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)

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

Status and phase: Completed; Phase 1

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

Treatments: Drug: Ceftolozane/Tazobactam 20/10 mg/kg; Drug: Ceftolozane/Tazobactam 18/9 mg/kg; Drug: Ceftolozane/Tazobactam 12/6 mg/kg; Drug: Ceftolozane/Tazobactam 1000/500 mg; Drug: Ceftolozane/Tazobactam 30/15 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02266706

CXA-PEDS-13-08 (Other Identifier)

7625A-010

2014-003485-24 (EudraCT Number)

MK-7625A-010 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 7 days to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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43 participants in 6 patient groups

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

Experimental group

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.

Treatment:

Drug: Ceftolozane/Tazobactam 1000/500 mg

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

Experimental group

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.

Treatment:

Drug: Ceftolozane/Tazobactam 18/9 mg/kg

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

Experimental group

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.

Treatment:

Drug: Ceftolozane/Tazobactam 30/15 mg/kg

Drug: Ceftolozane/Tazobactam 18/9 mg/kg

Cohort 4: ≥3 months to <2 years TOL/TAZ 18/9 or 30/15 mg/kg

Experimental group

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.

Treatment:

Drug: Ceftolozane/Tazobactam 30/15 mg/kg

Drug: Ceftolozane/Tazobactam 18/9 mg/kg

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

Experimental group

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.

Treatment:

Drug: Ceftolozane/Tazobactam 20/10 mg/kg

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

Experimental group

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.

Treatment:

Drug: Ceftolozane/Tazobactam 12/6 mg/kg

Drug: Ceftolozane/Tazobactam 20/10 mg/kg