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)

NCT ID: NCT02266706

Last Updated: 2019-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-17
• Study Completion Date: 2017-06-15

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: ≥12 to <18 years TOL/TAZ 1000/500 mg FDC

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.

Group Type: EXPERIMENTAL

Ceftolozane/Tazobactam 1000/500 mg

Intervention Type: DRUG

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

Cohort 2: ≥7 to <12 years TOL/TAZ 18/9 mg/kg

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.

Group Type: EXPERIMENTAL

Ceftolozane/Tazobactam 18/9 mg/kg

Intervention Type: DRUG

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

Cohort 3: ≥2 to <7 years TOL/TAZ 18/9 or 30/15 mg/kg

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.

Group Type: EXPERIMENTAL

Ceftolozane/Tazobactam 30/15 mg/kg

Intervention Type: DRUG

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

Ceftolozane/Tazobactam 18/9 mg/kg

Intervention Type: DRUG

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

Cohort 4: ≥3 months to <2 years TOL/TAZ 18/9 or 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.

Group Type: EXPERIMENTAL

Ceftolozane/Tazobactam 30/15 mg/kg

Intervention Type: DRUG

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

Ceftolozane/Tazobactam 18/9 mg/kg

Intervention Type: DRUG

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

Cohort 5: birth to <3 months TOL/TAZ 20/10 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.

Group Type: EXPERIMENTAL

Ceftolozane/Tazobactam 20/10 mg/kg

Intervention Type: DRUG

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

Cohort 6: birth to <3 months TOL/TAZ 12/6 or 20/10 mg/kg

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.

Group Type: EXPERIMENTAL

Ceftolozane/Tazobactam 20/10 mg/kg

Intervention Type: DRUG

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

Ceftolozane/Tazobactam 12/6 mg/kg

Intervention Type: DRUG

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

Interventions

Ceftolozane/Tazobactam 1000/500 mg

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

Intervention Type: DRUG

Ceftolozane/Tazobactam 30/15 mg/kg

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

Intervention Type: DRUG

Ceftolozane/Tazobactam 20/10 mg/kg

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

Intervention Type: DRUG

Ceftolozane/Tazobactam 18/9 mg/kg

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

Intervention Type: DRUG

Ceftolozane/Tazobactam 12/6 mg/kg

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

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 7 Days
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 30153232 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CXA-PEDS-13-08

Identifier Type: OTHER

Identifier Source: secondary_id

2014-003485-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-7625A-010

Identifier Type: OTHER

Identifier Source: secondary_id

7625A-010

Identifier Type: -

Identifier Source: org_study_id

NCT02725216

Identifier Type: -

Identifier Source: nct_alias