Phase 1
Completed N=43
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)
Proven or Suspected Gram-negative Bacterial Infection · Peri-operative Prophylaxis
Source: ClinicalTrials.gov NCT02266706 ↗
Enrolled (actual)
43
Serious AEs
8.1%
Results posted
Feb 2019
Primary outcomePrimary: Maximum Plasma Concentration (Cmax) of Ceftolozane — 63.5; 56.2; 51.4; 96.6 μg/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Plasma Concentration (Cmax) of Ceftolozane |
63.5; 56.2; 51.4; 96.6; 50.5; 91.3 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Tazobactam |
14.0; 9.25; 15.7; 24.8; 11.6; 22.4 | — |
| PRIMARY Time to Maximum Plasma Concentration (Tmax) of Ceftolozane |
1.02; 1.07; 1.02; 1.03; 1.00; 1.05 | — |
| PRIMARY Time to Maximum Plasma Concentration (Tmax) of Tazobactam |
1.00; 1.07; 1.02; 1.03; 1.00; 1.05 | — |
| PRIMARY Plasma Concentration at the Last Quantifiable Concentration (Clast) of Ceftolozane |
4.01; 2.85; 2.47; 5.69; 2.53; 5.72 | — |
| PRIMARY Plasma Concentration at the Last Quantifiable Concentration (Clast) of Tazobactam |
0.232; 0.420; 0.137; 0.327; 0.224; 0.401 | — |
| PRIMARY Time of Last Sampling Point (Tlast) of Ceftolozane |
6.00; 6.01; 6.08; 5.77; 6.00; 6.00 | — |
| PRIMARY Time of Last Sampling Point (Tlast) of Tazobactam |
4.15; 3.10; 5.85; 5.72; 4.00; 5.02 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve (AUClast) of Ceftolozane |
124; 102; 94.2; 172; 98.8; 178 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve (AUClast) of Tazobactam |
17.3; 9.69; 17.6; 28.5; 14.8; 28.9 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Ceftolozane |
133; 107; 99.4; 186; 103; 202 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Tazobactam |
17.5; 10.2; 17.8; 28.9; 14.9; 29.9 | — |
| PRIMARY Elimination Half-life (t1/2) of Ceftolozane |
1.45; 1.29; 1.34; 1.48; 1.30; 1.63 | — |
| PRIMARY Elimination Half-life (t1/2) of Tazobactam |
0.702; 0.544; 0.719; 0.770; 0.538; 0.815 | — |
| PRIMARY Volume of Distribution at Steady State (Vss) of Ceftolozane |
0.274; 0.296; 0.331; 0.312; 0.282; 0.340 | — |
| PRIMARY Volume of Distribution at Steady State (Vss) of Tazobactam |
0.474; 0.740; 0.488; 0.513; 0.421; 0.574 | — |
| PRIMARY Plasma Clearance (CL) of Ceftolozane |
0.146; 0.168; 0.181; 0.162; 0.176; 0.149 | — |
| PRIMARY Plasma Clearance (CL) of Tazobactam |
0.556; 0.886; 0.506; 0.519; 0.611; 0.502 | — |
| SECONDARY Number of Participants With One or More Adverse Events |
2; 1; 1; 1; 1; 2 | — |
| SECONDARY Number of Participants Who Discontinued the Study Due to an Adverse Event |
0; 0; 0; 0; 0; 0 | — |
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
Data sourced from ClinicalTrials.gov (NCT02266706). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.