Back to resultsPharmacokinetic and Safety Study of Ceftolozane/Tazobactam in Pediatric Participants Receiving Antibiotic Therapy for Proven or Suspected Gram-negative Infection or for Peri-operative Prophylaxis (MK-7625A-010)
Primary Purpose
Proven or Suspected Gram-negative Bacterial Infection, Peri-operative Prophylaxis
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Ceftolozane/Tazobactam 1000/500 mg
Ceftolozane/Tazobactam 30/15 mg/kg
Ceftolozane/Tazobactam 20/10 mg/kg
Ceftolozane/Tazobactam 18/9 mg/kg
Ceftolozane/Tazobactam 12/6 mg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Proven or Suspected Gram-negative Bacterial Infection
Eligibility Criteria
Key Inclusion Criteria:
- Males or non-pregnant females from birth to <18 years of age
- Receiving standard of care antibiotic therapy for suspected or diagnosed Gram-negative infection or for peri-operative prophylaxis
- Groups 1-4: Calculated creatinine clearance rate (CLCR) ≥ 80 ml/min/1.73m2 at baseline
- Group 5: CLCR ≥ 50 ml/min/1.73m2 at baseline
- Group 6: CLCR ≥ 20 ml/min/1.73m2 at baseline
Key Exclusion Criteria:
- Known allergy/hypersensitivity to any β-lactam antibacterial
- History of clinically significant renal, hepatic, or hemodynamic instability
- Planned use of cardiopulmonary bypass or dialysis
- Planned blood transfusion within 24 hours of study drug administration
- Clinically significant abnormal laboratory test results not related to the underlying infection
- Receipt of piperacillin/tazobactam within 24 hours of study drug administration
- Likely to be at risk of hemodynamic disturbance following collection of the required PK blood samples
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1: ≥12 to <18 years TOL/TAZ 1000/500 mg FDC
Cohort 2: ≥7 to <12 years TOL/TAZ 18/9 mg/kg
Cohort 3: ≥2 to <7 years TOL/TAZ 18/9 or 30/15 mg/kg
Cohort 4: ≥3 months to <2 years TOL/TAZ 18/9 or 30/15 mg/kg
Cohort 5: birth to <3 months TOL/TAZ 20/10 mg/kg
Cohort 6: birth to <3 months TOL/TAZ 12/6 or 20/10 mg/kg
Arm Description
Participants ≥12 to <18 years of age received a single dose of ceftolozane/tazobactam (TOL/TAZ) 1000/500 mg FDC as a 60-minute infusion on Day 1.
Participants ≥7 to <12 years of age received a single dose of TOL/TAZ 18/9 mg/kg as a 60-minute infusion on Day 1.
Participants ≥2 to <7 years of age received a single dose of TOL/TAZ 18/9 mg/kg as a 60-minute infusion on Day 1. Participants in this cohort enrolled after interim analysis for Cohort 3 received TOL/TAZ 30/15 mg/kg.
Participants ≥3 months to <2 years of age received a single dose of TOL/TAZ 18/9 mg/kg as a 60-minute infusion on Day 1. Participants in this cohort enrolled after interim analysis for Cohort 3 received TOL/TAZ 30/15 mg/kg.
Participants from birth (>32 weeks gestation, 7 days postnatal) to <3 months of age received a single dose of TOL/TAZ 20/10 mg/kg as a 60-minute infusion on Day 1. After interim analysis for Cohort 4, the original regimen of TOL/TAZ 12/6 mg/kg was changed to TOL/TAZ 20/10.
Participants from birth (≤32 weeks gestation, 7 days postnatal) to <3 months of age with creatinine clearance =20 - 49 mL/min/1.73 m^2 received a single dose of TOL/TAZ 12/6 mg/kg as a 60-minute infusion on Day 1; participants with creatinine clearance ≥50 mL/min/1.73 m^2 received a single dose of TOL/TAZ 20/10 mg/kg as a 60-minute infusion on Day 1. After interim analysis for Cohort 4, the original regimen of TOL/TAZ 12/6 was changed to TOL/TAZ 20/10 mg/kg for participants with creatinine clearance ≥50 mL/min/1.73 m^2.
Outcomes
Primary Outcome Measures
Maximum Plasma Concentration (Cmax) of Ceftolozane
Blood was collected for the determination of Cmax of ceftolozane. Cmax is expressed as geometric least-squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Maximum Plasma Concentration (Cmax) of Tazobactam
Blood was collected for the determination of Cmax of tazobactam. Cmax is expressed as geometric least-squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Time to Maximum Plasma Concentration (Tmax) of Ceftolozane
Blood was collected for the determination of Tmax of ceftolozane.
Time to Maximum Plasma Concentration (Tmax) of Tazobactam
Blood was collected for the determination of Tmax of tazobactam.
Plasma Concentration at the Last Quantifiable Concentration (Clast) of Ceftolozane
Blood was collected for the determination of Clast of ceftolozane. Clast is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Plasma Concentration at the Last Quantifiable Concentration (Clast) of Tazobactam
Blood was collected for the determination of Clast of tazobactam. Clast is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Time of Last Sampling Point (Tlast) of Ceftolozane
Blood was collected for the determination of Tlast of ceftolozane.
Time of Last Sampling Point (Tlast) of Tazobactam
Blood was collected for the determination of Tlast of tazobactam.
Area Under the Plasma Concentration-Time Curve (AUClast) of Ceftolozane
Blood was collected for the determination of AUC from time zero to the last quantifiable concentration of ceftolozane. AUC0-last is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Area Under the Plasma Concentration-Time Curve (AUClast) of Tazobactam
Blood was collected for the determination of AUC from time zero to the last quantifiable concentration of tazobactam. AUC0-last is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Ceftolozane
Blood was collected for the determination of AUC from time zero extrapolated to infinity of ceftolozane. AUC0-inf is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Tazobactam
Blood was collected for the determination of AUC from time zero extrapolated to infinity of tazobactam. AUC0-inf is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Elimination Half-life (t1/2) of Ceftolozane
Blood was collected for the determination of t1/2 of ceftolozane. t1/2 is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Elimination Half-life (t1/2) of Tazobactam
Blood was collected for the determination of t1/2 of tazobactam. t1/2 is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Volume of Distribution at Steady State (Vss) of Ceftolozane
Blood was collected for the determination of Vss of ceftolozane. Vss is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Volume of Distribution at Steady State (Vss) of Tazobactam
Blood was collected for the determination of Vss of tazobactam. Vss is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Plasma Clearance (CL) of Ceftolozane
Blood was collected for the determination of CL of ceftolozane. CL is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Plasma Clearance (CL) of Tazobactam
Blood was collected for the determination of CL of tazobactam. CL is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Secondary Outcome Measures
Number of Participants With One or More Adverse Events
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Number of Participants Who Discontinued the Study Due to an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Full Information
NCT ID
NCT02266706
First Posted
September 22, 2014
Last Updated
August 29, 2019
Sponsor
Cubist Pharmaceuticals LLC
1. Study Identification
Unique Protocol Identification Number
NCT02266706
Brief Title
Pharmacokinetic and Safety Study of Ceftolozane/Tazobactam in Pediatric Participants Receiving Antibiotic Therapy for Proven or Suspected Gram-negative Infection or for Peri-operative Prophylaxis (MK-7625A-010)
Official Title
A Phase 1, Non-comparative, Open-label Study to Characterize the Pharmacokinetics of a Single Intravenous Dose of Ceftolozane/Tazobactam in Pediatric Patients Receiving Standard of Care Antibiotic Therapy for Proven or Suspected Gram-negative Infection or for Peri-operative Prophylaxis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
September 17, 2014 (Actual)
Primary Completion Date
June 8, 2017 (Actual)
Study Completion Date
June 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cubist Pharmaceuticals LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study was to assess the pharmacokinetics, safety, and tolerability of a single intravenous dose of ceftolozane/tazobactam (MK-7625A) in pediatric participants. In each of the 6 age cohorts, an interim analysis of pharmacokinetics (PK) and safety data was conducted after approximately 3 participants had received the initially proposed dose. The interim analysis was to determine whether the initial dose was appropriate based on pre-defined criteria. If data from the interim analysis demonstrated that the initially proposed dose met the above criteria, enrollment was to continue with the same dose administered to approximately 3 additional participants of the same age range. However, if the interim analysis demonstrated that a new optimized dose was required, the new dose was to be administered to approximately 3 additional participants of the same age range.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Proven or Suspected Gram-negative Bacterial Infection, Peri-operative Prophylaxis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: ≥12 to <18 years TOL/TAZ 1000/500 mg FDC
Arm Type
Experimental
Arm Description
Participants ≥12 to <18 years of age received a single dose of ceftolozane/tazobactam (TOL/TAZ) 1000/500 mg FDC as a 60-minute infusion on Day 1.
Arm Title
Cohort 2: ≥7 to <12 years TOL/TAZ 18/9 mg/kg
Arm Type
Experimental
Arm Description
Participants ≥7 to <12 years of age received a single dose of TOL/TAZ 18/9 mg/kg as a 60-minute infusion on Day 1.
Arm Title
Cohort 3: ≥2 to <7 years TOL/TAZ 18/9 or 30/15 mg/kg
Arm Type
Experimental
Arm Description
Participants ≥2 to <7 years of age received a single dose of TOL/TAZ 18/9 mg/kg as a 60-minute infusion on Day 1. Participants in this cohort enrolled after interim analysis for Cohort 3 received TOL/TAZ 30/15 mg/kg.
Arm Title
Cohort 4: ≥3 months to <2 years TOL/TAZ 18/9 or 30/15 mg/kg
Arm Type
Experimental
Arm Description
Participants ≥3 months to <2 years of age received a single dose of TOL/TAZ 18/9 mg/kg as a 60-minute infusion on Day 1. Participants in this cohort enrolled after interim analysis for Cohort 3 received TOL/TAZ 30/15 mg/kg.
Arm Title
Cohort 5: birth to <3 months TOL/TAZ 20/10 mg/kg
Arm Type
Experimental
Arm Description
Participants from birth (>32 weeks gestation, 7 days postnatal) to <3 months of age received a single dose of TOL/TAZ 20/10 mg/kg as a 60-minute infusion on Day 1. After interim analysis for Cohort 4, the original regimen of TOL/TAZ 12/6 mg/kg was changed to TOL/TAZ 20/10.
Arm Title
Cohort 6: birth to <3 months TOL/TAZ 12/6 or 20/10 mg/kg
Arm Type
Experimental
Arm Description
Participants from birth (≤32 weeks gestation, 7 days postnatal) to <3 months of age with creatinine clearance =20 - 49 mL/min/1.73 m^2 received a single dose of TOL/TAZ 12/6 mg/kg as a 60-minute infusion on Day 1; participants with creatinine clearance ≥50 mL/min/1.73 m^2 received a single dose of TOL/TAZ 20/10 mg/kg as a 60-minute infusion on Day 1. After interim analysis for Cohort 4, the original regimen of TOL/TAZ 12/6 was changed to TOL/TAZ 20/10 mg/kg for participants with creatinine clearance ≥50 mL/min/1.73 m^2.
Intervention Type
Drug
Intervention Name(s)
Ceftolozane/Tazobactam 1000/500 mg
Intervention Description
A fixed dose combination (FDC) of 1000 mg ceftolozane and 500 mg tazobactam as a 60 minute infusion.
Intervention Type
Drug
Intervention Name(s)
Ceftolozane/Tazobactam 30/15 mg/kg
Intervention Description
A FDC of 30 mg/kg of ceftolozane and 15 mg/kg of tazobactam as a 60 minute infusion.
Intervention Type
Drug
Intervention Name(s)
Ceftolozane/Tazobactam 20/10 mg/kg
Intervention Description
A FDC of 20 mg/kg of ceftolozane and 10 mg/kg of tazobactam as a 60 minute infusion.
Intervention Type
Drug
Intervention Name(s)
Ceftolozane/Tazobactam 18/9 mg/kg
Intervention Description
A FDC of 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam as a 60 minute infusion.
Intervention Type
Drug
Intervention Name(s)
Ceftolozane/Tazobactam 12/6 mg/kg
Intervention Description
A FDC of 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam as a 60 minute infusion.
Primary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) of Ceftolozane
Description
Blood was collected for the determination of Cmax of ceftolozane. Cmax is expressed as geometric least-squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Maximum Plasma Concentration (Cmax) of Tazobactam
Description
Blood was collected for the determination of Cmax of tazobactam. Cmax is expressed as geometric least-squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Time to Maximum Plasma Concentration (Tmax) of Ceftolozane
Description
Blood was collected for the determination of Tmax of ceftolozane.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Time to Maximum Plasma Concentration (Tmax) of Tazobactam
Description
Blood was collected for the determination of Tmax of tazobactam.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Plasma Concentration at the Last Quantifiable Concentration (Clast) of Ceftolozane
Description
Blood was collected for the determination of Clast of ceftolozane. Clast is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Plasma Concentration at the Last Quantifiable Concentration (Clast) of Tazobactam
Description
Blood was collected for the determination of Clast of tazobactam. Clast is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Time of Last Sampling Point (Tlast) of Ceftolozane
Description
Blood was collected for the determination of Tlast of ceftolozane.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Time of Last Sampling Point (Tlast) of Tazobactam
Description
Blood was collected for the determination of Tlast of tazobactam.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Area Under the Plasma Concentration-Time Curve (AUClast) of Ceftolozane
Description
Blood was collected for the determination of AUC from time zero to the last quantifiable concentration of ceftolozane. AUC0-last is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Area Under the Plasma Concentration-Time Curve (AUClast) of Tazobactam
Description
Blood was collected for the determination of AUC from time zero to the last quantifiable concentration of tazobactam. AUC0-last is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Ceftolozane
Description
Blood was collected for the determination of AUC from time zero extrapolated to infinity of ceftolozane. AUC0-inf is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Tazobactam
Description
Blood was collected for the determination of AUC from time zero extrapolated to infinity of tazobactam. AUC0-inf is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Elimination Half-life (t1/2) of Ceftolozane
Description
Blood was collected for the determination of t1/2 of ceftolozane. t1/2 is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Elimination Half-life (t1/2) of Tazobactam
Description
Blood was collected for the determination of t1/2 of tazobactam. t1/2 is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Volume of Distribution at Steady State (Vss) of Ceftolozane
Description
Blood was collected for the determination of Vss of ceftolozane. Vss is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Volume of Distribution at Steady State (Vss) of Tazobactam
Description
Blood was collected for the determination of Vss of tazobactam. Vss is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Plasma Clearance (CL) of Ceftolozane
Description
Blood was collected for the determination of CL of ceftolozane. CL is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Title
Plasma Clearance (CL) of Tazobactam
Description
Blood was collected for the determination of CL of tazobactam. CL is expressed as geometric mean and percent geometric coefficient of variation, CV% = 100*sqrt(exp(s^2)-1), where s^2 is the observed between-subjects variance on the natural log-scale.
Time Frame
Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.
Secondary Outcome Measure Information:
Title
Number of Participants With One or More Adverse Events
Description
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time Frame
Up to Day 10
Title
Number of Participants Who Discontinued the Study Due to an Adverse Event
Description
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time Frame
Up to Day 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Days
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Males or non-pregnant females from birth to <18 years of age
Receiving standard of care antibiotic therapy for suspected or diagnosed Gram-negative infection or for peri-operative prophylaxis
Groups 1-4: Calculated creatinine clearance rate (CLCR) ≥ 80 ml/min/1.73m2 at baseline
Group 5: CLCR ≥ 50 ml/min/1.73m2 at baseline
Group 6: CLCR ≥ 20 ml/min/1.73m2 at baseline
Key Exclusion Criteria:
Known allergy/hypersensitivity to any β-lactam antibacterial
History of clinically significant renal, hepatic, or hemodynamic instability
Planned use of cardiopulmonary bypass or dialysis
Planned blood transfusion within 24 hours of study drug administration
Clinically significant abnormal laboratory test results not related to the underlying infection
Receipt of piperacillin/tazobactam within 24 hours of study drug administration
Likely to be at risk of hemodynamic disturbance following collection of the required PK blood samples
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
30153232
Citation
Bradley JS, Ang JY, Arrieta AC, Larson KB, Rizk ML, Caro L, Yang S, Yu B, Johnson MG, Rhee EG. Pharmacokinetics and Safety of Single Intravenous Doses of Ceftolozane/Tazobactam in Children With Proven or Suspected Gram-Negative Infection. Pediatr Infect Dis J. 2018 Nov;37(11):1130-1136. doi: 10.1097/INF.0000000000002170.
Results Reference
derived
Learn more about this trial
Pharmacokinetic and Safety Study of Ceftolozane/Tazobactam in Pediatric Participants Receiving Antibiotic Therapy for Proven or Suspected Gram-negative Infection or for Peri-operative Prophylaxis (MK-7625A-010)
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