Steady-state Pharmacokinetics of Ceftazidime/Avibactam in Cystic Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Steady-state Pharmacokinetics of Ceftazidime/Avibactam in Cystic Fibrosis (NCT02504827), a na phase 4 study. The primary outcome is Peak Plasma Concentration (Cmax).

2. Clinical Question

This is a pharmacokinetic question: it concerns drug concentration in plasma following administration, rather than a comparison of clinical outcomes between treatment groups. Cmax describes the peak concentration, while the registry record's stated timeframe identifies when the endpoint was assessed. The record does not describe the blood-sampling schedule, how the peak was identified, or the timing of the concentration measurements in relation to each dose. Those details are not reported in the registry record.

Because there is no comparator group, the design does not directly address how concentrations differ from those in another population or under another regimen. The stated aim is characterization within the enrolled group. No hypothesis comparing groups, clinical efficacy endpoint, or treatment-effect estimate is listed. The registry record also does not report participant-level concentration data, so the spread of concentrations among participants cannot be assessed from the posted information.

3. Trial Design

This completed Phase 4 study is registered as a single-group investigation of ceftazidime/avibactam pharmacokinetics in cystic fibrosis. The registry lists an enrollment of 12 and one intervention group: IV Ceftazidime/Avibactam. Its described regimen was ceftazidime/avibactam 2.5gm IV q8h for 3 doses. The sponsor is the University of Southern California. The recorded start was 2015-09, and primary completion was 2016-10.

The design has no listed randomized allocation, masking, or control group. Allocation is marked NA, masking is marked none, and the model is single-group. Accordingly, the study is not a like-for-like comparison between arms. Its structure is consistent with describing pharmacokinetic measurements in the group receiving the intervention, but the exact measurement and analysis procedures are not reported in the registry record.

The registry identifies Peak Plasma Concentration (Cmax) as the primary outcome measure, with mg/L as the unit, mean as the parameter, full range as the dispersion, and 8 hours as the timeframe. It lists two outcome measures overall, but details for any additional outcome measure are not included in the available record. The number of analyses listed is zero. No analysis population, protocol deviations, or participant flow details are reported in the registry record.

The registry record does not describe a protocol-based sample-size justification, planned statistical analysis, interim analyses, or procedures for handling missing observations. These should not be inferred from the enrollment or from the endpoint summary format. Any sample-size illustrations associated with the posted results are planning exercises based on an observed effect, not evidence that the study was designed using those assumptions. In particular, planning power is not observed power and cannot substitute for the unreported design rationale.

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.

Overall Study

Reasons for not completing this period:

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 Peak Plasma Concentration (Cmax), measured over 8 hours.

Peak plasma concentration, or Cmax, is a pharmacokinetic measure of the highest concentration of a drug observed in plasma over a defined measurement period. The registry lists this endpoint in mg/L and specifies a timeframe of 8 hours. It identifies the reported parameter as the mean and the dispersion as the full range. The numerical mean and range are not reported in the registry record.

In general, concentration measures help describe how a drug appears in the bloodstream after administration. A peak concentration can characterize one part of that concentration profile; it does not by itself describe the full profile or all other aspects of exposure. Pharmacokinetic characterization can be useful for understanding measured drug concentrations in a particular study population. The stated purpose of this study was to characterize pharmacokinetics in patients with cystic fibrosis.

The registry does not explain how Cmax was operationally determined, what samples contributed to it, or whether it was a directly observed or model-derived value. The timeframe label does not by itself provide those procedural details. Sampling methods and any additional pharmacokinetic measures are not reported in the registry record. Without the numerical endpoint result, its range, and supporting measurement details, readers cannot assess the observed concentration level or the variability in the study group from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint labels describe the intended statistical structure, but they do not supply a complete analysis plan. The study is classified as single-group, with no comparator and no random allocation. Its primary measure is mean Cmax, with full range as the stated dispersion summary. The registry record does not report a statistical analysis method or a numerical result for that endpoint.

What does a single-group design estimate?

In general, a single-group study can describe measurements made in the participants who received the intervention. For a pharmacokinetic endpoint, a summary such as a mean can describe the concentration values in that group, if the data and analysis are reported. Such a description is not a randomized treatment contrast. Without a comparator group, differences attributable to treatment cannot be separated from differences that might arise from participant characteristics, measurement conditions, or other factors. The registry record lists no control arm or between-group analysis.

The intervention group received ceftazidime/avibactam 2.5gm IV q8h for 3 doses, as stated in the arm description. The registry does not say how long after administration samples were collected, how steady state was verified, or how the peak was identified. Although the title and study purpose refer to steady-state pharmacokinetics, the procedures used to establish or evaluate steady state are not reported in the registry record. No assumptions about those procedures should be read into the endpoint label.

What do mean and full range communicate?

In general, the mean is a summary of the central level of a set of numerical observations. It can provide a compact description, but it does not show every participant's value. The full range reports the lowest and highest values in the set being summarized. It conveys the span between the observed extremes, but gives little information about how values are distributed between those extremes. The registry specifies these summary types but does not post their numerical values.

In general, a confidence interval describes uncertainty around an estimated quantity under a stated statistical method. It is distinct from the range of individual observations: a range summarizes observed values, while an interval for a mean concerns uncertainty in estimating that mean. No confidence interval is reported for Cmax in the registry record, and the method for estimating uncertainty is not reported. Thus, neither the observed spread nor the precision of the mean can be evaluated from the posted endpoint information.

Why do analysis details matter?

Pharmacokinetic observations may be analyzed using methods appropriate to their timing and structure. In general, a concentration-time profile contains information beyond a single peak value; the measurement schedule and analytic approach determine which features can be estimated. The registry record does not describe the sampling design, whether the endpoint was directly observed or modeled, or how repeated measurements were handled. It is not possible to identify a specific pharmacokinetic model or infer that one was used.

In general, over-dispersion means that data vary more than a simple statistical model expects. When present, it can make standard errors and confidence intervals from an unsuitable model misleading. The registry record does not report a distributional model, a dispersion assessment, or an analysis requiring an over-dispersion adjustment. This general issue cannot be taken as evidence that over-dispersion occurred in this study.

The record lists zero analyses. It does not report a p-value, adjusted estimate, confidence interval, or a model-based comparison. The absence of such entries should not be filled in by assuming a conventional test or analysis plan. The registry record also does not report interim analyses, multiplicity procedures, missing-data methods, or a prespecified analysis population. Those details remain unknown.

Any recalculated statistic based on posted summary values would be an unadjusted calculation, not a replacement for the study's own analysis. No endpoint summary values are reported in the registry record for Cmax, so a recalculation of that endpoint is not available from the posted information. If a recalculated result disagrees with a sponsor analysis, the sponsor's own analysis takes precedence. No such discrepancy is identified in the registry record for this study.

Planning illustrations, when presented, answer a different question from the study results. In general, a sample-size calculation estimates how many participants might be needed under specified assumptions to detect a chosen effect with a chosen power and significance level. It does not measure the probability that the completed study detected an effect, and it is not observed power. The stated assumptions for planning illustrations are not the trial's own design rationale. A protocol-based sample-size justification is not reported in the registry record.

The central methodological conclusion is that the registry supplies design labels and a primary endpoint definition, but not enough results or analysis detail to assess the endpoint estimate. The mean and full range, the number of observations contributing to them, and the method used to derive Cmax are all necessary context for a fuller statistical interpretation; these are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures overall and identifies Peak Plasma Concentration (Cmax) as the primary endpoint. The details of the additional outcome measure are not reported in the registry record. It lists zero analyses and does not describe a testing hierarchy, adjustment for multiple comparisons, or any multiplicity strategy. Because no inferential analyses are reported, the record does not establish whether multiplicity was relevant to the investigators' planned analyses or how it would have been handled.

In general, multiplicity arises when multiple outcomes, timepoints, subgroups, or statistical tests are considered. Repeated testing can increase the chance of at least one apparently notable result by chance, depending on the analysis context. This is a general statistical consideration, not a claim that such testing occurred in this study. The registry record does not list enough analysis detail to determine the number of planned comparisons or whether adjustment was considered.

Missing-data handling is also not reported in the registry record. It does not state whether all enrolled participants contributed Cmax measurements, how incomplete concentration profiles were handled, or whether any observations were excluded. Enrollment of 12 does not establish the endpoint analysis count. The safety information lists 12 at risk in the intervention group, but that is not a report of the number contributing to the pharmacokinetic endpoint.

The analysis population is not reported in the registry record. In general, a clearly defined analysis population helps readers understand which participants and observations informed a result. The record does not say whether the endpoint was summarized for all enrolled participants, those who received the stated doses, or those with evaluable concentration measurements. Without these details, the reported design enrollment should not be treated as the endpoint denominator.

11. 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 5% reporting threshold.

The registry's adverse-event figures list 12 participants at risk in the IV Ceftazidime/Avibactam group. It reports zero participants affected by serious adverse events, zero affected by other adverse events, and zero deaths. No top serious adverse-event terms are listed. These are the posted safety counts for the group.

In general, an at-risk count identifies the group for which event reporting is summarized; it does not by itself describe the duration or completeness of surveillance. The registry record does not report the safety observation period, event collection procedures, definitions used, or whether all participants completed follow-up. The figures should therefore be read as the counts entered in the record, not as a complete characterization of every possible safety outcome.

A count of zero reported events does not establish that an intervention has no risks. It indicates that the registry record lists no affected participants for those categories in this group. The record does not provide event-level details, exposure-adjusted rates, or a comparator group. Because the study is single-group, these counts cannot support a comparative safety estimate.

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

The record establishes that a completed Phase 4, single-group study was undertaken to characterize the pharmacokinetics of intravenous ceftazidime/avibactam in people with cystic fibrosis. It identifies the regimen as 2.5gm IV q8h for 3 doses and names mean Cmax in mg/L at 8 hours as the primary endpoint, with full range as the dispersion summary. It also records enrollment of 12 and reports the safety counts for the intervention group.

The record does not report the numerical Cmax mean or full range. Consequently, it does not show the observed peak concentration, how much concentrations varied, or how precisely the mean was estimated. It does not provide an endpoint confidence interval, participant-level measurements, or an endpoint analysis count. The primary endpoint's designation is not itself evidence of a particular result.

The design also does not provide a randomized comparison. It cannot establish from the posted information how pharmacokinetic measurements compare with those under another regimen or in another group. No comparative clinical outcome is identified as the primary question. The study's stated aim is pharmacokinetic characterization, and the record does not report a clinical efficacy result.

The adverse-event entry records zero serious events, zero other events, and zero deaths among 12 at risk. Those registry counts do not establish absence of risk, and the record lacks details about follow-up and event ascertainment. Likewise, a completed status does not disclose whether every planned observation was collected or included in analysis.

The appropriate interpretation is limited to what the registry documents: the study design, regimen, endpoint definition, enrollment, and listed safety counts. The concentration result and several details needed to judge its measurement and analysis are not reported in the registry record. No conclusion about treatment benefit, comparative performance, or a broader population follows from these entries alone.

13. Why This Trial Matters Statistically

Pharmacokinetic studies address a different statistical question from trials designed to compare clinical outcomes. They describe concentrations associated with a drug regimen in a defined study group. For researchers, specifying a peak concentration endpoint, its units, timeframe, and summary form helps identify what the registry intends to report. In this study, those labels are mean Cmax in mg/L at 8 hours, with full range as the dispersion measure.

The single-group design makes the limits of interpretation especially important. A descriptive concentration result can characterize the enrolled group, but without a comparator it does not estimate a between-group difference. This distinction is useful when reading registry records: an endpoint can be clinically or scientifically relevant without being a comparative treatment-effect estimate. The record's stated purpose is pharmacokinetic characterization in cystic fibrosis.

The entry also illustrates why outcome definitions and numerical results need to be read separately. The registry names the primary endpoint but does not report its mean or range. Without those values, readers cannot assess either the observed concentration level or its variability. Nor can they evaluate precision without an uncertainty estimate and the analysis details that support it.

Finally, a completed status and safety counts are not substitutes for transparent reporting of the pharmacokinetic analysis. Sampling procedures, the endpoint analysis population, missing-data handling, and the actual result are not reported in the registry record. These details are important for evaluating how a concentration summary was obtained and how broadly it can be interpreted. The statistical value of this record is therefore in clarifying the study's question and design, while also making visible the limits created by unreported results and methods.

14. 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 statistical interpretation is that the registry record does not report the numerical result for the primary endpoint. It specifies mean Cmax and full range but provides neither value. As a result, the observed concentration and its variability cannot be assessed. No confidence interval or other precision measure is reported.

The endpoint measurement process is also insufficiently described. The record gives an 8 hours timeframe but does not report the sampling schedule, the method used to identify Cmax, or whether it was directly observed or derived using a model. It does not explain how steady state was evaluated, despite the study title referring to steady-state pharmacokinetics. These procedures are not reported in the registry record.

There is no comparator group, and the study is classified as single-group with allocation marked NA and masking marked none. The design therefore does not provide a randomized between-group contrast. The registry lists enrollment of 12 but does not state how many participants contributed evaluable endpoint measurements or define the analysis population. Missing-data and exclusion procedures are not reported in the registry record.

The record lists two outcome measures overall, but does not provide details for the additional measure. It lists zero analyses and does not describe statistical methods, interim analyses, multiplicity handling, or a sample-size justification. Safety reporting includes the listed counts but does not describe follow-up duration or event ascertainment. These omissions constrain interpretation of both the pharmacokinetic endpoint and safety entries. They do not establish that a procedure was absent; they mean the relevant information is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Steady-state Pharmacokinetics of Ceftazidime/Avibactam in Cystic Fibrosis — NCT02504827.
• Registry record last updated 2018-11-27; status last verified 2018-10.
• Results first posted 2018-11-27.
• 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.

18. Record Summary

This completed Phase 4 study examined the pharmacokinetics of intravenous ceftazidime/avibactam in people with cystic fibrosis. It was a single-group study sponsored by the University of Southern California, with enrollment of 12. The listed regimen was 2.5gm IV q8h for 3 doses.

The primary endpoint was mean Peak Plasma Concentration (Cmax), measured in mg/L at a timeframe of 8 hours, with full range specified as the dispersion summary. The numerical mean and range are not reported in the registry record. The record lists zero analyses and does not report the endpoint analysis population or methods for sampling and missing data.

For the intervention group, the registry lists 12 at risk, zero participants affected by serious adverse events, zero affected by other adverse events, and zero deaths. The record does not include a comparator group, and the safety follow-up details are not reported in the registry record.