Montefiore Medical Center [Bronx, NY] ( Site 1313)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Sanford Children's Hospital ( Site 1301)
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University ( Site 1310)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Wisconsin ( Site 1321)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is hospitalized and anticipated to receive a minimum of 8 days of concomitant standard-of-care [SOC] antibiotic therapy for proven or suspected NP.
• If male, is abstinent from heterosexual intercourse, or agrees to use contraception during the intervention period and for ≥30 days after the last dose of study intervention.
• If female, is not pregnant or breastfeeding, or is not a woman of childbearing potential (WOCBP), or is a WOCBP using acceptable contraception, is a WOCBP with negative urine or serum pregnancy test within 48 hours of the first dose of study intervention, or is abstinent from heterosexual intercourse.

Exclusion Criteria:

• Has a documented history of any moderate or severe hypersensitivity (or allergic) reaction to any β-lactam antibacterial.
• Participants 3 months to <18 years of age: has moderate to severe impairment of renal function, defined as an estimated creatinine clearance (CrCL) <50 mL/min/1.73 m2 based on the revised Schwartz equation or requirement for peritoneal dialysis, hemodialysis, or hemofiltration.
• Participants <3 months of age: has CrCL <20 mL/min/1.73 m2 based on the revised Schwartz equation or requirement for peritoneal dialysis, hemodialysis, or hemofiltration.
• Is receiving or is anticipated to receive piperacillin/tazobactam while receiving ceftolozane/tazobactam or has received piperacillin/tazobactam within 24 hours prior to the first dose of ceftolozane/tazobactam.
• Has participated in any clinical study of a therapeutic investigational product within 30 days prior to the first dose of ceftolozane/tazobactam.
• Has previous participation in any study of ceftolozane or ceftolozane/tazobactam.
• Has any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the participant or the quality of study data.
• Has any rapidly progressing disease or immediately life-threatening illness including acute hepatic failure or septic shock.
• Has active immunosuppression.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Ceftolozane/Tazobactam 12 to <18 Years of Age; Participants 12 to <18 years of age with nosocomial pneumonia receive intravenous (IV) ceftolozane/tazobactam every 8 hours for 8-14 days.	Drug: Ceftolozane/Tazobactam; Participants 12 to <18 years of age: IV ceftolozane 2 g with tazobactam 1 g infused over a 60-minute period. Participants <12 years of age: IV ceftolozane 40 mg/kg with tazobactam 20 mg/kg infused over a 60-minute period (not to exceed a dose of ceftolozane 2g and tazobactam 1 g).; Other Names: MK-7625A
Experimental: Group 2: Ceftolozane/Tazobactam 7 to <12 Years of Age; Participants 7 to <12 years of age with nosocomial pneumonia receive IV ceftolozane/tazobactam every 8 hours for 8-14 days.	Drug: Ceftolozane/Tazobactam; Participants 12 to <18 years of age: IV ceftolozane 2 g with tazobactam 1 g infused over a 60-minute period. Participants <12 years of age: IV ceftolozane 40 mg/kg with tazobactam 20 mg/kg infused over a 60-minute period (not to exceed a dose of ceftolozane 2g and tazobactam 1 g).; Other Names: MK-7625A
Experimental: Group 3: Ceftolozane/Tazobactam 2 to <7 Years of Age; Participants 2 to <7 years of age with nosocomial pneumonia receive IV ceftolozane/tazobactam every 8 hours for 8-14 days.	Drug: Ceftolozane/Tazobactam; Participants 12 to <18 years of age: IV ceftolozane 2 g with tazobactam 1 g infused over a 60-minute period. Participants <12 years of age: IV ceftolozane 40 mg/kg with tazobactam 20 mg/kg infused over a 60-minute period (not to exceed a dose of ceftolozane 2g and tazobactam 1 g).; Other Names: MK-7625A
Experimental: Group 4: Ceftolozane/Tazobactam 3 Months to <2 Years of Age; Participants 3 months to <2 years of age with nosocomial pneumonia receive IV ceftolozane/tazobactam every 8 hours for 8-14 days.	Drug: Ceftolozane/Tazobactam; Participants 12 to <18 years of age: IV ceftolozane 2 g with tazobactam 1 g infused over a 60-minute period. Participants <12 years of age: IV ceftolozane 40 mg/kg with tazobactam 20 mg/kg infused over a 60-minute period (not to exceed a dose of ceftolozane 2g and tazobactam 1 g).; Other Names: MK-7625A
Experimental: Group 5: Ceftolozane/Tazobactam Birth to <3 Months of Age; Participants from birth to <3 months of age with nosocomial pneumonia receive IV ceftolozane/tazobactam every 8 hours for 8-14 days.	Drug: Ceftolozane/Tazobactam; Participants 12 to <18 years of age: IV ceftolozane 2 g with tazobactam 1 g infused over a 60-minute period. Participants <12 years of age: IV ceftolozane 40 mg/kg with tazobactam 20 mg/kg infused over a 60-minute period (not to exceed a dose of ceftolozane 2g and tazobactam 1 g).; Other Names: MK-7625A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Any Adverse Events (AEs)	An AE was defined as 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. The percentage of participants experiencing any AE was reported for each arm.	Up to 31 days
Percentage of Participants With Any Serious AEs (SAEs)	An SAE was defined as any untoward medical consequence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other important medical event. The percentage of participants with any SAE was reported for each arm.	Up to 31 days
Percentage of Participants With Any Drug-related AEs	A drug-related AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, and considered related to the study intervention. The percentage of participants with any drug related AEs was reported for each arm.	Up to 31 days
Percentage of Participants With Any Drug-related SAEs	A drug-related SAE was defined any untoward medical consequence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other important medical event, that is considered related to the study intervention. The percentage of participants with any drug related SAEs was reported for each arm.	Up to 31 days
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention	An AE was defined as 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. The percentage of participants with AEs leading to discontinuation of study intervention was reported for each arm.	Up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of Ceftolozane	The plasma concentrations of ceftolozane were determined in each group. Blood samples were collected at pre-specified timepoints to determine the plasma concentrations of ceftolozane in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Area Under the Concentration-time Curve of an 8-hour Dosing Interval (AUC0-8) of Plasma Ceftolozane	AUC0-8 was defined as a measure of ceftolozane exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at pre-specified timepoints to determine the AUC0-8 of ceftolozane in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Maximum Observed Concentration During a Dosage Interval (Cmax) of Plasma Ceftolozane	Cmax was defined as the maximum concentration of ceftolozane observed in plasma. Blood samples were collected at pre-specified timepoints to determine the Cmax of ceftolozane in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Elimination Half-life (t1/2) of Plasma Ceftolozane	Elimination half-life (t1/2) was defined as the time needed to reduce the level of ceftolozane in the blood by one-half (1/2). Blood samples collected at pre-specified timepoints were used to determine the apparent terminal half-life (t1/2) of ceftolozane in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Clearance (CL) of Plasma Ceftolozane	CL was defined as the total clearance of ceftolozane in plasma over time, assessed as the rate at which ceftolozane was removed from the plasma. Blood samples were collected at pre-specified timepoints to determine the CL of ceftolozane in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Volume of Distribution (Vd) of Plasma Ceftolozane	Vd was defined as the distributed volume of study drug in plasma at steady state. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug. Blood samples were collected at pre-specified timepoints to determine the Vd of ceftolozane in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Plasma Concentrations of Tazobactam	The plasma concentrations of tazobactam were determined in each group. Blood samples were collected at pre-specified timepoints to determine the plasma concentrations of tazobactam in participants receiving ceftolozane/tazobactam. No data were calculated for a timepoint if >50% of samples were below limit of quantification (BLOQ).	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Area Under the Concentration-time Curve of an 8-hour Dosing Interval (AUC0-8) of Plasma Tazobactam	AUC0-8 was defined as a measure of tazobactam exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected at pre-specified timepoints to determine the AUC0-8 of tazobactam in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Maximum Observed Concentration During a Dosage Interval (Cmax) of Plasma Tazobactam	Cmax was defined as the maximum concentration of tazobactam observed in plasma. Blood samples were collected at pre-specified timepoints to determine the Cmax of tazobactam in participants receiving ceftolozane/tazobactam. The analysis population consisted of participants who received at least 6 doses of ceftolozane/tazobactam and had at least 1 quantifiable plasma concentration of tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Elimination Half-life (t1/2) of Plasma Tazobactam	Elimination half-life (t1/2) was defined as the time needed to reduce the level of tazobactam in the blood by one-half (1/2). Blood samples collected at pre-specified timepoints were used to determine the apparent terminal half-life (t1/2) of tazobactam in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Clearance (CL) of Plasma Tazobactam	CL was defined as the total clearance of tazobactam in plasma over time, assessed as the rate at which tazobactam was removed from the plasma. Blood samples were collected at pre-specified timepoints to determine the CL of tazobactam in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Volume of Distribution (Vd) of Plasma Tazobactam	Vd is defined as the distributed volume of study drug in plasma at steady state. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug. Blood samples were collected at pre-specified timepoints to determine the Vd of tazobactam in participants receiving ceftolozane/tazobactam.	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion

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): April 17, 2020
• Primary Completion (Actual): September 14, 2024
• Study Completion (Actual): September 14, 2024

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 10, 2020

Study Record Updates

• Last Update Posted (Estimated): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Healthcare-Associated Pneumonia; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Infective Agents, Urinary; beta-Lactamase Inhibitors; ceftolozane, tazobactam drug combination
• Other Study ID Numbers: 7625A-036; MK-7625A-036 (Other Identifier: MSD Protocol Number); 2018-004704-19 (EudraCT Number); 2022-501110-56-00 (Registry Identifier: EU CT); U1111-1279-4959 (Registry Identifier: UTN)

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