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)

ID: NCT02266706
Status: Completed
Phase: Phase 1
Start Date: September 17, 2014
First Submitted: September 22, 2014
Last Updated: July 28, 2017
Results: N/A
Sponsors & Collaborators: Cubist Pharmaceuticals LLC
Location: N/A
Conditions: Proven or Suspected Gram-negative Bacterial Infection, Peri-operative Prophylaxis
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Study Description

Brief Summary

The purpose of this study is to assess the pharmacokinetics, safety, and tolerability of a single intravenous dose of ceftolozane/tazobactam in pediatric participants.

Ceftolozane/tazobactam is a novel antibacterial consisting of ceftolozane, a unique antipseudomonal cephalosporin, with tazobactam, a well-established β-lactamase inhibitor.

This is the first study investigating the use of ceftolozane/tazobactam in pediatric participants.

Detailed Description

Screening assessments will occur within 48 hours of study drug administration (Day 1). Baseline assessments will be performed following eligibility verification based on screening assessments.

Participants will be monitored for safety 24 hours post study drug infusion. The site will contact the participant and/or parent (or appropriate legal representative) via telephone at Study Day 8 (± 2 days) for assessment of adverse events and concomitant medications and procedures.

In each age cohort, an interim analysis of PK and safety data will be conducted after 3 participants have received the initially proposed dose. The interim analysis will determine whether this initial dose was appropriate based on pre-defined criteria.

If data from the interim analysis demonstrates that the initially proposed dose meets the criteria above, enrollment will continue with the same dose administered to 3 additional participants. However, if the interim analysis demonstrates that a new optimized adjusted dose is required, the new adjusted dose will be administered to 3 new participants of the same age range. In subsequent cohorts, the initial dose is also subject to change based upon the results of the interim analysis in previous cohorts.
Condition or disease Intervention/treatment Phase

Peri-operative Prophylaxis

Proven or Suspected Gram-negative Bacterial Infection

Drug: Ceftolozane/Tazobactam 1.5 g
Other Names
Drug: Ceftolozane/Tazobactam 27 mg/kg
Other Names
Drug: Ceftolozane/Tazobactam 18 mg/kg
Other Names
Phase 1

Tracking Information

First Submitted DateSeptember 22, 2014
Last Update Posted DateJuly 28, 2017
Actual Start DateSeptember 17, 2014
Actual Completion DateJune 15, 2017
Actual Primary Completion DateJune 08, 2017
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Plasma clearance (CL) of ceftolozane/tazobactam [Time Frame: Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.]

  • Volume of distribution at steady state (Vss) of ceftolozane/tazobactam [Time Frame: Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.]

  • Elimination half-life (t1/2) of ceftolozane/tazobactam [Time Frame: Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.]

  • Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) of ceftolozane/tazobactam [Time Frame: Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.]

  • Area under the plasma concentration-time curve from 0 to time of last sample collected (AUC0-tlast) of ceftolozane/tazobactam [Time Frame: Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.]

  • Time of last sampling point (Tlast) of ceftolozane/tazobactam [Time Frame: Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.]

  • Concentration at last sampling point (Clast) of ceftolozane/tazobactam [Time Frame: Assessed at 0, 0.5, 1, 2, 4, and 6 hours after the start of study drug administration.]

  • Time to Cmax (Tmax) of ceftolozane/tazobactam [Time Frame: Assessed up to 6 hours after the start of study drug administration.]

  • Maximum plasma concentration (Cmax) of ceftolozane/tazobactam [Time Frame: Assessed up to 6 hours after the start of study drug administration.]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Number of participants with one or more Adverse Events [Time Frame: Participants will be followed from the time of study drug administration (study day 1) through the last study follow up (may occur up to study day 10).]

  • Number of participants who discontinued study due to an Adverse Event [Time Frame: Participants will be followed on the day of study drug administration (study day 1).]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitlePharmacokinetic 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 TitleA 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
Brief Summary

The purpose of this study is to assess the pharmacokinetics, safety, and tolerability of a single intravenous dose of ceftolozane/tazobactam in pediatric participants.

Ceftolozane/tazobactam is a novel antibacterial consisting of ceftolozane, a unique antipseudomonal cephalosporin, with tazobactam, a well-established β-lactamase inhibitor.

This is the first study investigating the use of ceftolozane/tazobactam in pediatric participants.

Detailed Description

Screening assessments will occur within 48 hours of study drug administration (Day 1). Baseline assessments will be performed following eligibility verification based on screening assessments.

Participants will be monitored for safety 24 hours post study drug infusion. The site will contact the participant and/or parent (or appropriate legal representative) via telephone at Study Day 8 (± 2 days) for assessment of adverse events and concomitant medications and procedures.

In each age cohort, an interim analysis of PK and safety data will be conducted after 3 participants have received the initially proposed dose. The interim analysis will determine whether this initial dose was appropriate based on pre-defined criteria.

If data from the interim analysis demonstrates that the initially proposed dose meets the criteria above, enrollment will continue with the same dose administered to 3 additional participants. However, if the interim analysis demonstrates that a new optimized adjusted dose is required, the new adjusted dose will be administered to 3 new participants of the same age range. In subsequent cohorts, the initial dose is also subject to change based upon the results of the interim analysis in previous cohorts.

Study TypeInterventional
Study PhasePhase 1
Estimated Enrollment
37
Allocation
Non-Randomized
Interventional Model
Parallel Assignment
Masking
None
Primary Purpose
Treatment
Conditions
Peri-operative Prophylaxis
Proven or Suspected Gram-negative Bacterial Infection
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Ceftolozane/Tazobactam 1.5 g

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

Other Names
Drug: Ceftolozane/Tazobactam 27 mg/kg

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

Other Names
Drug: Ceftolozane/Tazobactam 18 mg/kg

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

Other Names
Study Groups/Cohorts
Group 1: 12 to less than 18 years old
Includes ages 12 years up to, but not including, 18 years. Six participants to receive a fixed dose of ceftolozane/tazobactam (comprising 1000 mg ceftolozane and 500 mg tazobactam) as a 60 minute infusion.

Group 2: 7 to less than 12 years old
Includes ages 7 years up to, but not including, 12 years. Six participants to receive a dose of ceftolozane/tazobactam (comprising 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam) as a 60 minute infusion.

Group 3: 2 to less than 7 years old
Includes ages 2 years up to, but not including, 7 years. Six participants to receive a dose of ceftolozane/tazobactam (comprising 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam) as a 60 minute infusion.

Group 4: 3 months to less than 2 years
Includes ages 3 months up to, but not including, 2 years. Six participants to receive a dose of ceftolozane/tazobactam (comprising 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam) as a 60 minute infusion.

Group 5: less than 3 months; greater than 32 weeks gestation
Includes ages birth (7 days postnatal) up to, but not including, 3 months and greater than 32 weeks gestation. Six participants to receive a dose of ceftolozane/tazobactam (comprising 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam) as a 60 minute infusion.

Group 6: less than 3 months and 32 weeks gestation or less
Includes ages birth (7 days postnatal) up to, but not including, 3 months and less than or equal to 32 weeks gestation. Six participants to receive a dose of ceftolozane/tazobactam (comprising 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam) as a 60 minute infusion.

Study Arms
Experimental Group 1: 12 to less than 18 years old
Includes ages 12 years up to, but not including, 18 years. Six participants to receive a fixed dose of ceftolozane/tazobactam (comprising 1000 mg ceftolozane and 500 mg tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 1.5 g
1.5 g fixed dose combination (FDC) of 1000 mg ceftolozane and 500 mg tazobactam as a 60 minute infusion.

Experimental Group 2: 7 to less than 12 years old
Includes ages 7 years up to, but not including, 12 years. Six participants to receive a dose of ceftolozane/tazobactam (comprising 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 27 mg/kg
A FDC of 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam as a 60 minute infusion.

Experimental Group 3: 2 to less than 7 years old
Includes ages 2 years up to, but not including, 7 years. Six participants to receive a dose of ceftolozane/tazobactam (comprising 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 27 mg/kg
A FDC of 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam as a 60 minute infusion.

Experimental Group 4: 3 months to less than 2 years
Includes ages 3 months up to, but not including, 2 years. Six participants to receive a dose of ceftolozane/tazobactam (comprising 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 27 mg/kg
A FDC of 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam as a 60 minute infusion.

Experimental Group 5: less than 3 months; greater than 32 weeks gestation
Includes ages birth (7 days postnatal) up to, but not including, 3 months and greater than 32 weeks gestation. Six participants to receive a dose of ceftolozane/tazobactam (comprising 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 18 mg/kg
A FDC of 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam as a 60 minute infusion.

Experimental Group 6: less than 3 months and 32 weeks gestation or less
Includes ages birth (7 days postnatal) up to, but not including, 3 months and less than or equal to 32 weeks gestation. Six participants to receive a dose of ceftolozane/tazobactam (comprising 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 18 mg/kg
A FDC of 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam as a 60 minute infusion.

Arm Intervention/Treatment
Experimental Group 1: 12 to less than 18 years old
Includes ages 12 years up to, but not including, 18 years. Six participants to receive a fixed dose of ceftolozane/tazobactam (comprising 1000 mg ceftolozane and 500 mg tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 1.5 g
Experimental Group 2: 7 to less than 12 years old
Includes ages 7 years up to, but not including, 12 years. Six participants to receive a dose of ceftolozane/tazobactam (comprising 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 27 mg/kg
Experimental Group 3: 2 to less than 7 years old
Includes ages 2 years up to, but not including, 7 years. Six participants to receive a dose of ceftolozane/tazobactam (comprising 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 27 mg/kg
Experimental Group 4: 3 months to less than 2 years
Includes ages 3 months up to, but not including, 2 years. Six participants to receive a dose of ceftolozane/tazobactam (comprising 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 27 mg/kg
Experimental Group 5: less than 3 months; greater than 32 weeks gestation
Includes ages birth (7 days postnatal) up to, but not including, 3 months and greater than 32 weeks gestation. Six participants to receive a dose of ceftolozane/tazobactam (comprising 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 18 mg/kg
Experimental Group 6: less than 3 months and 32 weeks gestation or less
Includes ages birth (7 days postnatal) up to, but not including, 3 months and less than or equal to 32 weeks gestation. Six participants to receive a dose of ceftolozane/tazobactam (comprising 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam) as a 60 minute infusion.
Drug : Ceftolozane/Tazobactam 18 mg/kg

Recruitment Information

Recruitment Status:Completed
Enrollment37
Completion DateJune 15, 2017
Eligibility Criteria: Key Inclusion Criteria:
1. Males or non-pregnant females from birth to <18 years of age
2. Receiving standard of care antibiotic therapy for suspected or diagnosed Gram-negative infection or for peri-operative prophylaxis
3. Groups 1-4: Calculated creatinine clearance rate (CLCR) ≥ 80 ml/min/1.73m2 at baseline
4. Group 5: CLCR ≥ 50 ml/min/1.73m2 at baseline
5. Group 6: CLCR ≥ 20 ml/min/1.73m2 at baseline
Key
Exclusion Criteria:
1. Known allergy/hypersensitivity to any β-lactam antibacterial
2. History of clinically significant renal, hepatic, or hemodynamic instability
3. Planned use of cardiopulmonary bypass or dialysis
4. Planned blood transfusion within 24 hours of study drug administration
5. Clinically significant abnormal laboratory test results not related to the underlying infection
6. Receipt of piperacillin/tazobactam within 24 hours of study drug administration
7. Likely to be at risk of hemodynamic disturbance following collection of the required PK blood samples
GenderAll
Age N/A to 17 Years
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
United States

Administrative Information

NCT Number:NCT02266706
Other Study ID Numbers
7625A-010
CXA-PEDS-13-08
NCT02725216
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Cubist Pharmaceuticals LLC
Collaborators
Not Available
Investigators
Study Director
Medical Director
Merck Sharp & Dohme Corp.