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).
Brief Title
Safety and Pharmacokinetics of Ceftolozane/Tazobactam in Pediatric Participants With Nosocomial Pneumonia (MK-7625A-036)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Nosocomial Pneumonia
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
7 Days
NCT Id
NCT04223752
Org Class
Industry
Org Full Name
Merck Sharp & Dohme LLC
Org Study Id
7625A-036
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Participants With Any Adverse Events (AEs)
Outcome Time Frame
Up to 31 days
Outcome Description
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.
Outcome Measure
Percentage of Participants With Any Serious AEs (SAEs)
Outcome Time Frame
Up to 31 days
Outcome Description
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.
Outcome Measure
Percentage of Participants With Any Drug-related AEs
Outcome Time Frame
Up to 31 days
Outcome Description
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.
Outcome Measure
Percentage of Participants With Any Drug-related SAEs
Outcome Time Frame
Up to 31 days
Outcome Description
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.
Outcome Measure
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention
Outcome Time Frame
Up to 14 days
Secondary Ids
Secondary Id
MK-7625A-036
Secondary Id
2022-501110-56-00
Secondary Id
U1111-1279-4959
Secondary Id
2018-004704-19
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Plasma Concentrations of Ceftolozane
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Area Under the Concentration-time Curve of an 8-hour Dosing Interval (AUC0-8) of Plasma Ceftolozane
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Maximum Observed Concentration During a Dosage Interval (Cmax) of Plasma Ceftolozane
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Elimination Half-life (t1/2) of Plasma Ceftolozane
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Clearance (CL) of Plasma Ceftolozane
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Volume of Distribution (Vd) of Plasma Ceftolozane
Outcome Description
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).
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Plasma Concentrations of Tazobactam
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Area Under the Concentration-time Curve of an 8-hour Dosing Interval (AUC0-8) of Plasma Tazobactam
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Maximum Observed Concentration During a Dosage Interval (Cmax) of Plasma Tazobactam
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Elimination Half-life (t1/2) of Plasma Tazobactam
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Clearance (CL) of Plasma Tazobactam
Outcome Description
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.
Outcome Time Frame
Day 3: 1, between 4-5, and between 7-8 hours post start of infusion
Outcome Measure
Volume of Distribution (Vd) of Plasma Tazobactam
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Michelle Collins-Ogle
Investigator Email
mogle@montefiore.org
Investigator Phone
919-451-0413
Categories Mesh Debug
Lung --- HEALTHCARE-ASSOCIATED PNEUMONIA
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
COVID-19 --- PNEUMONIA
Lung --- PNEUMONIA
COVID-19 --- RESPIRATORY TRACT INFECTIONS
Lung --- RESPIRATORY TRACT INFECTIONS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
HEALTHCARE-ASSOCIATED PNEUMONIA
CROSS INFECTION
INFECTIONS
PNEUMONIA
RESPIRATORY TRACT INFECTIONS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
IATROGENIC DISEASE
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
CEFTOLOZANE, TAZOBACTAM DRUG COMBINATION