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OpenTrials
Completed

NCT Number: NCT02266706

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)

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.

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Key information

Conditions

Proven or Suspected Gram-negative Bacterial Infection Peri-operative Prophylaxis

Age range

7 day–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ceftolozane/Tazobactam 1000/500 mg

Drug

A fixed dose combination (FDC) of 1000 mg ceftolozane and 500 mg tazobactam as a 60 minute infusion.

Ceftolozane/Tazobactam 30/15 mg/kg

Drug

A FDC of 30 mg/kg of ceftolozane and 15 mg/kg of tazobactam as a 60 minute infusion.

Ceftolozane/Tazobactam 20/10 mg/kg

Drug

A FDC of 20 mg/kg of ceftolozane and 10 mg/kg of tazobactam as a 60 minute infusion.

Ceftolozane/Tazobactam 18/9 mg/kg

Drug

A FDC of 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam as a 60 minute infusion.

Ceftolozane/Tazobactam 12/6 mg/kg

Drug

A FDC of 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam as a 60 minute infusion.

Primary outcomes

  1. Maximum Plasma Concentration (Cmax) 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.

    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.

  2. Maximum Plasma Concentration (Cmax) 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.

    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.

  3. Time to Maximum Plasma Concentration (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.

    Blood was collected for the determination of Tmax of ceftolozane.

  4. Time to Maximum Plasma Concentration (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.

    Blood was collected for the determination of Tmax of tazobactam.

  5. Plasma Concentration at the Last Quantifiable Concentration (Clast) 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.

    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.

  6. Plasma Concentration at the Last Quantifiable Concentration (Clast) 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.

    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.

  7. Time of Last Sampling Point (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.

    Blood was collected for the determination of Tlast of ceftolozane.

  8. Time of Last Sampling Point (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.

    Blood was collected for the determination of Tlast of tazobactam.

  9. Area Under the Plasma Concentration-Time Curve (AUClast) 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.

    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.

  10. Area Under the Plasma Concentration-Time Curve (AUClast) 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.

    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.

  11. Area Under the Plasma Concentration-Time Curve (AUC0-inf) 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.

    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.

  12. Area Under the Plasma Concentration-Time Curve (AUC0-inf) 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.

    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.

  13. Elimination Half-life (t1/2) 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.

    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.

  14. Elimination Half-life (t1/2) 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.

    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.

  15. Volume of Distribution at Steady State (Vss) 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.

    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.

  16. Volume of Distribution at Steady State (Vss) 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.

    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.

  17. Plasma Clearance (CL) 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.

    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.

  18. Plasma Clearance (CL) 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.

    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 outcomes

  1. Number of Participants With One or More Adverse Events

    Time frame: Up to Day 10

    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.

  2. Number of Participants Who Discontinued the Study Due to an Adverse Event

    Time frame: Up to Day 10

    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.

Sponsors and collaborators

Lead sponsor

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Oct 17, 2014
Registry last updated
Sep 11, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.