To Assess Bioavailability, Food Effect and Pharmacokinetics of Gepotidacin Tablets: A Phase I, Single-Dose, 2 Part Study in Healthy Subjects.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Assess Bioavailability, Food Effect and Pharmacokinetics of Gepotidacin Tablets: A Phase I, Single-Dose, 2 Part Study in Healthy Subjects. (NCT02853435), a randomized phase 1 study. The primary outcome is Area Under the Concentration-time Curve From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of Plasma Gepotidacin for Part 1a.

2. Clinical Question

3. Trial Design

This was a Phase I, multicenter study of gepotidacin formulations and pharmacokinetics. The official title describes an open-label study in Parts 1 and 2 and a randomized, double-blind, placebo-controlled design in Part 3. The registry’s overall allocation field is randomized, masking is listed as none, and the model is crossover. The brief summary organizes the study into two parts, while the official title and arm descriptions refer to three parts; the registry record does not reconcile those descriptions.

Part 1a was a three-period crossover comparison under fasted conditions. Participants were assigned to treatment sequences involving the reference capsule, RC tablet, and HSWG tablet, with each formulation administered as a single dose. This structure allows formulation comparisons within a crossover study, but the registry record does not report the washout interval, sequence-specific results, or details of any period or sequence adjustment.

Part 1b was described as a two-period crossover assessment of food effect for the tablet formulation selected from Part 1a. Part 2 was described as evaluating the selected tablet formulation in Japanese and Chinese subjects under fasted conditions. These parts address questions distinct from the Part 1a primary endpoint. Results for their primary pharmacokinetic comparisons are not reported in the registry record.

The registry lists enrollment of 48 and a completed status. The brief summary gives approximate enrollment plans for the component parts, but the registry record does not explain how the overall enrollment figure relates to those planning figures. The study start and primary completion dates are recorded as 2016-08-04 and 2017-10-17.

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 48 participants were enrolled in the study of which 26 participants were randomized in Part 1a, 10 participants were randomized in Part 2 and 12 participants were part of Placebo-controlled Part 3.

Part 1a, Period 1 (3 Days)

Part 1a, Washout Period 1 (3 Days)

Part 1a, Period 2 (3 Days)

Part 1a, Washout Period 2 (3 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 Concentration-time Curve From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of Plasma Gepotidacin for Part 1a, measured over Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period.

The primary endpoint is the area under the plasma concentration–time curve from time 0, before dosing, extrapolated to infinite time (AUC [0-infinity]) for gepotidacin in Part 1a. It summarizes overall measured drug exposure over time, including an extrapolated contribution beyond the last measured concentration. The registry describes blood sampling from pre-dose through 48 hours and says pharmacokinetic parameters were derived from plasma concentration-time data using standard non-compartmental analysis.

Relative bioavailability compares exposure from different formulations. AUC is useful for this purpose because it condenses the concentration-time profile into a measure of total exposure, allowing the tablet formulations to be compared with the reference capsule. The registry reports geometric least-squares means and ratios of those means. These are pharmacokinetic summaries; they do not directly measure symptoms, infection outcomes, or clinical benefit.

The endpoint is specified for the pharmacokinetic parameter population: participants in the pharmacokinetic population with valid and evaluable parameters. The registry reports geometric coefficient of variation as the measure of dispersion for the arm-level endpoint values. This describes variability on the geometric scale; it is not a confidence interval for a treatment comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous pharmacokinetic measure summarized on a geometric scale. Plasma concentrations were collected over time, and AUC [0-infinity] was estimated from the concentration-time data. The registry states that standard non-compartmental analysis was used and identifies Phoenix WinNonlin Version 6.2.1 or higher. Non-compartmental analysis estimates pharmacokinetic quantities from observed concentrations and sampling times without requiring the concentration-time course to follow a specified compartment model. The registry does not provide the detailed calculation settings or explain how the extrapolated portion of AUC was handled for individual participants.

Why use geometric means?

Pharmacokinetic measurements are often analyzed on a logarithmic scale because exposure values can be right-skewed and treatment effects are commonly expressed as relative changes. A geometric mean summarizes the central value on that scale and, when compared between formulations, naturally supports a ratio. The registry reports geometric least-squares means, which generally represent model-based means on the log scale transformed back to the original scale. The specific model used for these least-squares means is not reported in the registry record, so its adjustment terms cannot be described.

What does the ratio express?

A ratio of geometric means compares exposure between formulations multiplicatively. A ratio of 1 corresponds to equal geometric means; values on either side indicate relative differences according to which formulation is in the numerator. The registry lists a ratio and confidence interval for each tablet-versus-capsule comparison, but does not provide a plain-language statement of ratio direction. Accordingly, the numerical comparisons can be reported as recorded without assigning a numerator not explicitly described in the record.

How should the confidence intervals be read?

As a general explanation, a confidence interval reflects sampling uncertainty under the statistical model and its assumptions. A wider interval indicates less precision than a narrower interval on the same scale. The registry reports 90% confidence intervals for the two ratios. These intervals do not capture every source of uncertainty: for example, they do not by themselves account for uncertainty about model choice, unreported design details, or the applicability of results to other populations. No formal equivalence bounds or other decision thresholds are reported in the registry record. Therefore, whether an interval meets a particular regulatory or scientific criterion cannot be determined from these results alone.

Why does the crossover design matter?

In a crossover study, participants receive more than one treatment across periods. Comparing treatments within participants can reduce the influence of stable differences between participants, because each person can contribute information under multiple conditions. The design also makes period effects, treatment sequence, and possible carryover relevant. The arm descriptions identify three treatment sequences in Part 1a, but the registry does not report the washout duration or the analysis terms used to account for period and sequence. It is therefore not possible to assess those design features from the posted summary alone.

What does the coefficient of variation describe?

The arm-level geometric coefficients of variation are 25.7 for capsules, 23.0 for RC tablets, and 24.0 for HSWG tablets. As a general explanation, a coefficient of variation describes relative dispersion rather than uncertainty around a comparison. It should not be substituted for the confidence interval of a ratio. The registry does not report individual-level distributions or additional diagnostic information that would show how the variability was assessed.

What is not established by these methods?

The methods and results concern pharmacokinetic exposure after a single dose. They do not establish clinical efficacy, safety across broader use, or the performance of the formulations in people with bacterial infections. Although the study includes secondary safety outcomes and later study parts, their presence does not change the interpretation of this primary Part 1a endpoint. The registry record does not report the detailed statistical analysis plan, missing-data procedures, multiplicity adjustment, or prespecified criteria for selecting a formulation.

10. Analyses Reported by the Sponsor

The registry reports sponsor analyses as ratios of geometric least-squares means with 90% confidence intervals. Those analyses are the primary posted inferential results for the Part 1a formulation comparisons: 1.042 with an interval from 0.981 to 1.106 for the capsule and RC tablet comparison, and 1.111 with an interval from 1.046 to 1.180 for the capsule and HSWG tablet comparison. P-values are not reported for these comparisons.

A recalculated estimate is not reported in the registry record, so there is no recalculation to compare numerically with the sponsor’s analysis. The arm-level geometric means and variability values do not, by themselves, reproduce a crossover analysis; participant-level paired data and details of the fitted model would be needed to evaluate an independent reanalysis. The registry record does not provide those data or sufficient model details.

The sponsor’s reported confidence intervals should therefore be read as the available inferential results, while recognizing the limits of the information accompanying them. No discrepancy between sponsor and recalculated results is identified in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 111 outcome measures and 65 posted secondary outcomes. The primary endpoint is the Part 1a AUC [0-infinity] comparison across formulations. The record also lists numerous safety and laboratory outcomes, and describes distinct questions in the food-effect and Japanese and Chinese study components. Testing many outcomes or comparisons can increase the chance that some results appear noteworthy by chance, particularly when no adjustment or prespecified hierarchy is used.

The multiplicity strategy is not reported in the registry record. It does not say whether the Part 1a comparisons were designated as co-primary or ordered, whether any formal adjustment was applied, or how the many secondary outcomes were handled. The reported 90% confidence intervals should therefore be interpreted as the intervals presented, without assuming that they account for multiple comparisons. The record also does not state the prespecified thresholds that would guide formulation selection.

Missing-data procedures are not reported in the registry record. The primary endpoint population is described as participants with valid and evaluable pharmacokinetic parameters, but the record does not give the number excluded from that population, reasons for missing or unevaluable data, or any imputation approach. It also does not report sensitivity analyses addressing missing pharmacokinetic measurements.

The registry identifies a pharmacokinetic parameter population, but does not provide a full description of the analysis populations for each part or each outcome. The outcome description indicates that the endpoint statistics are geometric least-squares means and that valid, evaluable pharmacokinetic parameters were required. Further details about protocol deviations, exclusions, or how participants were handled across crossover periods are not reported in the registry record. These omissions limit assessment of whether the analysis population and methods were fully aligned with the planned study design.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events in the listed groups. For the three Part 1a formulation groups, the listed numbers at risk are 26 for capsules, 26 for RC tablets, and 26 for HSWG tablets; the number with a serious adverse event is 0 in each. The record also lists 0 deaths in each of these groups. These are event counts over the reported study period, not estimates of comparative risk.

The registry separately lists non-serious adverse events in the same groups: 8 for capsules, 5 for RC tablets, and 9 for HSWG tablets. Other listed groups include additional doses, fed conditions, and placebo, with their own numbers at risk and non-serious event counts. Those groups reflect other study components and should not be combined with the Part 1a formulation comparison as though they were one randomized contrast.

As a general statistical caution, zero observed serious events does not prove that the risk is zero. Small study groups and limited follow-up can leave uncommon or delayed events unobserved. The registry record does not provide event-level descriptions for the serious-event summary, nor does it establish that these short-term, single-dose findings characterize safety in other populations or treatment settings.

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

The posted primary results describe plasma gepotidacin exposure after a single dose of three formulations in the Part 1a fasted-condition comparison. The geometric mean AUC values and the two reported ratios provide a pharmacokinetic comparison of the tablet formulations with the reference capsule. The confidence intervals convey uncertainty around those reported ratios, subject to the analysis assumptions and the limitations of the registry’s methodological detail.

These findings do not answer whether gepotidacin prevents or treats bacterial infections, or whether one formulation produces better clinical outcomes. The study enrolled healthy subjects and the primary endpoint measures drug exposure rather than infection response. The findings also do not establish that the formulations are interchangeable: the registry does not provide prespecified equivalence limits or a formal equivalence conclusion.

The results do not establish the effect of food or pharmacokinetics in Japanese or Chinese subjects. Those questions are described in later study components, but their relevant outcome results are not reported in the registry record. Nor do the single-dose data characterize repeated dosing, long-term safety, or outcomes in patients.

The reported absence of serious adverse events in the listed groups is a description of observed events, not proof that serious harms cannot occur. Likewise, the non-serious event counts should be interpreted in the context of the small groups, the study’s short single-dose setting, and the different study components. The registry does not report enough detail to make broader safety comparisons.

Overall, the record supports a limited interpretation: it documents relative pharmacokinetic measurements and short-term adverse-event counts for the study populations and conditions described. Broader conclusions require evidence beyond these posted results.

14. Why This Trial Matters Statistically

This trial illustrates how early-phase formulation research can be framed around pharmacokinetic exposure rather than clinical outcomes. Before a formulation is evaluated in later research, relative bioavailability can help characterize whether different manufacturing approaches produce different measured exposure after dosing. The crossover design is pertinent because it permits comparisons across formulations within treatment sequences, while also making period and sequence considerations important to the analysis.

The record also shows why a point estimate should not be read alone. The ratios are accompanied by 90% confidence intervals, which communicate uncertainty in the comparison. At the same time, the absence of reported equivalence criteria, p-values, and detailed model specifications limits what can be concluded from those intervals. The arm-level means and variability summaries add descriptive context but do not replace the comparative analysis.

Another statistical lesson is the distinction between an endpoint’s intended role and its clinical meaning. AUC [0-infinity] is a measure of drug exposure, not a patient outcome. The Part 1a results therefore address relative pharmacokinetics in healthy subjects, while the food-effect and ethnicity-related questions belong to separate components and require their own outcome results.

Finally, the record highlights the value of transparent reporting. Clear definitions of analysis populations, missing-data handling, multiplicity strategy, model terms, and decision thresholds would help readers assess precision and interpret comparisons. Their absence does not erase the reported estimates, but it narrows the conclusions that can responsibly be drawn from them.

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 primary endpoint results apply to the Part 1a pharmacokinetic parameter population, not necessarily every enrolled subject. The registry does not report how many participants had valid and evaluable parameters for each treatment, why any data were unavailable, or whether missing observations affected the comparisons.

Although the study is described as a crossover, the registry does not report the washout interval, the model terms used for period or sequence, or an assessment of carryover. It also does not provide enough detail to reproduce the geometric least-squares mean estimates. The confidence intervals and ratios are therefore best treated as the sponsor’s reported analyses rather than independently verifiable estimates.

The record does not specify multiplicity adjustment, prespecified decision thresholds, or criteria for selecting the formulation for later study. This matters because the registry describes numerous outcomes and several distinct study questions. The primary results alone cannot show how the sponsor’s formulation decision was made.

The registry’s descriptions of study structure are not fully aligned: the official title refers to three parts, while the brief summary describes two parts. The record does not explain this difference. The overall enrollment listing is also not reconciled with the approximate enrollment figures in the brief summary.

Finally, this is a single-dose study in healthy subjects. Its primary outcome is pharmacokinetic exposure, and the record does not provide the reported results for the food-effect and Japanese and Chinese pharmacokinetic questions. These features limit generalization to patients, repeated dosing, other populations, and clinical outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: To Assess Bioavailability, Food Effect and Pharmacokinetics of Gepotidacin Tablets: A Phase I, Single-Dose, 2 Part Study in Healthy Subjects. — NCT02853435.
• Registry record last updated 2020-10-08; status last verified 2020-09.
• Results first posted 2018-11-14.
• 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 describes a completed Phase I study of gepotidacin formulation bioavailability, food effect, and pharmacokinetics. The Part 1a primary endpoint is plasma AUC [0-infinity] under fasted conditions, summarized with geometric least-squares means. The posted comparisons report ratios of 1.042 and 1.111, each with a 90% confidence interval.

Part 1a used a crossover design to compare RC and HSWG tablets with a reference capsule. The registry also describes a food-effect component and pharmacokinetic evaluation in Japanese and Chinese subjects. Results for those later questions are not reported in the registry record. The primary endpoint is a measure of drug exposure in healthy subjects, not a clinical outcome. The record reports no serious adverse events in the listed groups and includes non-serious event counts, but the small, single-dose study does not establish broader safety.