Safety and Pharmacokinetics of Ceftolozane/Tazobactam in Pediatric Participants With Nosocomial Pneumonia (MK-7625A-036): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Pharmacokinetics of Ceftolozane/Tazobactam in Pediatric Participants With Nosocomial Pneumonia (MK-7625A-036) (NCT04223752), a non-randomized phase 1 study. The primary outcome is Percentage of Participants With Any Adverse Events (AEs).

2. Clinical Question

The study also assessed tolerability and pharmacokinetics. Listed pharmacokinetic outcomes include plasma concentrations of ceftolozane and tazobactam, along with measures such as concentration-time exposure, maximum observed concentration, elimination half-life, clearance, and volume of distribution for ceftolozane. The listed outcomes describe what was intended for assessment; observed pharmacokinetic results are not reported in the registry record.

3. Trial Design

This was a phase 1, open-label, non-comparative, multicenter clinical study of ceftolozane/tazobactam in pediatric participants with nosocomial pneumonia. The registry lists an enrollment of 41 and a completed status. The study began on 2020-04-17, with primary completion on 2024-09-14.

Participants were organized into five age groups: 12 to <18 years, 7 to <12 years, 2 to <7 years, 3 months to <2 years, and birth to <3 months. Each group received intravenous ceftolozane/tazobactam every 8 hours for 8-14 days. These age bands describe the study’s dosing groups; they do not create a randomized comparison between different treatments.

Allocation was non-randomized, masking was absent, and the overall study model was single-group. There was no concurrent control group listed. As a result, differences in adverse-event counts between age groups should not be interpreted as treatment effects or as evidence that one age group had a different underlying risk. The groups may differ in ways that the registry record does not describe, and the study was not presented as a controlled comparison.

The primary endpoint was the percentage of participants with any adverse event up to 31 days. The analysis population included participants who received any dose, including a partial dose. Pharmacokinetic outcomes were also listed. The registry record does not report the protocol’s rationale for enrollment, a sample-size justification, or a detailed statistical analysis plan.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: One participant was enrolled in error in the Group 5 arm and was excluded from the All participants as treated (APaT) population; the participant did not receive study intervention.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population consisted of participants who received any dose (including partial doses) of ceftolozane/tazobactam.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Any Adverse Events (AEs), measured over Up to 31 days.

The primary endpoint was the percentage of participants experiencing any adverse event up to 31 days. An adverse event was defined as an untoward medical occurrence temporally associated with use of the study intervention, whether or not it was considered related to that intervention. The endpoint therefore captures events occurring during the defined observation period without requiring that investigators judge the drug to have caused them.

Counting any adverse event is a broad safety measure. It can identify the proportion of the analysis population with at least one recorded event, but by itself it does not describe event severity, seriousness, duration, or causal attribution. Those features require separate information. The registry description says the percentage was reported for each arm; in this study, the age-based groups are not randomized comparison arms.

The endpoint used a population of participants who received any dose, including partial doses. This defines who contributes to the safety analysis and is not necessarily the same as every person enrolled. The registry record does not report the primary endpoint percentages or confidence intervals, so the observed value and its precision cannot be assessed from the posted results. The endpoint is useful for describing safety experience in the studied participants, but it cannot establish comparative safety without a suitable control group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry lists a binary percentage endpoint: the percentage of participants with at least one adverse event. This is a participant-level summary. It differs from a count of all event episodes, because a participant with multiple events may still contribute once to a percentage based on whether any event occurred. The endpoint definition includes untoward medical occurrences temporally associated with study intervention, regardless of whether they were considered related.

What does a confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimated quantity under a specified statistical procedure. For a percentage, it gives a range of values compatible with the observed data and method, rather than a guarantee about the true value. Wider intervals generally indicate less precision, while narrower intervals indicate greater precision. The primary endpoint lists a 95% confidence interval as its dispersion measure, but the interval itself is not reported in the registry record. The interval method is also not reported in the registry record.

Why does the analysis population matter?

The primary analysis population consisted of participants who received any dose, including partial doses. That definition determines who contributes to the endpoint estimate. It is a safety-oriented population definition, but the registry record does not describe how participants with missing endpoint information were handled. It also does not report whether any participants were excluded from this population or give a participant-level accounting of missing observations.

The enrolled population and the endpoint analysis population need not be identical in a clinical study, because eligibility for an analysis can depend on receiving the intervention or having relevant measurements. Here, the registry states the analysis population definition but does not report the detailed disposition or missing-data procedures. No assumptions about those procedures can be made from the record.

What can age-group counts show?

Counts by age group are descriptive. In a randomized comparison, treatment groups are assigned in a way intended to support a causal comparison. This study was non-randomized and single-group, and the groups correspond to different ages. Therefore, differences in their counts may reflect differences in group composition, clinical circumstances, or chance, as well as any other factors. The counts alone cannot isolate a treatment effect or an age effect.

General statistical principle: comparisons between small groups can be imprecise, and a difference in observed counts does not by itself establish a reliable difference in underlying risk. A confidence interval can help convey uncertainty, but group-specific confidence intervals for these counts are not reported in the registry record. No adjusted analysis is reported.

How should the planning illustration be read?

The sample-size planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes planning for a stated fraction of an observed effect; for time-to-event outcomes it specifies total events, and for other outcomes it specifies participants per arm. These are planning assumptions, not the design details of this trial. The record characterizes the illustration as computed from the observed effect, not as the trial’s own design. Such planning figures are not observed power and do not supply evidence about the intervention’s effects. No specific planning values or observed effect are reported in the registry record.

What analysis details are absent?

The registry record reports 17 outcome measures and no analysis entries. It does not report the statistical test or interval procedure used for the primary endpoint, adjustment for covariates, interim analyses, or a multiplicity strategy. It also does not report numerical pharmacokinetic results. The secondary outcomes list concentration measurements and pharmacokinetic parameters, but outcome names alone do not show their estimated values or precision.

In general, pharmacokinetic parameters describe how drug concentrations change over time and how the body handles a compound. Concentration-time exposure, maximum concentration, half-life, clearance, and volume of distribution each summarize different aspects of those measurements. Their interpretation depends on the actual measurements, sampling schedule, analysis approach, and population. Those details and results are not reported in the registry record, so no pharmacokinetic conclusions can be drawn from the outcome list alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Group 1: Ceftolozane/Tazobactam 12 to <18 Years of", "Group 2: Ceftolozane/Tazobactam 7 to <12 Years of ", "Group 3: Ceftolozane/Tazobactam 2 to <7 Years of A", "Group 4: Ceftolozane/Tazobactam 3 Months to <2 Yea", "Group 5: Ceftolozane/Tazobactam Birth to <3 Months")
n      <- c(8, 7, 8, 10, 7)
events <- c(4, 5, 6, 9, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Group 1: Ceftolozane/Tazobactam 12 to <18 Years of  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8
ARM  Group 2: Ceftolozane/Tazobactam 7 to <12 Years of   7  5  71.4  29.0  96.3  35.9  91.8  34.9  91.5
ARM  Group 3: Ceftolozane/Tazobactam 2 to <7 Years of A  8  6  75.0  34.9  96.8  40.9  92.9  40.0  92.5
ARM  Group 4: Ceftolozane/Tazobactam 3 Months to <2 Yea  10  9  90.0  55.5  99.7  59.6  98.2  58.7  97.7
ARM  Group 5: Ceftolozane/Tazobactam Birth to <3 Months  7  6  85.7  42.1  99.6  48.7  97.4  47.3  96.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary safety endpoint and pharmacokinetic outcomes. It reports no analysis entries. A multiplicity approach—how inference is handled when several outcomes or comparisons are assessed—is not reported in the registry record. In general, examining multiple outcomes can increase the chance of apparently notable findings arising by chance, so a prespecified analysis plan can clarify which findings are confirmatory and how other analyses should be interpreted. The record does not state whether such a plan included a multiplicity adjustment.

Missing-data handling is also not reported in the registry record. The primary analysis population is defined as participants who received any dose, including partial doses, but the record does not describe how missing adverse-event observations or incomplete follow-up were handled. It does not report whether all participants in that population contributed complete observations through the endpoint timeframe.

The listed population definition should not be mistaken for a complete account of analysis procedures. The registry record does not report the statistical model, endpoint-specific denominators beyond the adverse-event group counts, covariate adjustment, or sensitivity analyses. It also does not provide numerical results for the pharmacokinetic outcomes. These omissions limit assessment of how robust the reported safety counts are to missing information and how uncertainty was handled across outcomes.

In general, transparent reporting of analysis populations, missingness, and multiplicity helps readers distinguish planned primary analyses from exploratory findings. Without those details in the registry record, conclusions should remain descriptive and restricted to the results actually posted.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiogenic shock (14.3%), bacterial sepsis (14.3%), candida infection (14.3%), urinary tract infection (14.3%), benign mediastinal neoplasm (14.3%).

The registry lists serious adverse-event counts by age group. The reported counts are 1 of 8 for Group 1, 2 of 7 for Group 2, 0 of 8 for Group 3, 3 of 10 for Group 4, and 2 of 7 for Group 5. Other adverse-event counts are listed separately: 4 of 8, 5 of 7, 6 of 8, 9 of 10, and 6 of 7, respectively. These counts should be read as group-specific descriptions, not as a controlled comparison.

Deaths are listed as 0 in Group 1, 0 in Group 2, 0 in Group 3, 2 in Group 4, and 1 in Group 5. A death count records an outcome, but does not by itself establish its cause or relationship to the intervention. Causal attribution for these deaths is not reported in the registry record.

The listed serious adverse-event terms are cardiogenic shock, bacterial sepsis, Candida infection, urinary tract infection, benign mediastinal neoplasm, and device dislocation, each reported as 14.3%. The record does not provide further context for those term percentages. Seriousness and severity are not interchangeable concepts in general: seriousness concerns outcomes or consequences, while severity describes intensity. The registry counts alone do not supply enough detail to characterize each event’s course or attribution.

13. What the Result Does, and Does Not, Mean

This study’s posted information is best understood as a descriptive safety and pharmacokinetic record for pediatric participants with nosocomial pneumonia who received ceftolozane/tazobactam. It documents five age-based dosing groups and lists adverse-event counts and selected serious adverse-event terms. It does not report the primary endpoint percentage or its confidence interval, and it does not report numerical pharmacokinetic results.

The study design does not support a like-for-like comparison of treatment with a control. It was open-label, non-randomized, and single-group, with no comparator listed. The age groups differ by age rather than assigned treatment, so differences between their adverse-event counts cannot be taken as evidence that treatment effects vary by age. The counts also cannot establish whether events were caused by the intervention.

The information does not answer whether ceftolozane/tazobactam is more or less effective than another treatment, because the primary question and posted results concern safety and pharmacokinetics, and no comparative efficacy outcome is reported. It also does not establish that the intervention is safe or unsafe overall. The missing primary endpoint estimate and confidence interval prevent assessment of the main safety measure’s observed magnitude and precision.

General interpretation: an adverse-event percentage describes how often participants experienced an event according to a defined endpoint; it does not by itself establish causation. A confidence interval would help convey uncertainty around such an estimate, but the record does not report the primary interval. The serious-event counts and death counts are important descriptive information, but require context about event timing, clinical circumstances, and attribution to support more detailed interpretation. Such context is not reported in the registry record.

14. Why This Trial Matters Statistically

Phase 1 studies can provide early clinical information about safety, tolerability, and drug concentrations in a population for which the registry identifies a pediatric indication of interest. This study includes five age bands, extending from birth to <3 months through 12 to <18 years, and lists pharmacokinetic measures alongside adverse-event monitoring. Those features make clear that the record’s focus is not a comparative efficacy estimate.

Statistically, the design illustrates the difference between describing an experience and estimating a causal contrast. A single-group, open-label, non-randomized study can report what was observed among participants receiving the intervention. Without a concurrent control group, it cannot separate intervention-associated events from events that might occur because of the underlying condition, other care, or other circumstances. Non-randomized age groups do not resolve that limitation.

The record also shows why endpoint estimates and their uncertainty matter. The primary endpoint is clearly defined, and a 95% confidence interval is specified as the dispersion measure, but neither the primary percentage nor its interval is reported in the registry record. Counts of serious events provide useful descriptive detail, yet they do not replace an estimate of the prespecified primary endpoint or its precision.

Finally, a list of pharmacokinetic outcomes is not itself a pharmacokinetic result. Interpretation would depend on the observed concentrations and parameter estimates, along with their analysis and uncertainty. Those numerical findings are not reported in the registry record. The study is therefore statistically informative about design and intended measurement, while the posted outcome information supports only a limited descriptive reading.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpreting the main safety question is that the primary endpoint result is not reported in the registry record. Although the endpoint is defined as the percentage with any adverse event up to 31 days and a 95% confidence interval is specified, neither the percentage nor the interval is available in the posted results. The listed adverse-event counts do not supply that missing result.

The study had no control group and was not randomized or masked. It therefore cannot provide a direct comparative estimate, and event counts cannot establish causality. The age groups are not like-for-like treatment groups; age-specific differences may have several explanations that the registry record does not resolve.

Numerical results for the listed pharmacokinetic outcomes are not reported in the registry record. The record also does not provide the primary endpoint’s interval method, a detailed statistical analysis plan, a sample-size justification, interim-analysis information, multiplicity handling, or missing-data procedures. These details are relevant to evaluating precision and the robustness of results.

Some safety information is presented as group counts and serious-event terms, but the record does not provide further event-level context or causal assessments for deaths. The six serious-event terms are each listed as 14.3%, without additional denominator context in the record excerpt. These constraints mean that the available information supports a limited descriptive interpretation rather than a comprehensive assessment of comparative safety, causation, or pharmacokinetics.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Pharmacokinetics of Ceftolozane/Tazobactam in Pediatric Participants With Nosocomial Pneumonia (MK-7625A-036) — NCT04223752.
• Registry record last updated 2025-09-22; status last verified 2025-08.
• Results first posted 2025-09-22.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT04223752 is a completed phase 1, open-label, non-comparative, multicenter study of intravenous ceftolozane/tazobactam in pediatric participants with nosocomial pneumonia. The registry lists an enrollment of 41, non-randomized allocation, no masking, and a single-group model. Study groups covered five age bands from birth to <3 months through 12 to <18 years; dosing was every 8 hours for 8-14 days.

The primary endpoint was the percentage of participants with any adverse event up to 31 days among participants who received any dose. Group-level serious and other adverse-event counts and death counts are reported. The primary endpoint percentage and confidence interval, as well as numerical pharmacokinetic results, are not reported in the registry record. The design is descriptive and does not provide a randomized treatment comparison.