This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Dose-Ranging Study of GSK2140944 in the Treatment of Subjects With Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections (NCT02045797), a randomized phase 2 study. The primary outcome is Number of Participants With Composite of the Cure Rate as Measured by Clinical Response and Outcome at the Early Efficacy Visit Combined With Withdrawal Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02045797 |
| Phase | Phase 2 |
| Condition | Infections, Bacterial |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 126 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Adults with suspected or confirmed Gram-positive acute bacterial skin and skin structure infections who required in-patient medical care were the intended population. The modified intent-to-treat population included randomized participants who received at least one dose of study medication.
Intervention
Participants received one of three GSK2140944 regimens: 750 mg intravenously every 12 hours; 1000 mg intravenously every 12 hours; or 1000 mg intravenously every 8 hours. Treatment began with intravenous dosing, with a possible switch to oral dosing at the investigator’s decision.
Comparator
The three dose schedules served as parallel treatment groups. The registry record does not describe a placebo or an active comparator outside these GSK2140944 regimens.
Primary question
The primary endpoint combined clinical response at the early efficacy visit with withdrawal from study treatment due to a drug-related adverse event. It was intended to assess early lesion improvement alongside treatment withdrawal, among participants who received at least one dose.
The central statistical question is how the three dosing schedules compare on this composite endpoint. The registry record describes the endpoint but does not report the outcome counts or a statistical comparison between groups. Therefore, the record does not establish which regimen had a more favorable observed endpoint result, nor how precisely any between-group difference was estimated.
The study was designed to support dose selection by characterizing safety, tolerability, pharmacokinetics, and efficacy. That purpose is broader than testing one treatment against no treatment. The clinical question concerns evidence across several regimens within the same drug program, and the early composite incorporates both an improvement criterion and a treatment-discontinuation criterion. Those components capture different aspects of the treatment experience and should not be interpreted as interchangeable measures.
3. Trial Design
This was a Phase II, randomized, double-masked, parallel-group, two-part, multicenter dose-ranging study in adults. The registry record lists enrollment of 126 participants and a completed status. The recorded study start was 2014-03-24, and primary completion was 2015-06-29. The sponsor was GlaxoSmithKline.
Three treatment groups are described. Group A received GSK2140944 750 mg intravenously every 12 hours on Day 1 and Day 2. From Day 3 to Day 10, participants could switch to 1500 mg orally every 12 hours at the investigator’s decision or continue the intravenous regimen. Group B began with 1000 mg intravenously every 12 hours on Day 1 and Day 2, with a possible switch to 2000 mg orally every 12 hours or continued intravenous dosing from Day 3 to Day 10. Group C began with 1000 mg intravenously every 8 hours on Day 1 and Day 2, with a possible switch to 2000 mg orally every 8 hours or continued intravenous dosing from Day 3 to Day 10.
The registry record describes the groups as dose regimens, not as distinct drugs. The permitted oral switch depended on investigator decision, so actual treatment exposure could include a change in route. The record does not report how often participants switched, how randomization was implemented, how masking was maintained, or whether allocation was stratified. Details of the two study parts beyond the broad description are not reported in the registry record.
Enrollment gives the overall number recorded for the trial; it does not provide the group-specific numbers used for each endpoint. The primary endpoint population was the modified intent-to-treat population, defined as randomized participants who received at least one dose. The registry record does not report the numbers excluded from that population or the numbers analyzed for the primary endpoint.
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 126 participants were randomly assigned to study treatment (all randomized population). A total of 122 participants, who received study treatment, were included in the Modified Intent-to-Treat population (mITT) and safety populations. The mITT population is used in overall study numbers and demographic information.
Overall Study
| Stage | Gepotidacin 750 mg q12h | Gepotidacin 1000 mg q12h | Gepotidacin 1000 mg q8h |
|---|---|---|---|
| STARTED | 58 | 39 | 25 |
| COMPLETED | 51 | 32 | 24 |
| NOT COMPLETED | 7 | 7 | 1 |
Reasons for not completing this period:
| Reason | Gepotidacin 750 mg q12h | Gepotidacin 1000 mg q12h | Gepotidacin 1000 mg q8h |
|---|---|---|---|
| Adverse Event | 3 | 1 | 0 |
| Lack of Efficacy | 1 | 0 | 0 |
| Lost to Follow-up | 2 | 3 | 1 |
| Physician Decision | 0 | 1 | 0 |
| Withdrawal by Subject | 1 | 2 | 0 |
Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat (MITT) population consisted of all randomized participants who received at least one dose of study medication.
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: mITT population: those participants who received study treatment
| Characteristic | Unit | Gepotidacin 750 mg q12h | Gepotidacin 1000 mg q12h | Gepotidacin 1000 mg q8h | Total |
|---|---|---|---|---|---|
| Participants analysed | 58 | 39 | 25 | 122 | |
| Age, Continuous | Years | 44.3 (SD 11.35) | 44.6 (SD 10.76) | 45.8 (SD 12.64) | 44.7 (SD 11.36) |
| Sex: Female, Male: Female | Participants | 18 | 12 | 5 | 35 |
| Sex: Female, Male: Male | Participants | 40 | 27 | 20 | 87 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 1 | 0 | 2 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 2 | 0 | 3 |
| Race (NIH/OMB): White | Participants | 55 | 36 | 24 | 115 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Composite of the Cure Rate as Measured by Clinical Response and Outcome at the Early Efficacy Visit Combined With Withdrawal Rate, measured over Up to Day 3.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the number of participants with a composite of clinical cure response and withdrawal rate at the early efficacy visit, through Day 3. It was assessed among participants who received at least one dose of GSK2140944. Clinical improvement was defined as a reduction in overall lesion area of >20% at the early efficacy visit. Withdrawal was defined as stopping study treatment because of a drug-related adverse event at any point during treatment.
Combining these components can give an early view of both lesion response and treatment discontinuation associated with an adverse event. This can be useful in dose-ranging work, where the aim is to characterize more than one dimension of a regimen. However, the components represent different outcomes: lesion-area change is a clinical response measure, while withdrawal captures a treatment decision attributed to an adverse event. The registry description does not report the rule used to combine the component data into the composite or how a participant meeting both conditions was handled.
The endpoint is a count-based measure, but no group counts, component-specific results, or effect estimates are reported in the registry record. Without those results, the endpoint definition alone does not show the direction or size of any treatment-group differences.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the study design and endpoint but does not report the primary endpoint results. It gives no group-specific count of participants meeting the composite endpoint, no estimate of a difference between regimens, and no confidence interval or statistical test for that comparison. Consequently, the posted record cannot support a conclusion about which dose schedule had a higher or lower composite response, or about the precision of a possible difference.
This absence matters because the endpoint includes two components that can move in different directions. A regimen could have a different pattern of early lesion improvement and treatment withdrawal than another regimen. A single composite result, even if available, would need to be interpreted with its component definitions and any component-specific results. Those component results and the combination rule are not reported in the registry record.
The study’s stated purpose was dose selection through characterization of safety, tolerability, pharmacokinetics, and efficacy. Dose-ranging evidence is typically interpreted across the pattern of outcomes among regimens rather than as a simple binary verdict. The treatment groups also differ in dosing frequency, and the protocol allowed some participants to switch from intravenous to oral treatment. The record does not report actual route changes or exposure patterns, so the treatment received after the initial dosing period cannot be described from these entries.
The enrollment of 126 is a total trial figure, not a reported denominator for each outcome. The modified intent-to-treat definition identifies who was eligible for the primary analysis, but the registry record does not state how many participants met that definition or how many contributed endpoint data. The number enrolled should therefore not be treated as the number with observed primary outcomes.
The safety entries are descriptive counts. They include serious adverse events, other adverse events, deaths, and selected serious-event terms by listed treatment group. They do not provide a statistical comparison or establish that a particular event was caused by treatment. These data can be read as the reported safety experience in each group, but they do not replace the missing primary efficacy results or provide a complete assessment of benefits and harms.
The record does not report a statistical analysis plan, model for the primary endpoint, hypothesis tests, or confidence intervals. It also does not report the study’s sample-size justification. The planned dose-ranging purpose and the completed status do not, by themselves, establish that the study found a preferred dose. Any interpretation of comparative efficacy or dose selection would require results not reported in the registry record.
9. Statistical Methods Explained
For a binary or count endpoint, the observed number of participants meeting a criterion is often presented alongside the number assessed. A count answers how many participants had the event; the denominator indicates the group from which that count arose. The primary endpoint is described as a count of participants, but the registry record does not report the group counts or their denominators. No group-level event rate can therefore be interpreted from the endpoint description alone.
What does a confidence interval convey?
General statistical explanation: a confidence interval describes the uncertainty around an estimated effect under a specified analysis. A narrow interval indicates greater precision than a wide interval, while both the estimate and its interval matter for interpretation. An interval that includes values representing no difference does not establish that the groups are equivalent; it indicates that the data and method do not rule out that value at the interval’s stated confidence level. The registry record does not report a confidence interval for the primary endpoint.
General statistical explanation: a p-value measures how compatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It does not measure the probability that a treatment works, nor does it give the size or clinical importance of an effect. A p-value also does not communicate precision as fully as an effect estimate with an interval. No primary-endpoint p-value is reported in the registry record.
Why does the analysis population matter?
The primary population is defined as the modified intent-to-treat population: randomized participants who received at least one dose of study medication. This definition excludes randomized participants who did not receive treatment. It differs from a population that includes every randomized participant, and it can affect how the result represents the randomized comparison. The registry record does not report the population count by group or the number with missing endpoint data, so the consequences of exclusions and missingness cannot be assessed from the entry.
General statistical explanation: missing outcome data can reduce precision and can also introduce bias if the chance that data are missing is related to the outcome or treatment experience. Analysts may use different assumptions or methods to address missingness, but those choices need to be described because they can affect estimates. The registry record does not report a missing-data method for the primary endpoint.
How should the composite be understood?
The endpoint joins clinical improvement with withdrawal due to a drug-related adverse event. A composite can summarize multiple outcomes in one measure, but its interpretation depends on how the components are combined and how often each component occurs. A count for the overall composite does not reveal the separate frequency of each component unless those results are also reported. The registry record defines clinical improvement as >20% reduction in lesion area at the early efficacy visit and defines withdrawal by reason and timing, but does not report the combination rule or component-level counts.
General statistical explanation: when an endpoint has multiple components, a difference in the composite can be driven mainly by one component. Components may also differ in importance, frequency, and susceptibility to measurement or decision-making. For this reason, component results can add context to the overall endpoint. Here, neither the primary composite results nor its component results are reported in the registry record.
What do planning assumptions mean?
The registry record states that planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. These are planning assumptions, not evidence about the observed treatment effect. Such illustrations depend on the assumed effect and statistical method; they are not observed power and should not be interpreted as a trial result. The registry record does not report the study’s own sample-size justification.
General statistical explanation: power is a design property calculated under assumptions about an effect, variability, significance level, and analysis. Once data have been collected, a post hoc power calculation based on the observed effect does not provide a substitute for an estimate and confidence interval. Planning sample sizes are illustrative and are not the number of participants who actually experienced an outcome. No numerical planning sample-size estimates are reported in the registry record.
Finally, a randomized parallel-group design can support comparisons between assigned regimens, but the interpretation still depends on the analysis method, population, outcome ascertainment, and handling of missing data. The record does not report these details sufficiently to reconstruct a statistical analysis of the primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The study includes a primary composite endpoint and numerous secondary outcomes. The listed secondary outcomes cover clinical response at several visits and microbiological response for specified pathogen groups at the early efficacy visit. The registry record lists 48 outcome measures, but it does not report a multiplicity adjustment or a hierarchy for interpreting multiple outcomes.
General statistical explanation: testing many outcomes or time points increases the chance of at least one apparently notable result arising by chance if each is considered independently. A prespecified hierarchy, adjustment procedure, or clearly exploratory interpretation can help readers understand how multiple findings were handled. The registry record does not report such a procedure. It also does not report statistical analysis results for the listed primary or secondary outcomes.
The primary population is the modified intent-to-treat population, defined as randomized participants who received at least one dose of study medication. The record does not report the population size by treatment group, the analysis population for each secondary outcome, or the number of participants with observed measurements at each visit. Although visit windows are named for secondary outcomes, missing-data counts and methods are not reported in the registry record.
General statistical explanation: conclusions can depend on how missing outcomes are handled, especially when missingness may be related to treatment response or adverse events. Complete-case analyses, imputation, and other approaches rely on different assumptions. Without a stated method and information about missingness, readers cannot determine whether the reported analysis accounts for those issues. Here, the analysis method is not reported in the registry record.
The record also does not describe interim analyses, any stopping rules, or a statistical analysis plan. These details are not inferable from the randomized design, completed status, or number of listed outcomes.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Gepotidacin 750 mg q12h | 1 | 58 | 1.7% |
| Gepotidacin 1000 mg q12h | 1 | 39 | 2.6% |
| Gepotidacin 1000 mg q8h | 0 | 25 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Gepotidacin 750 mg q12h | 0 of 58 |
| Gepotidacin 1000 mg q12h | 1 of 39 |
| Gepotidacin 1000 mg q8h | 0 of 25 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Gepotidacin 750 mg q12h | 30 of 58 |
| Gepotidacin 1000 mg q12h | 20 of 39 |
| Gepotidacin 1000 mg q8h | 14 of 25 |
Most frequent serious adverse event terms
| Event term | Organ system | Gepotidacin 750 mg q12h | Gepotidacin 1000 mg q12h | Gepotidacin 1000 mg q8h |
|---|---|---|---|---|
| Cellulitis | Infections and infestations | 1 of 58 | 0 of 39 | 0 of 25 |
| Septic shock | Infections and infestations | 0 of 58 | 1 of 39 | 0 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Gepotidacin 750 mg q12h | Gepotidacin 1000 mg q12h | Gepotidacin 1000 mg q8h |
|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 12 of 58 | 9 of 39 | 4 of 25 |
| Diarrhoea | Gastrointestinal disorders | 5 of 58 | 6 of 39 | 5 of 25 |
| Alanine aminotransferase increased | Investigations | 4 of 58 | 3 of 39 | 2 of 25 |
| Vomiting | Gastrointestinal disorders | 3 of 58 | 2 of 39 | 3 of 25 |
| Aspartate aminotransferase increased | Investigations | 3 of 58 | 3 of 39 | 1 of 25 |
| Headache | Nervous system disorders | 6 of 58 | 1 of 39 | 0 of 25 |
| Flatulence | Gastrointestinal disorders | 3 of 58 | 1 of 39 | 2 of 25 |
| Gamma-glutamyltransferase increased | Investigations | 3 of 58 | 3 of 39 | 0 of 25 |
| Infusion site extravasation | General disorders | 3 of 58 | 1 of 39 | 0 of 25 |
| Pruritus generalised | Skin and subcutaneous tissue disorders | 1 of 58 | 3 of 39 | 0 of 25 |
Serious events with the highest arm-level rate: septic shock (2.6%), cellulitis (1.7%).
The registry record reports serious adverse events, other adverse events, and deaths for three groups labelled Gepotidacin 750 mg q12h, Gepotidacin 1000 mg q12h, and Gepotidacin 1000 mg q8h. In the 750 mg q12h group, 1 participant was affected by a serious adverse event among 58 at risk, 30 were affected by other adverse events among 58 at risk, and 0 deaths were recorded. In the 1000 mg q12h group, 1 participant was affected by a serious adverse event among 39 at risk, 20 were affected by other adverse events among 39 at risk, and 1 death was recorded. In the 1000 mg q8h group, 0 participants were affected by a serious adverse event among 25 at risk, 14 were affected by other adverse events among 25 at risk, and 0 deaths were recorded.
The listed top serious-event terms are septic shock at 2.6% and cellulitis at 1.7%. The registry record does not specify the denominator or further detail for these term percentages in the listed entry. Counts describe what was recorded; they do not, on their own, establish causation or show that groups differ statistically. The record does not report an adjusted safety comparison or uncertainty intervals. These safety figures should be read as descriptive registry counts, not as a complete comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The available registry information establishes that a randomized, double-masked Phase II dose-ranging study was conducted and completed, with three GSK2140944 schedules and a primary endpoint combining early clinical improvement with treatment withdrawal due to a drug-related adverse event. It also gives the endpoint definitions, the modified intent-to-treat population definition, and descriptive adverse-event counts.
It does not establish the primary endpoint result. The registry record does not report the number of participants meeting the composite in each group, the component counts, an effect estimate, or a confidence interval. Without those results, it is not possible to describe the direction, magnitude, or precision of a comparison among the dose regimens. The endpoint definition and study purpose cannot substitute for observed outcome data.
The safety counts provide a limited descriptive account by group, but they are not a statistical test of differences and do not establish whether an event was caused by treatment. The entry also does not report details needed to assess missing data, analysis methods, or the full context of safety ascertainment. These limits mean that the posted information is insufficient for a comprehensive benefit-harm comparison.
General statistical explanation: a trial’s design describes how evidence was intended to be collected; results describe what was observed; and inference describes how uncertain a comparison remains. These are distinct. Randomization and masking are features of the design, while a comparative conclusion requires the relevant analyzed outcomes and an account of their uncertainty. For this study, key comparative outcome results are not reported in the registry record.
The absence of a reported result should not be interpreted as evidence that the groups were the same, or that one was better or worse. It means that the registry entry does not provide the information needed to answer those questions. The record also does not report whether a dose was selected for future studies, despite describing dose selection as a study objective.
13. Why This Trial Matters Statistically
This trial is statistically notable as a dose-ranging study rather than a single comparison of a treatment with placebo. It randomized participants among three schedules that differed in dose and dosing frequency, and the study description also allowed a possible change from intravenous to oral administration. Such a design can inform dose selection by examining patterns across regimens, provided outcome results and their uncertainty are available.
The primary endpoint brings together early lesion improvement and withdrawal due to a drug-related adverse event. That combination illustrates a common design choice: balancing a measure of clinical response with an aspect of treatment tolerability. It also creates an interpretive requirement. Readers need to know the composite result and the contribution of each component, because the same overall composite could reflect different underlying response and withdrawal patterns.
The entry demonstrates why trial registration details and results must be distinguished. The record describes a completed trial, its population, treatment schedules, endpoint, and selected safety counts, but does not report the primary comparative efficacy results. Completion and enrollment alone do not answer the statistical question. Nor does the stated goal of selecting an optimal dose show that a particular schedule was selected.
General statistical explanation: useful dose-ranging interpretation requires estimates that show the observed pattern and how uncertain it is, not just a list of regimens. Confidence intervals, analysis populations, missing-data handling, and multiplicity procedures can all affect how convincingly differences are characterized. Those details are not reported in the registry record for the primary endpoint.
For clinical researchers, the study is a reminder that a well-defined endpoint is only one part of an interpretable trial. Transparent results and methods are needed to connect the design to a comparative conclusion. In this entry, the available information supports a description of the trial structure and reported adverse-event counts, but not a conclusion about relative efficacy across regimens.
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 is that the registry record does not report results for the primary composite endpoint. Group-specific endpoint counts, component-specific results, effect estimates, confidence intervals, and statistical tests are not reported. This prevents assessment of the size, direction, and precision of comparisons among the treatment schedules.
The record defines a modified intent-to-treat population but does not report its size by group or the number of participants contributing primary endpoint data. It does not provide missing-data counts, a missing-data method, or details of exclusions from the analysis population. The registry record also does not report how the composite components were combined or whether separate component results were analyzed.
Details of the statistical analysis plan are not reported in the registry record. This includes the model used for the primary endpoint, any prespecified pairwise comparisons, multiplicity handling, interim analyses, and stopping rules. The record does not report a sample-size justification. Consequently, the intended statistical framework and its relation to the study’s dose-selection objective cannot be evaluated from the entry.
Although the three dosing schedules are described, actual treatment exposure after Day 2 is not reported, including how often participants changed to oral dosing. The record does not report group-specific results for the listed secondary clinical and microbiological outcomes. The adverse-event entries are descriptive and do not include an adjusted comparative analysis or uncertainty estimates.
These limitations concern what can be concluded from the registry record. They do not show that the study lacked analyses or that no results exist elsewhere; such information is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dose-Ranging Study of GSK2140944 in the Treatment of Subjects With Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections — NCT02045797.
- Registry record last updated 2017-11-17; status last verified 2017-10.
- Results first posted 2017-09-21.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT02045797 is a completed Phase II, randomized, double-masked, parallel-group, multicenter, two-part dose-ranging study in adults with suspected or confirmed Gram-positive acute bacterial skin and skin structure infections. The registry record lists 126 participants and three GSK2140944 dosing schedules, with possible intravenous-to-oral switching during treatment.
The primary endpoint was a composite involving clinical improvement at the early efficacy visit and withdrawal due to a drug-related adverse event, assessed through Day 3 in the modified intent-to-treat population. The record defines the population and endpoint components but does not report primary outcome counts or comparative analyses. It lists selected adverse-event counts and terms descriptively. Statistical analysis methods, missing-data handling, multiplicity procedures, and the study’s sample-size justification are not reported in the registry record.