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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04223752

Enrollment

Registered

2020-01-10

Start date

2020-04-17

Completion date

2024-09-14

Last updated

2025-09-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nosocomial Pneumonia

Brief 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).

Interventions

DRUGCeftolozane/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).

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

7 Days to 17 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Any Adverse Events (AEs)	Up to 31 days	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.
Percentage of Participants With Any Serious AEs (SAEs)	Up to 31 days	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.
Percentage of Participants With Any Drug-related AEs	Up to 31 days	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.
Percentage of Participants With Any Drug-related SAEs	Up to 31 days	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.
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention	Up to 14 days	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.

Secondary

Measure	Time frame	Description
Volume of Distribution (Vd) of Plasma Ceftolozane	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Plasma Concentrations of Tazobactam	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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).
Area Under the Concentration-time Curve of an 8-hour Dosing Interval (AUC0-8) of Plasma Tazobactam	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Plasma Concentrations of Ceftolozane	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Elimination Half-life (t1/2) of Plasma Tazobactam	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Clearance (CL) of Plasma Tazobactam	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Volume of Distribution (Vd) of Plasma Tazobactam	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Maximum Observed Concentration During a Dosage Interval (Cmax) of Plasma Tazobactam	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Area Under the Concentration-time Curve of an 8-hour Dosing Interval (AUC0-8) of Plasma Ceftolozane	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Maximum Observed Concentration During a Dosage Interval (Cmax) of Plasma Ceftolozane	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Elimination Half-life (t1/2) of Plasma Ceftolozane	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.
Clearance (CL) of Plasma Ceftolozane	Day 3: 1, between 4-5, and between 7-8 hours post start of infusion	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.

Countries

Chile, Colombia, Estonia, Greece, Mexico, Russia, Spain, Ukraine, United States

Participant flow

Pre-assignment details

One participant was enrolled in error in the Group 5 arm and was excluded from the All participants as treated (APaT) population; the participant did not receive study intervention.

Participants by arm

Arm	Count
Group 1: Ceftolozane/Tazobactam 12 to <18 Years of Age Participants 12 to \<18 years of age with nosocomial pneumonia received intravenous (IV) ceftolozane 2g and tazobactam 1g every 8 hours for 8-14 days.	8
Group 2: Ceftolozane/Tazobactam 7 to <12 Years of Age Participants 7 to \<12 years of age with nosocomial pneumonia received IV ceftolozane 40 mg/kg and tazobactam 20 mg/kg every 8 hours for 8-14 days.	7
Group 3: Ceftolozane/Tazobactam 2 to <7 Years of Age Participants 2 to \<7 years of age with nosocomial pneumonia received IV ceftolozane 40 mg/kg and tazobactam 20 mg/kg every 8 hours for 8-14 days.	8
Group 4: Ceftolozane/Tazobactam 3 Months to <2 Years of Age Participants 3 months to \<2 years of age with nosocomial pneumonia received IV ceftolozane 40 mg/kg and tazobactam 20 mg/kg every 8 hours for 8-14 days.	10
Group 5: Ceftolozane/Tazobactam Birth to <3 Months of Age Participants from birth to \<3 months of age with nosocomial pneumonia received IV ceftolozane 40 mg/kg and 20 mg/kg tazobactam every 8 hours for 8-14 days.	8
Total	41

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Death	0	0	0	2	1
Overall Study	Participant enrolled in error	0	0	0	0	1

Baseline characteristics

Characteristic	Group 1: Ceftolozane/Tazobactam 12 to <18 Years of Age	Group 2: Ceftolozane/Tazobactam 7 to <12 Years of Age	Group 3: Ceftolozane/Tazobactam 2 to <7 Years of Age	Group 4: Ceftolozane/Tazobactam 3 Months to <2 Years of Age	Group 5: Ceftolozane/Tazobactam Birth to <3 Months of Age	Total
Age, Continuous	14.345 Years STANDARD_DEVIATION 1.6408	9.709 Years STANDARD_DEVIATION 1.91	3.185 Years STANDARD_DEVIATION 0.743	0.806 Years STANDARD_DEVIATION 0.2994	0.102 Years STANDARD_DEVIATION 0.0628	5.294 Years STANDARD_DEVIATION 5.6787
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	5 Participants	3 Participants	3 Participants	3 Participants	15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants	2 Participants	5 Participants	7 Participants	5 Participants	26 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants	3 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	2 Participants
Race (NIH/OMB) More than one race	1 Participants	2 Participants	1 Participants	0 Participants	2 Participants	6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	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
Race (NIH/OMB) White	7 Participants	4 Participants	7 Participants	7 Participants	5 Participants	30 Participants
Sex: Female, Male Female	6 Participants	2 Participants	6 Participants	2 Participants	3 Participants	19 Participants
Sex: Female, Male Male	2 Participants	5 Participants	2 Participants	8 Participants	5 Participants	22 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
deaths Total, all-cause mortality	0 / 8	0 / 7	0 / 8	2 / 10	1 / 8
other Total, other adverse events	4 / 8	5 / 7	6 / 8	9 / 10	6 / 7
serious Total, serious adverse events	1 / 8	2 / 7	0 / 8	3 / 10	2 / 7

Outcome results

Primary

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.

Time frame: Up to 14 days

Population: The analysis population consisted of participants who received any dose (including partial doses) of ceftolozane/tazobactam.

Arm	Measure	Value (NUMBER)	Dispersion
Group 1: Ceftolozane/Tazobactam 12 to <18 Years of Age	Percentage of Participants With AEs Leading to Discontinuation of Study Intervention	0.0 Percentage of participants	95% Confidence Interval 0
Group 2: Ceftolozane/Tazobactam 7 to <12 Years of Age	Percentage of Participants With AEs Leading to Discontinuation of Study Intervention	0.0 Percentage of participants	95% Confidence Interval 0
Group 3: Ceftolozane/Tazobactam 2 to <7 Years of Age	Percentage of Participants With AEs Leading to Discontinuation of Study Intervention	0.0 Percentage of participants	95% Confidence Interval 0
Group 4: Ceftolozane/Tazobactam 3 Months to <2 Years of Age	Percentage of Participants With AEs Leading to Discontinuation of Study Intervention	0.0 Percentage of participants	95% Confidence Interval 0
Group 5: Ceftolozane/Tazobactam Birth to <3 Months of Age	Percentage of Participants With AEs Leading to Discontinuation of Study Intervention	0.0 Percentage of participants	95% Confidence Interval 0

Primary

Percentage of Participants With Any Adverse Events (AEs)

Time frame: Up to 31 days

Population: The analysis population consisted of participants who received any dose (including partial doses) of ceftolozane/tazobactam.

Arm	Measure	Value (NUMBER)	Dispersion
Group 1: Ceftolozane/Tazobactam 12 to <18 Years of Age	Percentage of Participants With Any Adverse Events (AEs)	50.0 Percentage of participants	95% Confidence Interval 15.7
Group 2: Ceftolozane/Tazobactam 7 to <12 Years of Age	Percentage of Participants With Any Adverse Events (AEs)	71.4 Percentage of participants	95% Confidence Interval 29
Group 3: Ceftolozane/Tazobactam 2 to <7 Years of Age	Percentage of Participants With Any Adverse Events (AEs)	75.0 Percentage of participants	95% Confidence Interval 34.9
Group 4: Ceftolozane/Tazobactam 3 Months to <2 Years of Age	Percentage of Participants With Any Adverse Events (AEs)	90.0 Percentage of participants	95% Confidence Interval 55.5
Group 5: Ceftolozane/Tazobactam Birth to <3 Months of Age	Percentage of Participants With Any Adverse Events (AEs)	85.7 Percentage of participants	95% Confidence Interval 42.1

Primary

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.

Time frame: Up to 31 days

Population: The analysis population consisted of participants who received any dose (including partial doses) of ceftolozane/tazobactam.

Arm	Measure	Value (NUMBER)	Dispersion
Group 1: Ceftolozane/Tazobactam 12 to <18 Years of Age	Percentage of Participants With Any Drug-related AEs	0.0 Percentage of participants	95% Confidence Interval 0
Group 2: Ceftolozane/Tazobactam 7 to <12 Years of Age	Percentage of Participants With Any Drug-related AEs	0.0 Percentage of participants	95% Confidence Interval 0
Group 3: Ceftolozane/Tazobactam 2 to <7 Years of Age	Percentage of Participants With Any Drug-related AEs	0.0 Percentage of participants	95% Confidence Interval 0
Group 4: Ceftolozane/Tazobactam 3 Months to <2 Years of Age	Percentage of Participants With Any Drug-related AEs	0.0 Percentage of participants	95% Confidence Interval 0
Group 5: Ceftolozane/Tazobactam Birth to <3 Months of Age	Percentage of Participants With Any Drug-related AEs	14.3 Percentage of participants	95% Confidence Interval 0.4

Primary

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.

Time frame: Up to 31 days

Population: The analysis population consisted of participants who received any dose (including partial doses) of ceftolozane/tazobactam.

Arm	Measure	Value (NUMBER)	Dispersion
Group 1: Ceftolozane/Tazobactam 12 to <18 Years of Age	Percentage of Participants With Any Drug-related SAEs	0.0 Percentage of participants	95% Confidence Interval 0
Group 2: Ceftolozane/Tazobactam 7 to <12 Years of Age	Percentage of Participants With Any Drug-related SAEs	0.0 Percentage of participants	95% Confidence Interval 0
Group 3: Ceftolozane/Tazobactam 2 to <7 Years of Age	Percentage of Participants With Any Drug-related SAEs	0.0 Percentage of participants	95% Confidence Interval 0
Group 4: Ceftolozane/Tazobactam 3 Months to <2 Years of Age	Percentage of Participants With Any Drug-related SAEs	0.0 Percentage of participants	95% Confidence Interval 0
Group 5: Ceftolozane/Tazobactam Birth to <3 Months of Age	Percentage of Participants With Any Drug-related SAEs	0.0 Percentage of participants	95% Confidence Interval 0

Primary

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.

Time frame: Up to 31 days

Population: The analysis population consisted of participants who received any dose (including partial doses) of ceftolozane/tazobactam.

Arm	Measure	Value (NUMBER)	Dispersion
Group 1: Ceftolozane/Tazobactam 12 to <18 Years of Age	Percentage of Participants With Any Serious AEs (SAEs)	12.5 Percentage of participants	95% Confidence Interval 0.3
Group 2: Ceftolozane/Tazobactam 7 to <12 Years of Age	Percentage of Participants With Any Serious AEs (SAEs)	28.6 Percentage of participants	95% Confidence Interval 3.7
Group 3: Ceftolozane/Tazobactam 2 to <7 Years of Age	Percentage of Participants With Any Serious AEs (SAEs)	0.0 Percentage of participants	95% Confidence Interval 0
Group 4: Ceftolozane/Tazobactam 3 Months to <2 Years of Age	Percentage of Participants With Any Serious AEs (SAEs)	30.0 Percentage of participants	95% Confidence Interval 6.7
Group 5: Ceftolozane/Tazobactam Birth to <3 Months of Age	Percentage of Participants With Any Serious AEs (SAEs)	28.6 Percentage of participants	95% Confidence Interval 3.7

Secondary

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.