A Study to Learn About the Study Medicine Called CTB+AVP in Healthy Adult People.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Learn About the Study Medicine Called CTB+AVP in Healthy Adult People. (NCT05554237), a randomized phase 1 study. The primary outcome is Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1.

2. Clinical Question

The registry describes a randomized, double-blind, sponsor-open, placebo-controlled, sequential phase one study in healthy adults. Its focus is early characterization of drug exposure and safety, rather than testing whether treatment improves a health outcome. The concentration endpoint helps describe exposure after dosing, while the reported safety outcomes describe adverse events during the study. Neither endpoint alone establishes the balance of benefits and harms for people being treated for complicated urinary tract infections.

3. Trial Design

The registry record identifies this as a phase one, randomized, double-blind, sponsor-open, placebo-controlled, sequential study. Its listed enrollment is 42. The record is marked completed, with a start date of 2022-10-07 and primary completion date of 2023-06-23. Pfizer is listed as the sponsor.

The trial had two parts. In Part 1, participants received increasing single doses of CTB and/or AVP. The primary endpoint concerns cis-ceftibuten maximum observed concentration in this part. The active Part 1 groups in the posted endpoint results were CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg, CTB 800 mg alone, CTB 1200 mg + AVP 1350 mg, and CTB 1600 mg alone; each group’s posted analysis count is 6.0. Placebo groups were also included in the trial, but do not appear among these five primary endpoint summaries.

Part 2 evaluated increasing multiple doses of CTB+AVP, described as three times a day for 7 days. The study summary says participants were closely monitored in an inpatient setting and describes blood sampling for study medicine levels and safety monitoring, including laboratory measurements and electrocardiograms. Maximum participation was described as up to 12 weeks for Part 1 and up to 10 weeks for Part 2, including screening and safety follow-up.

The registry labels the design randomized and double-blind, while also labeling it sponsor-open. The precise roles covered by masking and the sequence by which dose groups were opened or selected are not reported in the registry record. The detailed randomization method, allocation concealment process, and stopping rules are not reported in the registry record. The posted information therefore supports describing the broad design and dose-group structure, but not reconstructing how operational decisions were made within the sequential study.

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: A total of 42 participants (8 in Part 1 and 34 in Part 2) were enrolled in the study. The study was conducted at 1 site in Belgium.

Only the first 6 of 14 groups are shown.

Part 1: Period 1 Treatment (1 Day)

Part 1: Period 1 Washout (3 Days)

Part 1: Period 2 Treatment (1 Day)

Part 1: Period 2 Washout (3 Days)

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.

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.

Population: Full analysis set included all participants randomly assigned to study intervention and who take at least 1 dose of study intervention.

Only the first 6 of 15 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1, measured over pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose.

The primary endpoint is maximum observed concentration, abbreviated Cmax, of cis-ceftibuten in Part 1. It is measured in nanograms per milliliter (ng/mL). The endpoint is based on concentration measurements scheduled before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 14, and 24 hours after dosing. The registry reports the endpoint as a geometric mean, with geometric coefficient of variation as its dispersion measure.

Cmax is used in pharmacokinetic studies to describe the highest measured concentration reached over the sampling period. It offers one summary of systemic exposure after a dose. It does not describe the entire concentration-time profile: a measure such as area under the curve addresses exposure across time, while Cmax focuses on the observed peak. The scheduled samples also mean that the recorded maximum is the highest measured value, not necessarily the exact concentration at every moment between samples.

Geometric means are commonly used for concentration data because measurements may be distributed asymmetrically. In general, the geometric mean summarizes values on a multiplicative scale, rather than taking an ordinary arithmetic average of the original values. The coefficient of variation describes relative variability on the geometric scale. It is not a confidence interval and does not, by itself, show how precisely the group mean has been estimated.

This endpoint is pharmacokinetic, not a direct measure of symptom improvement or infection outcomes. It can inform understanding of exposure among the analyzed participants, but does not establish clinical efficacy or a treatment recommendation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean describe?

In general, a geometric mean is calculated on a transformed scale and then expressed on the original scale. It is useful when values behave multiplicatively or are skewed, as concentration measurements often can be. It gives a central summary that is less dominated by unusually high observations than an arithmetic mean may be. Here, the registry identifies the primary parameter as a geometric mean, and its dispersion as a geometric coefficient of variation. The record does not specify the exact computational handling of values or any below-quantification measurements.

How should the coefficient of variation be read?

In general, a coefficient of variation expresses variability relative to the scale of the measurements. A geometric coefficient of variation is associated with a log-scale summary. It describes how spread out observations are in relation to the geometric mean; it is not a range, a standard error, or a confidence interval for the mean. The posted values are therefore informative about within-group dispersion, but cannot substitute for uncertainty intervals around each dose-group estimate.

What does Cmax measure?

Cmax is the highest observed concentration over the measurement schedule. In this trial, samples were scheduled pre-dose and through 24 hours after dosing at the listed times. In general, a sampling schedule can miss a peak that occurs between scheduled draws. Thus, the endpoint is the maximum observed in the collected samples, rather than a continuously observed maximum. The registry’s wording and timepoints define the reported endpoint; the record does not report whether sampling times were altered for any participant.

How is the adjusted ratio different from group summaries?

The posted arm values are separate geometric means for each regimen. The sponsor’s reported analysis is an adjusted ratio of geometric means for CTB 800 mg + AVP 1350 mg compared with CTB 800 mg alone. In general, an adjusted comparison uses a specified statistical model or covariates to account for selected factors. Such adjustment can make the comparison differ from a ratio formed directly from unadjusted summaries. The registry does not report the model, covariates, or method used for this adjustment, so its details are not reported in the registry record.

A confidence interval gives a range of values compatible with the data and analysis under the method’s assumptions. The reported interval is a 90% confidence interval for the adjusted ratio. It reflects uncertainty in that comparison, not uncertainty in every arm summary and not the probability that a particular true value falls inside the interval. It does not provide evidence about clinical efficacy by itself. The registry reports no p-value for this comparison.

Why does the sequential design matter?

In general, sequential dose studies evaluate groups in an ordered development process, with dose selection informed by earlier experience or monitoring. This can be useful for early characterization and safety oversight. It also means that group comparisons may not have the same interpretation as a single, simultaneously randomized comparison of all doses. The record labels the study sequential, but does not report the operational sequence, decision criteria, or whether interim analyses were conducted. Those details are not reported in the registry record and should not be inferred from the dose ordering.

What can be learned from small group summaries?

Each listed primary endpoint group has an analysis count of 6.0. In general, estimates based on small groups can be sensitive to individual observations and may be imprecise. A geometric coefficient of variation helps describe observed spread, but without confidence intervals for the individual group estimates it does not quantify their estimation precision directly. It is therefore more appropriate to treat the group results as descriptive pharmacokinetic observations than as definitive estimates for a broad population.

How should planning calculations be understood?

In general, sample-size illustrations based on an observed effect ask how many participants per arm might be needed under stated assumptions to detect an effect of a chosen size. They are planning illustrations, not evidence that a study had a particular probability of detecting an effect and not a measure of what occurred in the completed trial. The registry does not report a sample-size justification for this study. Any posted planning illustration should be distinguished from the enrolled groups and from the sponsor’s analysis of the observed data.

How do missing results affect interpretation?

The registry lists 57 outcome measures and 31 analyses, while only 11 secondary outcomes are described as posted in the record. The presence of a large outcome listing does not mean that every measure has an interpretable result. The record notes that some values are missing or not estimable for a two-arm comparison for another endpoint. Missing or non-estimable results can limit assessment across outcomes, but the reason for each unavailable result is not reported in the registry record. No statistical approach to missing data is reported in the registry record.

10. Analyses Reported by the Sponsor

The registry reports a sponsor analysis for CTB 800 mg + AVP 1350 mg compared with CTB 800 mg alone. The result is an adjusted geometric-mean ratio of 83.46, with a 90% confidence interval from 74.67 to 93.29. It is not an unadjusted comparison of the five dose-group summaries, and it is not a p-value. The registry record does not identify the adjustment model or variables, so the adjustment cannot be independently reconstructed from the posted information.

The group summaries provide geometric means and geometric coefficients of variation for each active Part 1 regimen. Those descriptive values and the adjusted two-group ratio answer related but different questions. The ratio is specific to the named comparison; it should not be generalized to other doses or interpreted as a clinical outcome. The record does not report a discrepancy between the sponsor’s analysis and a recalculation. The sponsor’s stated result should therefore be read as the reported analysis, while recognizing that its modeling details are not reported in the registry record.

The 90% confidence interval indicates uncertainty under the sponsor’s analysis. Without the analysis specification, the interval’s assumptions and adjustment cannot be evaluated in detail. The registry reports no p-value for this comparison, and does not report confidence intervals for the individual group geometric means.

11. Multiplicity, Missing Data and Analysis Populations

The record lists several pharmacokinetic outcomes and analyses across the two study parts, including concentration, timing, exposure, urine excretion, and renal clearance measures. It also lists outcomes for Japanese and Chinese cohorts in Part 2. Such a collection of outcomes can involve multiple statistical comparisons. In general, making many comparisons increases the chance that at least one result appears notable by chance unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity adjustment, a hierarchy of confirmatory outcomes, or an interpretation framework for the family of analyses.

The primary endpoint is identified as maximum observed concentration of cis-ceftibuten in Part 1. The reported adjusted comparison has a 90% confidence interval, but the record does not explain why that confidence level was selected or how it relates to other analyses. A 90% interval should be interpreted as reported for that comparison, not as evidence that multiplicity was or was not controlled.

The pharmacokinetic analysis population is defined as participants randomly assigned to study intervention who took at least 1 dose and had at least 1 of the relevant pharmacokinetic parameters reported for the study part. This is not identical to an intention-to-treat definition. The number analyzed is given for each posted primary endpoint group, but the registry record does not report a full participant flow, reasons for exclusion, or a comparison of randomized and analyzed participants.

The missing-data approach, handling of measurements below quantification limits, and any imputation procedures are not reported in the registry record. The registry does not report whether interim analyses were planned or conducted, or whether stopping decisions used formal statistical boundaries. These omissions prevent a full assessment of how incomplete data or sequential decision-making may have affected the statistical results. Results should therefore be interpreted as the posted analyses, with those analysis details unresolved.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists serious adverse events and other adverse events by dose group. Across the listed groups, the count recorded as having a serious adverse event is 0, and the death count is 0. These are group-specific registry counts; they should not be combined into an overall total because participants may have participated in different cohorts or parts, and the record does not describe deduplication across groups.

For other adverse events, the listed affected counts vary by group. In Part 1, the counts are 2 for CTB 400 mg + AVP 900 mg, 3 for CTB 800 mg + AVP 1350 mg, 0 for CTB 800 mg alone, 3 for CTB 1200 mg + AVP 1350 mg, and 3 for CTB 1600 mg alone. The corresponding placebo groups list counts of 0, 1, 0, 1, and 0. In Part 2, the active groups list counts of 5, 4, and 5 for the stated regimens; Japanese and Chinese cohorts list 2 and 3. Their placebo groups list 2, 1, and 2 for the stated regimens, and 0 for the Japanese and Chinese cohorts.

These counts do not establish comparative safety. The group sizes differ, and the record does not report event definitions, severity details, relatedness assessments, exposure-adjusted rates, or the full event listings. The absence of recorded serious events in these groups is not proof that serious risk is absent.

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

The posted results characterize pharmacokinetic exposure to cis-ceftibuten after several Part 1 dose regimens in healthy adults. They report group geometric means, geometric coefficients of variation, and one adjusted geometric-mean ratio comparison. These results can help describe how measured peak concentrations varied among the studied groups. They are early-phase observations, not evidence of clinical benefit.

The study’s population and setting limit generalization. Participants were healthy adults meeting specified eligibility criteria, and study treatment was administered under close inpatient monitoring. The record describes development of CTB+AVP for complicated urinary tract infections, but the primary endpoint is a concentration measurement rather than infection response. The trial results do not establish efficacy in people with infection, nor do they identify a preferred regimen for clinical use.

The result also does not establish that all dose regimens have equivalent exposure or safety. The five group means are descriptive, group sizes are limited, and the reported adjusted comparison covers only two regimens. A confidence interval around that ratio does not answer questions about all other arms, patient outcomes, or longer-term effects. Safety counts are similarly specific to the posted groups and observation period.

In general, pharmacokinetic findings can inform later research by describing exposure after different regimens. Additional evidence would be needed to assess clinical outcomes and characterize safety in the intended patient population. The registry record does not report such evidence as part of this trial. No medical decision should be based on these concentration summaries alone.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a pharmacokinetic endpoint and a clinical outcome. Maximum observed concentration describes measured exposure, while an outcome such as infection response would address a different question. Keeping those questions separate prevents a concentration result from being overstated as evidence of clinical effectiveness.

The record also shows why the estimand and analysis population matter. The primary endpoint uses a defined pharmacokinetic set, not simply everyone enrolled. A concentration summary is meaningful in relation to its dosing regimen, sampling schedule, and analyzed participants. The posted schedule makes clear that the maximum is based on sampled observations, while group-level summaries and a separate adjusted ratio provide different statistical views.

Sequential dose evaluation has a distinct purpose from a conventional, fixed comparison of treatments. It can support early study of increasing doses, but makes it important to know how cohorts were ordered and how dose decisions were made. Those operational details are not reported in the registry record. Similarly, small group summaries are useful for characterization but provide limited precision and do not automatically support broad comparisons.

Finally, the posted safety counts show the value of reading event counts by cohort rather than collapsing across groups. Group sizes and regimens differ, and the record does not provide enough detail to produce standardized safety comparisons. Together, these features make the trial statistically informative as an early pharmacokinetic study while marking clear boundaries around what its results can establish.

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.

Several trial-specific limitations affect interpretation. The primary endpoint is based on a small pharmacokinetic analysis population: each of the five listed active Part 1 groups has an analysis count of 6.0. The registry provides geometric means and geometric coefficients of variation but no confidence intervals for those individual group summaries. This leaves their estimation precision less directly characterized than the reported adjusted two-group comparison.

The listed primary endpoint groups differ in the drug components and dose levels administered. The results should not be read as a complete dose-response comparison or as isolating the contribution of CTB or AVP across all regimens. The study is described as sequential, but the sequence and decision rules are not reported in the registry record. The masking label is double-blind and sponsor-open, but the exact roles and procedures covered are not reported in the registry record.

The sponsor-reported ratio is adjusted, but the model and adjustment variables are not reported in the registry record. The registry provides no p-value for that analysis. It also does not report a statistical analysis plan, multiplicity handling, interim analyses, missing-data procedures, or the rationale for the confidence level used. These gaps constrain assessment of the analysis assumptions and of how the reported comparison fits among the multiple outcomes.

The study enrolled healthy adults, so its findings do not directly characterize exposure or safety in people with complicated urinary tract infections. Safety reporting gives group-level counts, but detailed event terms, severity, relationship to treatment, and standardized rates are not reported in the registry record. The record’s absence of serious events and deaths in the listed groups should be interpreted as a description of those reported observations, not as proof of no risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Learn About the Study Medicine Called CTB+AVP in Healthy Adult People. — NCT05554237.
• Registry record last updated 2024-10-10; status last verified 2024-06.
• Results first posted 2024-10-10.
• 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

The registry record describes a completed, randomized, double-blind, sponsor-open, placebo-controlled, sequential phase one study sponsored by Pfizer, with enrollment of 42. It evaluated single-dose CTB and/or AVP regimens in Part 1 and multiple-dose CTB+AVP regimens in Part 2 among healthy adult participants.

The primary endpoint was geometric mean maximum observed concentration of cis-ceftibuten in Part 1, measured in ng/mL, with geometric coefficient of variation reported as dispersion. Five active Part 1 dose groups have posted summaries. The registry also reports an adjusted geometric-mean ratio of 83.46, with a 90% confidence interval from 74.67 to 93.29, for CTB 800 mg + AVP 1350 mg compared with CTB 800 mg alone.

Serious adverse-event and death counts are 0 in each listed group. Other adverse-event counts vary by group. The record does not report enough statistical-plan or model detail to fully reconstruct the analyses, and the primary endpoint is pharmacokinetic rather than clinical efficacy.