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

Nosocomial Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04223752
• Other study ID #: 7625A-036
• Secondary ID: MK-7625A-0362022
• Status: Recruiting
• Phase: Phase 1
• Start date: April 17, 2020
• Est. completion date: September 22, 2025

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 22, 2025
• Est. primary completion date: September 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Days to 17 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Healthcare-Associated Pneumonia
• Nosocomial Pneumonia
• Pneumonia

Intervention

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).

Locations

Country	Name	City	State
Chile	Hospital Roberto del Río ( Site 1400)	Santiago	Region M. De Santiago
Colombia	Ciensalud Ips S A S ( Site 1501)	Barranquilla	Atlantico
Colombia	Clinica de la Costa S.A.S. ( Site 1500)	Barranquilla	Atlantico
Colombia	Hospital General de Medellin ( Site 1503)	Medellin	Antioquia
Colombia	Oncomédica S.A.S ( Site 1506)	Montería	Cordoba
Estonia	SA Tallinna Lastehaigla/Tallinn Children's Hospital ( Site 0201)	Tallinn	Harjumaa
Estonia	SA Tartu Ulikooli Kliinikum Lastekliinik ( Site 0200)	Tartu	Tartumaa
Greece	Hippokration General Hospital of Thessaloniki ( Site 0400)	Thessaloniki	Kentriki Makedonia
Mexico	Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 1600)	Mexico City	Distrito Federal
Mexico	Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 1602)	Mexico City	Distrito Federal
Russian Federation	Morozovskaya Children City Clinical Hospital ( Site 0901)	Moscow	Moskva
Russian Federation	St. Olga Children City Hospital ( Site 0906)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	Smolensk Regional Clinical Hospital ( Site 0903)	Smolensk	Smolenskaya Oblast
Spain	Hospital Universitario Sant Joan de Deu ( Site 1100)	Esplugues de Llobregat	Barcelona
Ukraine	SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1205)	Dnipro	Dnipropetrovska Oblast
Ukraine	Ivano-Frankivsk Regional Children Clinical Hospital ( Site 1204)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Kharkiv City Children Hospital 16 ( Site 1200)	Kharkiv	Kharkivska Oblast
Ukraine	Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1203)	Kyiv	Kyivska Oblast
United States	Children's Wisconsin ( Site 1321)	Milwaukee	Wisconsin
United States	West Virginia University ( Site 1310)	Morgantown	West Virginia
United States	Montefiore Medical Center [Bronx, NY] ( Site 1313)	New York	New York
United States	AdventHealth Orlando ( Site 1318)	Orlando	Florida
United States	Sanford Children's Hospital ( Site 1301)	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Chile,  Colombia,  Estonia,  Greece,  Mexico,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary