Pharmacokinetic Study of Gepotidacin in Subjects With Varying Degrees of Renal Impairment and in Subjects With Normal Renal Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic Study of Gepotidacin in Subjects With Varying Degrees of Renal Impairment and in Subjects With Normal Renal Function (NCT02729038), a non-randomized phase 1 study. The primary outcome is Area Under the Plasma Concentration Time Curve (AUC) From Hour 0 to Infinity (AUC[0-inf]) of Gepotidacin for Part 1.

2. Clinical Question

3. Trial Design

This was a Phase I, open-label, non-randomized, parallel-group, multi-center, multi-part study of a single dose of gepotidacin. The registry lists enrollment of 32 and status as completed. The recorded study start was 2016-06-29, and primary completion was 2017-06-20.

Part 1 included subjects with normal renal function, moderate renal impairment, and severe renal impairment or ESRD not on hemodialysis. The registry description says normal-function participants were matched to participants in the impaired-function groups. It does not report the matching variables, how matching was carried out, or whether the planned matching was achieved. Part 2 was optional and concerned normal renal function, mild renal impairment, and ESRD on hemodialysis. The primary endpoint applies to Part 1.

Across the described groups, the study intervention was gepotidacin 750 mg given as a 2 hour intravenous infusion. The hemodialysis group description refers to dosing in relation to a dialysis session, but its full schedule is not reported in the registry record. There was no placebo or separate active treatment described; the comparison of interest was pharmacokinetic exposure across renal-function groups.

Because allocation was non-randomized and masking was absent, this design is best understood as a pharmacokinetic comparison, not a randomized treatment-effect trial. Renal-function groups could differ in ways beyond renal status, and open-label status means treatment was not masked. Those design features do not invalidate measurement of plasma concentrations, but they matter when interpreting group comparisons. The registry record does not report a detailed protocol, a sample-size justification, or the procedures used to manage possible differences between groups.

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 43 participants were screened of which 8 were screen-failures and 32 were enrolled in the study and 3 participants were reserve participants and were no longer required in the study .

Part 1 (Up to 44 Days)

Part 2 (Up to 50 Days)

Analysis population for the primary outcome, as defined in the registry: PK Parameter Population.

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 Area Under the Plasma Concentration Time Curve (AUC) From Hour 0 to Infinity (AUC[0-inf]) of Gepotidacin for Part 1, measured over Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose..

The primary endpoint was AUC[0-inf] of gepotidacin in plasma for Part 1, expressed in nanogram*hour per milliliter. AUC represents the area under the concentration-time curve: in general, it summarizes drug exposure over the measured interval and, for this endpoint, extends from hour 0 to infinity by extrapolation. Blood samples were collected before dosing and at the post-dose times specified in the registry.

The endpoint is a pharmacokinetic measure rather than a clinical measure of infection symptoms or treatment response. Comparing AUC across renal-function groups can help describe whether plasma exposure differs with renal status after the same stated dose. That is relevant to the study objective of informing whether renal-impairment dosing recommendations may be needed, but the endpoint alone does not establish a dosing recommendation or a clinical benefit.

The registry specifies a geometric mean as the summary measure and a geometric coefficient of variation as the dispersion measure. In general, geometric summaries are useful for positive measurements that vary multiplicatively or are skewed: they describe a typical level on a multiplicative scale. A geometric coefficient of variation describes relative spread on that scale. The registry record does not report the numerical geometric means, dispersion estimates, or group contrasts for this endpoint, so the size and precision of any exposure differences cannot be assessed from the recorded results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information recorded for the primary endpoint centers on plasma concentration measurements and a derived pharmacokinetic summary. The endpoint is AUC[0-inf], with a geometric mean and geometric coefficient of variation specified for reporting. The registry identifies the PK Parameter Population as participants in the PK Population for whom valid and evaluable pharmacokinetic parameters were derived. The PK Population consisted of participants who received at least one dose of gepotidacin and had evaluable PK data.

What does AUC represent?

In general, area under a concentration-time curve summarizes exposure over time. AUC[0-inf] begins at hour 0 and extends to infinity through extrapolation from the observed concentration-time information. The registry lists blood collection before dosing and at specified post-dose time points, through 48 hours. The endpoint therefore combines information across multiple measurements rather than representing a single concentration reading. The record does not describe the calculation details, extrapolation method, or criteria for deciding whether a derived parameter was valid and evaluable.

Why report a geometric mean?

As a general statistical explanation, positive pharmacokinetic measurements can vary multiplicatively, and their distributions may be asymmetric. A geometric mean summarizes values on a logarithmic scale and then expresses the summary on the original scale. It is therefore suited to describing a typical value when proportional differences are more meaningful than fixed additive differences. The geometric coefficient of variation is a measure of relative dispersion around such a summary. It helps communicate how much measurements vary in proportional terms. No numerical geometric means or geometric coefficients of variation for the primary endpoint are reported in the registry record.

What would a comparison tell the reader?

In general, a group contrast would quantify how exposure in a renal-function group relates to exposure in a comparison group. An estimate describes the size and direction of the contrast; an interval estimate describes its precision under the analysis assumptions. A p-value, if used, addresses compatibility with a specified null model and is not a measure of clinical importance. The registry record does not report the primary endpoint contrasts, confidence intervals, p-values, or a stated statistical model for comparing groups. The comparisons should not be reconstructed from absent group summaries.

Why can variability matter?

General statistical explanation: when observations are more variable, a group estimate is less precise unless the design and information available provide sufficient precision. Pharmacokinetic measurements may vary between participants, making a dispersion measure useful alongside a group summary. The record specifies a dispersion statistic but does not provide its value. It also does not report whether the analysis accounted for repeated concentration measurements, covariates, matching, or any other features of the design. Those analytic details cannot be inferred from the endpoint description alone.

What does non-randomized allocation imply?

In general, random allocation helps balance measured and unmeasured characteristics between treatment groups on average. Here, renal-function status defined the groups; participants were not randomly assigned to renal impairment. Matching to controls is described in Part 1, but matching variables and implementation are not reported. A group difference in exposure could therefore reflect renal status, other differences between groups, or both. The study's pharmacokinetic purpose and within-study measurements remain useful, but causal interpretation requires caution.

The record lists 43 outcome measures and 12 analyses. These counts do not identify which statistical procedures were used for each outcome or how results were selected and reported. A detailed statistical analysis plan, handling of multiplicity, missing-data procedures, and sample-size justification are not reported in the registry record. The sample-size illustrations associated with the posted material are planning illustrations based on an observed effect, not observed power; no such illustration should be read as a trial result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 43 outcome measures and 12 analyses. It does not report how the analyses were grouped, which outcomes were treated as confirmatory, whether statistical testing was planned across multiple endpoints or comparisons, or whether any multiplicity adjustment was used. Without those details, the risk of false-positive findings across a collection of tests cannot be evaluated. In general, multiplicity methods control or describe the consequences of drawing conclusions from several statistical tests; they do not replace reporting the estimates and uncertainty for each relevant comparison.

The primary endpoint is specified as Part 1 AUC[0-inf]. Its analysis population is described as participants in the PK Parameter Population with valid and evaluable PK parameters, drawn from the PK Population of participants who received at least one dose and had evaluable PK data. The registry record does not report how many participants contributed to the primary endpoint, how many measurements or parameters were unevaluable, or why any data were absent.

Missing-data handling is not reported in the registry record. In general, missing concentration measurements or an unevaluable pharmacokinetic profile can affect which participants contribute to an analysis and may affect how representative the analyzed group is. The record does not specify imputation, sensitivity analyses, exclusions beyond the population description, or methods for addressing missingness. It also does not report the analysis population for each of the 12 analyses in sufficient detail to assess consistency across outcomes.

These omissions limit reproducibility and make it difficult to determine how robust the reported analyses would be to alternate assumptions. The primary numerical AUC results themselves are not reported in the registry record, so neither multiplicity handling nor missing-data sensitivity can be judged from the available endpoint description.

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.

Most frequent non-serious adverse event terms

The safety listings show no serious adverse events in the listed groups: Normal, Part 1; Moderate, Part 1; Severe/ESRD Not on Hemodialysis, Part 1; ESRD on Hemodialysis (Before Hemodialysis); and ESRD on Hemodialysis (After Hemodialysis). Each listing reports 8 participants at risk and 0 participants with serious adverse events. The listings also report deaths as 0 in each group.

For other adverse events, the registry lists 0 participants in the Normal, Part 1 group, 4 in Moderate, Part 1, 4 in Severe/ESRD Not on Hemodialysis, 4 in ESRD on Hemodialysis (Before Hemodialysis), and 3 in ESRD on Hemodialysis (After Hemodialysis). These are separate group entries; the record does not explain how the before- and after-hemodialysis entries relate to participant-level counting. They should not be added together to infer a unique participant count.

In general, a zero count means no event was recorded in that listed group during the reported observation, not that the possibility of an event is ruled out. The safety counts are descriptive and do not establish a comparative safety effect, particularly in a non-randomized study. The registry record does not provide further detail about event severity apart from the serious-event classification, event timing, or causal attribution for these counts.

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

This study was designed to characterize gepotidacin pharmacokinetics across renal-function groups after a single intravenous dose. Its primary endpoint, AUC[0-inf], is a measure of plasma exposure, and the registry record specifies geometric summaries for that endpoint. This makes the study relevant to a pharmacokinetic question about whether renal impairment is associated with altered exposure.

The available record does not report numerical AUC results or group comparisons. It therefore does not establish the size, direction, or precision of any exposure difference. It cannot show from the posted results whether exposure was higher, lower, or similar in any renal-function group. Nor can it support a conclusion about whether dosing should be changed. The stated study objective was to inform whether renal-impairment dosing recommendations might be required; an objective is not itself a result or recommendation.

The study is not a randomized comparison. Renal status defined group membership, and the record describes matched controls for Part 1 without giving the matching method. Differences between groups could reflect renal function or other characteristics. The open-label design is less central to laboratory concentration measurement than to subjective outcomes, but it remains part of the study context. The primary endpoint also concerns pharmacokinetics, not bacterial infection outcomes or clinical effectiveness.

The safety listings record no serious adverse events or deaths in the listed groups, and they report other adverse-event counts. These descriptive data do not establish that events cannot occur, and they do not by themselves provide a controlled comparison of risk. The endpoint results, observation details, and broader statistical analysis are not reported in the registry record. The most defensible reading is therefore limited to the study's design, stated measurement, population definition, and recorded safety counts—not an unreported pharmacokinetic or clinical conclusion.

13. Why This Trial Matters Statistically

Renal function can be relevant to how a drug is handled by the body, making pharmacokinetic comparisons across renal-function categories important during drug development. This study was structured to measure gepotidacin plasma exposure after the same stated single dose in groups with differing renal status. AUC[0-inf] is a useful summary for that purpose because it integrates concentration information over time rather than relying on one sampling point.

The statistical interest is not only whether group summaries differ, but also how large and precise any difference is and how much participants vary within each group. Geometric summaries and a geometric coefficient of variation are appropriate descriptive tools for positive exposure measurements when proportional variation is relevant. However, the registry record does not report their numerical values or the estimated group contrasts. The intended scientific question is clear, but its quantitative answer cannot be assessed from the listed results.

The design also illustrates an important distinction: a pharmacokinetic study can compare groups defined by a biological characteristic without randomizing that characteristic. Matching to normal-function controls may support comparability, but the matching details are not reported. Interpretation therefore depends on transparent group definitions and methods as well as on endpoint estimates. The non-randomized, open-label structure should remain visible when considering claims about renal status.

Finally, the record shows why statistical reporting is essential. An endpoint definition and a completed-study status do not communicate the result on their own. Numerical estimates, uncertainty, analysis populations, missing-data handling, and multiplicity procedures would be needed to evaluate the strength and robustness of the comparison. The record establishes a relevant question and a measurement framework, while leaving those quantitative aspects unreported.

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 primary limitation for interpreting the pharmacokinetic question is that numerical AUC[0-inf] results are not reported in the registry record. Group estimates, dispersion values, contrasts, and uncertainty are therefore unavailable for assessing the magnitude or precision of exposure differences.

The study was non-randomized and open-label. Renal-function groups were not randomly assigned, and the record's description of matched controls does not identify matching variables or procedures. This prevents assessment of how closely the groups were comparable beyond renal status. The registry record also does not report adjustment methods for possible group differences.

The primary endpoint is specified for Part 1, while Part 2 was optional and included additional renal-function categories. The record does not give detailed analytic results by part or explain how the optional part affected the overall reporting. The primary analysis population is defined by receipt of at least one dose and evaluable PK data, but the number included in the endpoint analysis and reasons for unevaluable data are not reported.

Other relevant details are absent: criteria defining renal impairment, the matching procedure, the statistical model for group comparisons, missing-data methods, multiplicity handling, and sample-size justification are not reported in the registry record. The hemodialysis group description is incomplete, so its full dosing schedule cannot be assessed from the record. These limitations constrain interpretation of design and analysis; they do not establish that any particular bias or error occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetic Study of Gepotidacin in Subjects With Varying Degrees of Renal Impairment and in Subjects With Normal Renal Function — NCT02729038.
• Registry record last updated 2020-07-21; status last verified 2020-07.
• Results first posted 2018-11-20.
• 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

The registry record describes NCT02729038, a completed Phase I, open-label, non-randomized, parallel-group, multi-center study of gepotidacin in adults with varying renal function. Recorded enrollment was 32. The study start was 2016-06-29, and primary completion was 2017-06-20.

Participants received a single 750 mg dose by 2 hour intravenous infusion, with the study comparing pharmacokinetics across renal-function groups. The Part 1 primary endpoint was plasma AUC[0-inf], summarized by geometric mean and geometric coefficient of variation. The record defines a PK Parameter Population based on receipt of at least one dose and valid, evaluable PK parameters.

Numerical primary endpoint results and detailed statistical procedures are not reported in the registry record. Safety listings report no serious adverse events or deaths in the listed groups, alongside counts for other adverse events. The recorded details describe the study question and design but do not quantify the primary pharmacokinetic comparison.