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: Recruiting
• Conditions: Nosocomial Pneumonia
• Intervention / Treatment: Drug: Ceftolozane/Tazobactam

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Chile
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 8380418
      • Recruiting
      • Hospital Roberto del Río ( Site 1400)
      • Contact: Study Coordinator; Phone Number: 992360000
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 0500515
      • Recruiting
      • Hospital General de Medellin ( Site 1503)
      • Contact: Study Coordinator; Phone Number: 5743847300
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 08001
      • Recruiting
      • Ciensalud Ips S A S ( Site 1501)
      • Contact: Study Coordinator; Phone Number: 57 3183894721
    • Barranquilla, Atlantico, Colombia, 080020
      • Recruiting
      • Clinica de la Costa S.A.S. ( Site 1500)
      • Contact: Study Coordinator; Phone Number: 3116438539
  • Cordoba
    • Montería, Cordoba, Colombia, 230002
      • Recruiting
      • Oncomédica S.A.S ( Site 1506)
      • Contact: Study Coordinator; Phone Number: +57 (604) 7862333
• Estonia
  • Harjumaa
    • Tallinn, Harjumaa, Estonia, 13419
      • Recruiting
      • SA Tallinna Lastehaigla/Tallinn Children's Hospital ( Site 0201)
      • Contact: Study Coordinator; Phone Number: +3726977122
  • Tartumaa
    • Tartu, Tartumaa, Estonia, 50406
      • Recruiting
      • SA Tartu Ulikooli Kliinikum Lastekliinik ( Site 0200)
      • Contact: Study Coordinator; Phone Number: +3727319550
• Greece
  • Kentriki Makedonia
    • Thessaloniki, Kentriki Makedonia, Greece, 546 42
      • Recruiting
      • Hippokration General Hospital of Thessaloniki ( Site 0400)
      • Contact: Study Coordinator; Phone Number: +306937442644
• Mexico
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 04530
      • Recruiting
      • Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 1602)
      • Contact: Study Coordinator; Phone Number: 5525600809
    • Mexico City, Distrito Federal, Mexico, 06720
      • Recruiting
      • Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 1600)
      • Contact: Study Coordinator; Phone Number: 525539391946
• Russian Federation
  • Moskva
    • Moscow, Moskva, Russian Federation, 119049
      • Completed
      • Morozovskaya Children City Clinical Hospital ( Site 0901)
  • Sankt-Peterburg
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 194156
      • Completed
      • St. Olga Children City Hospital ( Site 0906)
  • Smolenskaya Oblast
    • Smolensk, Smolenskaya Oblast, Russian Federation, 214018
      • Completed
      • Smolensk Regional Clinical Hospital ( Site 0903)
• Spain
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Recruiting
      • Hospital Universitario Sant Joan de Deu ( Site 1100)
      • Contact: Study Coordinator; Phone Number: +34932532100
• Ukraine
  • Dnipropetrovska Oblast
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49100
      • Recruiting
      • SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1205)
      • Contact: Study Coordinator; Phone Number: +380509142649
  • Ivano-Frankivska Oblast
    • Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine, 76018
      • Recruiting
      • Ivano-Frankivsk Regional Children Clinical Hospital ( Site 1204)
      • Contact: Study Coordinator; Phone Number: +380681040592
  • Kharkivska Oblast
    • Kharkiv, Kharkivska Oblast, Ukraine, 61075
      • Suspended
      • Kharkiv City Children Hospital 16 ( Site 1200)
  • Kyivska Oblast
    • Kyiv, Kyivska Oblast, Ukraine, 04050
      • Completed
      • Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1203)
• United States
  • Florida
    • Orlando, Florida, United States, 32803
      • Recruiting
      • AdventHealth Orlando ( Site 1318)
      • Contact: Study Coordinator; Phone Number: 407-821-3691
  • New York
    • New York, New York, United States, 10467
      • Completed
      • Montefiore Medical Center [Bronx, NY] ( Site 1313)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Completed
      • Sanford Children's Hospital ( Site 1301)
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Completed
      • West Virginia University ( Site 1310)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Children's Wisconsin ( Site 1321)
      • Contact: Study Coordinator; Phone Number: 414-337-7070

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 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.	Up to 31 days
Percentage of participants with any serious AEs (SAEs)	An SAE is 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.	Up to 31 days
Percentage of participants with any drug-related AEs	A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, and considered related to the study intervention.	Up to 31 days
Percentage of participants with any drug-related SAEs	A drug-related SAE is 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.	Up to 31 days
Percentage of participants with AEs leading to discontinuation of study intervention	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.	Up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of ceftolozane	The plasma concentrations of ceftolozane will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Area under the concentration-time curve of an 8-hour dosing interval (AUC0-8) of plasma ceftolozane	The plasma AUC0-8 of ceftolozane will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Area under the concentration-time curve of an 8-hour dosing interval (AUC0-8) of plasma tazobactam	The plasma AUC0-8 of tazobactam will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Maximum observed concentration during a dosage interval (Cmax) of plasma ceftolozane	The plasma Cmax of ceftolozane will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Maximum observed concentration during a dosage interval (Cmax) of plasma tazobactam	The plasma Cmax of tazobactam will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Elimination half-life (t1/2) of plasma ceftolozane	The plasma t1/2 of ceftolozane will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Elimination half-life (t1/2) of plasma tazobactam	The plasma t1/2 of tazobactam will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Volume of distribution (Vd) of plasma ceftolozane	The plasma Vd of ceftolozane will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Volume of distribution (Vd) of plasma tazobactam	The plasma Vd of tazobactam will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Clearance (CL) of plasma ceftolozane	The plasma CL of ceftolozane will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after start of infusion
Clearance (CL) of plasma tazobactam	The plasma CL of tazobactam will be determined in each group.	Day 3: 1, between 4-5, and between 7-8 hours after 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 (Estimated): September 22, 2025
• Study Completion (Estimated): September 22, 2025

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 (Actual): June 13, 2024
• Last Update Submitted That Met QC Criteria: June 12, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

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

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/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