A Phase 1, open-label, non-comparative, multicenter clinical study to evaluate the safety, tolerability, and pharmacokinetics of ceftolozane/tazobactam (MK-7625A) in pediatric participants with nosocomial pneumonia

The primary objective of this Phase 1, open-label, non-comparative, multicenter clinical study is to evaluate the **safety** and **tolerability** of ceftolozane/tazobactam in pediatric participants diagnosed with nosocomial pneumonia. This is clinically relevant as it aims to ensure that the treatment is safe for use in a vulnerable population, such as children, who are affected by hospital-acquired infections, which can be severe and challenging to treat.

Secondary objectives include:

• Evaluating the **pharmacokinetics** (PK) of multiple doses of ceftolozane/tazobactam for each age group and/or dose level. This is important to understand how the drug is absorbed, distributed, metabolized, and excreted in pediatric patients, which can inform dosing regimens and optimize therapeutic outcomes.

The clinical trial involves a total of **53 participants** who are being evaluated for the safety and tolerability of ceftolozane/tazobactam in the treatment of **nosocomial infection, specifically pneumonia**. The study population includes both male and female subjects, with an age range that encompasses adults. Participants were selected based on their hospitalization status and the anticipation of receiving a minimum of 8 days of concomitant standard-of-care antibiotic therapy for proven or suspected nosocomial pneumonia. The trial includes a vulnerable population, indicating that special considerations are in place for their participation. Lifestyle factors such as diet and physical activity are not specified, but the trial does require specific contraceptive measures for both male and female participants to ensure safety during the intervention period. The inclusion criteria emphasize the need for participants to be either abstinent or using acceptable contraception, with additional requirements for women of childbearing potential to have a negative pregnancy test prior to the study intervention.

The clinical trial is a Phase 1, open-label, non-comparative, multicenter study designed to evaluate the **safety**, tolerability, and pharmacokinetics of **ceftolozane/tazobactam** in pediatric participants diagnosed with nosocomial pneumonia. The trial employs a non-randomized design, focusing on the collection of safety and pharmacokinetic data without a control group. The study is expected to span from May 26, 2020, to September 22, 2025, with participant involvement anticipated to last for a minimum of 8 days, aligning with the duration of concomitant standard-of-care antibiotic therapy.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as hospitalization status and the need for antibiotic therapy. Subsequent visits will involve the administration of the study drug via **intravenous infusion** and the collection of blood samples to assess plasma concentrations of ceftolozane and tazobactam. Follow-up visits will monitor for any adverse events (AEs) or serious adverse events (SAEs), with particular attention to those related to the study drug. The end-of-study visit will conclude the participant's involvement, ensuring all safety assessments are complete.

Participants may be withdrawn from the study early if they experience any AEs leading to discontinuation of the study intervention or if they no longer meet the inclusion criteria. The primary endpoints include the percentage of participants experiencing any AEs, SAEs, drug-related AEs, and drug-related SAEs. Secondary endpoints focus on pharmacokinetic parameters such as plasma concentrations, area under the concentration-time curve (AUC), maximum observed concentration (Cmax), elimination half-life (t1/2), volume of distribution (Vd), and clearance (CL) of both ceftolozane and tazobactam. The trial aims to provide comprehensive data on the safety and pharmacokinetic profile of the study drug in the pediatric population with nosocomial pneumonia.

The clinical trial involves the administration of **Zerbaxa**, a combination of two active substances: **tazobactam** and **ceftolozane**. This investigational medication is provided in the form of a powder for concentrate, which is then prepared as a solution for infusion. The pharmaceutical form is specifically designed for **intravenous infusion**, ensuring direct delivery into the bloodstream. The product is manufactured by Merck Sharp & Dohme BV and is identified by the marketing authorization number EU/1/15/1032/001. The trial aims to evaluate the safety, tolerability, and pharmacokinetics of this medication in pediatric participants diagnosed with nosocomial pneumonia. The dosing schedule and frequency of administration are determined by the study protocol, with careful monitoring to ensure participant compliance.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on the investigational product, Zerbaxa, to assess its effects in the specified patient population. The trial is open-label and non-comparative, allowing for direct observation of the medication's impact without the influence of additional treatments. Compliance with the dosing regimen is monitored through established clinical trial procedures to ensure accurate data collection and analysis.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on safety and tolerability, measured by the percentage of participants experiencing any adverse events (AEs), serious adverse events (SAEs), drug-related AEs, drug-related SAEs, and AEs leading to discontinuation of the study intervention. These parameters will provide insight into the safety profile of the investigational product, **ceftolozane/tazobactam**, in pediatric participants with nosocomial pneumonia.

The secondary endpoints are centered on pharmacokinetic parameters, which include plasma concentrations of ceftolozane and tazobactam, steady-state plasma area under the concentration-time curve (AUC0-8) for both compounds, maximum observed concentration (Cmax) during a dosage interval, elimination half-life (t1/2), volume of distribution (Vd), and clearance (CL). These measurements will be collected and analyzed to understand the pharmacokinetic profile of the drug combination in the target population. The data collection will occur at specified intervals to ensure comprehensive pharmacokinetic profiling.