Pharmacokinetics of Gepotidacin Tablets in Adults and Adolescents Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics of Gepotidacin Tablets in Adults and Adolescents Subjects (NCT04079790), a randomized phase 1 study. The primary outcome is Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This completed Phase I study is described as randomized, double-blind, sequential, and divided into two parts. Part 1 enrolled healthy adults and was planned as a 3-period fixed-sequence study. Part 2 enrolled healthy adolescents and was planned as a 2-period fixed-sequence study. The registry record reports total enrollment of 34 participants and lists the condition as bacterial infections, although participants in the study were healthy.

The main study objective was to evaluate pharmacokinetics, safety, and tolerability of gepotidacin tablets. In Part 1, the planned pharmacokinetic evaluations included a single oral 1500 mg dose and two 3000 mg doses administered 12 hours apart or 6 hours apart. In Part 2, the record describes a single oral 1500 mg dose and two 3000 mg doses 6 hours apart. Matching placebo regimens were also listed. The study summary says the adolescent dosing interval would be determined based on Part 1 pharmacokinetic and safety results; the Part 2 regimen description identifies a 6-hour interval.

The registry lists a start date of 2019-09-04, a primary completion date of 2019-11-25, and a completed status. Fixed-sequence periods are not equivalent to independent parallel groups: participants may encounter different regimens across periods. The registry’s group counts therefore should be read as regimen-specific safety counts, not assumed to represent separate, non-overlapping populations. Further details about sequence implementation and the allocation of participants across periods are not reported in the registry record.

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 34 participants were randomized in this study (Randomized Population): 16 adult participants in Part 1 and 18 adolescent participants in Part 2.

Part 1, Period 1(Day 1 to Day 4)

Reasons for not completing this period:

Part 1, Period 2 (Day 5 to Day 8)

Part 1, Period 3 (Day 9 to Day 11)

Part 2, Period 1 (Day 1 to Day 3)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PK parameter Population consisted of all participants in the PK Population (participants who received at least 1 dose of gepotidacin and had evaluable post-dose plasma concentration data for gepotidacin), for whom valid and evaluable PK parameters were derived.

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 Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Up to Day 19.

The primary endpoint is the number of Part 1 participants with non-serious adverse events and serious adverse events, assessed up to Day 19 in the Safety Population. An adverse event is defined in the record as an untoward medical occurrence temporally associated with study intervention, whether or not it is considered related to that intervention. A serious adverse event is an event meeting specified seriousness criteria, including death, a life-threatening event, inpatient hospitalization or its prolongation, persistent disability or incapacity, congenital anomaly or birth defect, or another medically important situation.

The record says that common non-serious events and serious events are presented when they affect at least 5% of participants. This endpoint is a count of participants with events, not a direct measure of drug concentration or pharmacokinetic exposure. Event counts provide a descriptive account of safety observations during the stated period. They do not, by themselves, establish that an event was caused by a study intervention or quantify a difference between regimens.

Safety and tolerability were among the stated objectives, making adverse-event monitoring relevant to the study’s evaluation of dosing regimens. The endpoint description does not report a separate formal hypothesis or statistical comparison. The record’s primary outcome is limited to Part 1, while safety counts are also listed for Part 2.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint call for descriptive interpretation rather than an assumed treatment-effect analysis. The study is described as randomized and double-blind, but it is also sequential and fixed-sequence. Randomization and masking describe features of how the study was conducted; they do not, on their own, identify the statistical model used for every outcome. The precise analysis plan, including any model for repeated observations across periods, is not reported in the registry record.

What does an event count represent?

The primary endpoint is a count of participants with adverse events, not a count of all individual episodes. A participant is counted as having an event under the relevant outcome definition; a total count of participants therefore cannot show how many separate events occurred in those participants. The registry’s safety results distinguish serious from non-serious events. They also state that commonly occurring non-serious events are reported at the threshold of at least 5%. The presented group counts should be read in that context and not as a complete account of every possible event term.

A count paired with the number of participants at risk describes what was observed in that regimen group. It is not automatically a causal contrast. A comparison between regimens would need to account for the study’s sequential structure and define the relevant participants, periods, and estimand. The registry record does not report such a comparative analysis for this endpoint.

Why do confidence intervals matter?

In general, a confidence interval describes the uncertainty around an estimated quantity under a specified statistical method. It can show how much precision the data provide, in addition to the estimate itself. No confidence intervals for the adverse-event counts or comparative effects are reported in the registry record. The observed counts therefore should not be read as precise estimates of event frequency beyond the participants and regimens listed.

In general, small groups tend to yield less precise estimates than larger groups, especially for uncommon outcomes. A zero count is still an observed count; it is not a guarantee that the underlying event rate is zero. This distinction is important for serious adverse events, for which the listed counts are zero in every displayed group.

What can a significance test establish?

A hypothesis test requires a defined comparison, an outcome model or test procedure, and a stated statistical analysis. The registry record reports zero analysis entries and does not report a statistical test for this primary endpoint. No p-value or formal comparison should therefore be inferred from the event counts. A difference between displayed counts, even when visually apparent, is not a reported test result.

Multiplicity is also relevant when a study records many outcomes or makes multiple comparisons. The registry lists 94 outcome measures, including several pharmacokinetic measures. The adjustment strategy, if any, for multiple outcomes or comparisons is not reported in the registry record. Without a stated analysis plan, the effects of multiplicity on any inferential claims cannot be assessed.

How should planning illustrations be read?

Any sample-size illustrations associated with the results are planning illustrations based on an observed effect, not the trial’s own design justification. They should not be interpreted as observed power or as proof that the study was adequately powered for a particular comparison. The assumptions described for such illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. These assumptions are not evidence that the study used that design or analysis. The trial’s sample-size justification is not reported in the registry record.

For count outcomes, general statistical methods may need to account for variation beyond what a simple model assumes. Over-dispersion is a general term for greater variability than a model expects; if present, ignoring it can make uncertainty appear too small. The registry record does not report whether over-dispersion was assessed or whether a count model was used. Given the absence of a reported comparative analysis, no model-specific interpretation is warranted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 94 outcome measures, including the primary safety outcome and multiple secondary pharmacokinetic outcomes. When many outcomes or comparisons are examined, multiplicity can increase the chance of at least one apparently unusual result arising by chance. A statistical plan may address this through a prespecified hierarchy or adjustment, but the approach used in this study is not reported in the registry record. The number of analyses listed is 0, and no inferential comparison for the primary adverse-event endpoint is reported.

Missing-data handling is also not reported in the registry record. The posted adverse-event counts do not explain whether all participants completed the relevant observation period, how incomplete follow-up was handled, or whether any participants were excluded from a specific outcome. The record identifies the Safety Population for the primary endpoint, but additional details about its definition and the handling of missing observations are not reported.

The record does not report a sample-size justification, interim analyses, or a detailed statistical analysis plan. This absence limits assessment of whether the study was designed for a particular safety comparison, how repeated periods were handled analytically, or whether decisions were made based on accumulating data. The listed sample-size illustrations are planning exercises based on an observed effect, not descriptions of the trial’s own design or evidence of observed power.

These omissions do not change the descriptive counts, but they restrict what can be concluded from them. In particular, they do not support claims about statistical significance, multiplicity-adjusted effects, or the precision of a comparison.

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 serious adverse-event count is zero in every displayed group: Part 1 placebo, gepotidacin 1500 mg, gepotidacin 3000 mg at a 12-hour interval, and gepotidacin 3000 mg at a 6-hour interval; and Part 2 placebo, gepotidacin 1500 mg, and gepotidacin 3000 mg at a 6-hour interval. The record also lists zero deaths in each group. These counts describe the observations recorded during the study; they do not show that serious events are impossible or rule out events outside the study.

Non-serious adverse-event counts vary across the regimen groups: 0 of 2, 1 of 14, 10 of 13, and 9 of 13 in Part 1, and 2 of 3, 9 of 14, and 12 of 12 in Part 2, in the order described in the statistical interpretation. The denominators are small, and the study is sequential, so these figures should not be read as a simple randomized comparison between independent groups. The record does not report a statistical test, uncertainty interval, or causal attribution for these counts. An adverse event is defined by its occurrence in temporal association with an intervention, whether or not considered related.

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

The registry supports a narrow descriptive conclusion: it records adverse-event counts for the listed adult and adolescent regimens, with no serious adverse events or deaths listed in those groups. It also records non-serious adverse events in several groups. These observations describe what was reported among the participants at risk in the listed regimens and within the study’s recorded follow-up.

They do not establish that gepotidacin caused any particular event, or that placebo caused or prevented an event. They do not quantify a comparative effect between treatment and placebo, because the registry record reports no statistical comparison for this outcome. The sequential fixed-sequence design, differences between study parts, and small group counts further limit direct comparisons between the listed regimens.

The results also do not show whether gepotidacin is effective for bacterial infections. Participants are described as healthy adults and adolescents, and the primary endpoint is an adverse-event count. Although the study’s broader objective was pharmacokinetic evaluation, the registry entries do not include numerical pharmacokinetic results. The listed urine outcomes indicate what was to be measured, not the values observed.

In general, clinical interpretation depends on the population, intervention, comparator, outcome, follow-up, and analysis. Here, the available record is most informative as a report of observed safety counts under the study regimens. It does not support a conclusion about efficacy, long-term safety, or the frequency of events in a broader population. Such conclusions would require additional reported results and an appropriate analysis.

13. Why This Trial Matters Statistically

This study illustrates a statistical distinction between a trial’s broad scientific objective and the primary endpoint displayed in its record. Its stated purpose centered on pharmacokinetics in healthy adults and adolescents, while the listed primary outcome counts adverse events in Part 1. The record also includes several urine pharmacokinetic outcomes. Keeping those outcome types separate prevents safety counts from being mistaken for measures of drug exposure.

The sequential fixed-sequence design also matters. Regimen-specific counts are not necessarily counts from independent parallel groups, and the adult and adolescent parts involve different populations and schedules. A straightforward comparison of the displayed numbers could overlook those design features. Statistical interpretation requires knowing which participants contributed to each period and how within-participant observations were handled; those analytic details are not reported in the registry record.

Small group sizes make careful language especially important. Zero serious events in the listed groups is a factual description, but it is not evidence that the underlying risk is zero. Similarly, non-serious event counts describe observations without establishing causation or a comparative treatment effect. The absence of reported confidence intervals and tests means that uncertainty around between-regimen differences cannot be quantified from the record.

Finally, the record shows why registration details and outcome results need to be read together. The number of listed outcome measures is substantial, while multiplicity handling and the statistical analysis plan are not reported. This limits how far readers can extend descriptive findings into inferential claims. The most defensible statistical reading is therefore specific: identify the population and regimen, report the observed counts, and distinguish them from causal or comparative conclusions.

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 registry record offers limited information for evaluating comparative safety. It reports counts by regimen but no inferential analysis, confidence intervals, or statistical tests for the primary endpoint. The sample-size justification, detailed analysis plan, interim analyses, and multiplicity strategy are not reported in the registry record. Missing-data procedures and details about completion of follow-up are also not reported.

The group sizes are small, and the study is sequential and fixed-sequence. As a result, regimen counts should not be treated as though they came from independent parallel groups without further design and analysis details. The record does not describe how any within-participant dependence across periods was handled. Part 1 and Part 2 also differ in age group and dosing schedule, limiting simple comparisons across parts.

The primary endpoint is limited to safety events in Part 1 through Day 19, while the record separately lists safety counts for Part 2. The record does not provide individual event terms or an account of event relatedness in the registry record for these groups. It also does not include numerical pharmacokinetic results, despite the study’s stated pharmacokinetic objectives and its listed urine outcomes. These limitations restrict interpretation to the reported counts and design features; broader safety, pharmacokinetic, or efficacy conclusions are not supported by the available information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetics of Gepotidacin Tablets in Adults and Adolescents Subjects — NCT04079790.
• Registry record last updated 2020-09-04; status last verified 2020-08.
• Results first posted 2020-09-04.
• 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

NCT04079790 is a completed Phase I, randomized, double-blind, sequential, two-part study of gepotidacin tablets in healthy adults and adolescents. The registry reports enrollment of 34 participants. Part 1 evaluated adult regimens, including a single 1500 mg dose and two 3000 mg doses at 12-hour and 6-hour intervals; Part 2 evaluated adolescent dosing, including a single 1500 mg dose and two 3000 mg doses at a 6-hour interval. Matching placebo regimens were listed.

The primary endpoint counts Part 1 participants with non-serious and serious adverse events through Day 19 in the Safety Population. No serious adverse events or deaths are listed in the regimen groups. Non-serious event counts are reported by regimen, but no comparative statistical analysis is reported. The registry also lists urine pharmacokinetic outcomes, without numerical pharmacokinetic results in the registry record described. Details on sample-size justification, missing-data handling, multiplicity, and the analysis plan are not reported in the registry record.