GSK2251052 in the Treatment of Complicated Intra-abdominal Infections: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for GSK2251052 in the Treatment of Complicated Intra-abdominal Infections (NCT01381562), a randomized phase 2 study. The primary outcome is Number of Participants With Any Adverse Event.

2. Clinical Question

In practical terms, the central question recorded for the primary outcome was how many treated participants experienced an adverse event during follow-up, not whether a particular symptom improved. The definition included any untoward medical occurrence temporally associated with study medication, whether or not it was considered related to that medication. The record separately describes serious adverse events using criteria that include death, life-threatening events, hospitalization or its prolongation, significant incapacity, and certain other important medical events.

The trial also listed clinical, microbiological, and therapeutic response outcomes, along with maximum plasma concentration of GSK2251052. Those outcomes address different aspects of treatment evaluation, but their titles alone do not establish the results. The posted information does not give a single efficacy estimate or treatment contrast to answer whether one group had better clinical or microbiological outcomes.

3. Trial Design

This was a phase 2, randomized, triple-masked, parallel-group study of GSK2251052 for complicated intra-abdominal infection in adults. The registry records enrollment of 15 and a terminated status. The listed start date is 2011-10-03, and the primary completion date is 2012-03-05. The reason for termination is not reported in the registry record.

Three treatment groups are described. One received GSK2251052 750 mg by intravenous infusion every 12 hours with saline placebo; another received GSK2251052 1500 mg on the same schedule with saline placebo. The comparator group received meropenem 1 g by intravenous infusion every 8 hours with saline placebo. The record labels the study randomized and triple-masked, but the identities of the parties masked are not reported in the registry record.

The brief summary says that the study was intended to evaluate safety, efficacy, and pharmacokinetics/pharmacodynamics, comparing GSK2251052 with meropenem. It notes that GSK2251052 had microbiological activity that included pathogens responsible for complicated intra-abdominal infection. This is the study rationale recorded in the brief summary, not evidence of clinical benefit.

The primary outcome was the number of participants with any adverse event, with a timeframe up to Day 42. Secondary outcomes included clinical response at the test-of-cure visit 5-9 days after therapy, microbiological response, therapeutic response, and maximum plasma concentration. Several outcomes name different analysis populations, including the microbiologically evaluable and MITT populations. Their definitions, beyond the stated safety-population definition, 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 15 participants were enrolled in the study; of those, 5 participants each were randomised to receive GSK2251052, 750 milligram (mg) or 1500 mg or meropenem 1.0 gram (g), intravenously. One participant in the GSK2251052 1500 mg group was randomised but not treated, thus safety and efficacy populations consisted of 14 participants.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population comprised of all 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Any Adverse Event, measured over Up to Day 42.

The primary endpoint counts participants with any adverse event through Day 42. An adverse event was defined as an untoward medical occurrence temporally associated with use of a medicinal product, regardless of whether it was considered related to the product. The outcome is therefore a safety measure, not a direct measure of infection response or drug effectiveness.

Counting participants with an event is a binary-outcome approach at the individual level: each participant is classified according to whether the event criterion was met. The count can communicate how many participants in a group had at least one event, but a count alone does not describe event severity, duration, clinical importance, or whether multiple events occurred in the same participant. The registry separately distinguishes serious adverse events from other adverse events in the posted safety figures.

This type of endpoint is used to monitor the occurrence of unwanted medical events during treatment and follow-up. The serious-event definition in the record includes death, life-threatening events, hospitalization or prolongation of hospitalization, persistent or significant incapacity, congenital anomaly or birth defect, and certain important events requiring medical judgment. The registry describes the primary endpoint as a count of participants, but its record does not reduce the outcome, which has several categories or time points, to one treatment comparison. As a result, the posted information does not give one summary estimate of the primary endpoint’s difference between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

For a binary outcome such as whether a participant experienced an adverse event, each participant is classified as having met or not met the event definition. The registry’s primary outcome is expressed as a count of participants with any adverse event. A count describes the observed number meeting the definition; it does not, by itself, quantify the uncertainty around the underlying event frequency or the difference between groups.

General statistical explanation: a confidence interval is a range of values compatible with the observed data under a specified method. It communicates uncertainty in an estimate and is especially important when sample sizes are small. No confidence interval for a primary treatment comparison is reported in the registry record, so the precision of such a comparison cannot be assessed from a posted interval.

Why separate serious from other adverse events?

The registry reports serious adverse events separately from other adverse events. Seriousness is defined by consequences such as death, life-threatening events, hospitalization, significant incapacity, or other important medical events judged to require intervention. This classification is not the same as whether an event was caused by study medication: the primary adverse-event definition includes events regardless of whether they were considered related to the medicinal product. Readers should therefore distinguish event classification from causal attribution.

General statistical explanation: adverse-event data can include multiple events for one participant. A count of participants affected is not the same as a count of all event occurrences, and separate categories may overlap within a participant. For that reason, group-specific serious and other event counts should not be added to form an overall participant count unless the record establishes that the categories are mutually exclusive and gives the needed outcome definition. No such combined total is reported.

What can randomization and masking contribute?

The study is described as randomized, triple-masked, and parallel-group. In general, random assignment is intended to reduce systematic differences between treatment groups at allocation, while masking can reduce some forms of influence on treatment delivery or outcome assessment. These design features do not guarantee that groups will be balanced in a small trial, and they do not make descriptive counts conclusive. The registry record does not state who was masked, how randomization was implemented, or whether any departures from the assigned treatment occurred.

What does the analysis record show?

The registry record lists 23 outcome measures and 0 analyses. The primary outcome has not been reduced to a single comparison because it has several categories or time points. No treatment-effect estimate or inferential test for that primary endpoint is listed. The statistical analysis plan, any adjustment for baseline factors, and any interim analysis are not reported in the registry record. Without those details or a reported comparison, a reader cannot determine which analysis was intended to support a primary efficacy or safety claim.

How should planning calculations be read?

The stated planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the stated convention is participants per arm; time-to-event calculations use a total number of events. Such planning calculations are not observed power and do not describe the precision actually achieved in this trial. The trial’s own sample-size justification and planning rationale are not reported in the registry record.

General statistical explanation: a sample-size calculation asks how much information a future design might need under specified assumptions. It is not a measure of whether the completed study has proved an effect. An illustration based on an observed effect also depends on that effect estimate, which can be unstable when data are sparse. The record does not provide a primary treatment contrast here, so the stated assumptions should not be mistaken for evidence about efficacy or safety.

Why might sparse data make interpretation difficult?

General statistical explanation: when event counts are small, estimates can be imprecise, and conventional approximations may be less reliable than in larger samples. Exact methods or other approaches may sometimes be considered for sparse binary data, but the analysis method used for the posted adverse-event counts is not reported in the registry record. No p-value or interval should be inferred from the raw counts alone. The absence of a reported comparison does not establish that groups were equivalent; it means the record does not supply an inferential result with which to assess a difference.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 23 outcome measures, including multiple clinical, microbiological, and therapeutic response outcomes in different populations, as well as a pharmacokinetic measure. Examining multiple outcomes or several time points can increase the chance of a seemingly notable result occurring by chance if analyses are selected or interpreted without accounting for multiplicity. Whether and how multiplicity was addressed is not reported in the registry record. The primary endpoint itself is not reduced to one comparison because it has several categories or time points.

The record lists 0 analyses. No primary treatment contrast, p-value, confidence interval, or stated hierarchy among outcomes is reported. An analysis plan specifying which outcome and population would provide the principal test is not reported in the registry record. Consequently, the listed outcomes should not be treated as a set of confirmed findings, and no unreported statistical adjustment should be assumed.

Several secondary outcomes refer to the MITT population and the microbiologically evaluable population. The definitions of those populations, and the rules for deciding whether a participant was evaluable, are not reported in the registry record. The safety population is defined as participants who received at least one dose. The available record does not describe how missing outcome data were handled, whether participants were excluded from particular analyses, or how incomplete follow-up was addressed. These omissions matter because the interpretation of response outcomes can depend on population definitions and missing-data handling.

General statistical explanation: missing outcomes can affect estimated response if the probability of missingness is related to treatment or outcome. Different analysis populations can also answer different questions. Without definitions and prespecified analysis details, the robustness of any treatment comparison cannot be evaluated. The registry record’s lack of a reported analysis is not evidence that missing data or multiplicity had no effect; those methods are simply not reported.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal abscess (50.0%), blood creatinine increased (25.0%), bile duct stone (25.0%), pelvic abscess (20.0%), haemoglobin decreased (20.0%).

The safety figures count participants with serious adverse events and participants with other adverse events separately. In the GSK2251052 750 mg group, serious events affected 2 of 5 participants at risk, and other events affected 4 of 5. In the GSK2251052 1500 mg group, serious events affected 3 of 4 participants at risk, and other events affected 4 of 4. In the meropenem 1 g group, serious events affected 0 of 5 participants at risk, and other events affected 3 of 5. The registry records 0 deaths in each group.

These counts are descriptive and come from groups with few participants. They do not establish that a treatment caused an event, and they should not be interpreted as precise estimates of risk in a broader population. The primary endpoint includes events whether or not they were considered related to study medication. Seriousness is classified using the registry’s stated criteria, which include outcomes such as hospitalization and life-threatening events.

The serious-event terms and percentages are listed without a treatment-group breakdown in the available record: Abdominal abscess, 50.0%; Blood creatinine increased, 25.0%; Bile duct stone, 25.0%; Pelvic abscess, 20.0%; Haemoglobin decreased, 20.0%; and Pancreatitis acute, 20.0%. Their denominators are not reported in the registry record. They therefore cannot be used as group-specific rates or directly compared with the arm counts.

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

The registry record describes a randomized, triple-masked phase 2 study of two GSK2251052 regimens and meropenem in adults with complicated intra-abdominal infection. It records an enrollment of 15, a terminated status, and descriptive adverse-event counts through the safety reporting framework. Those counts document events observed in the trial groups, including serious and other adverse events, and no deaths are recorded in the groups.

The record does not provide a single analysis of the primary endpoint, which is the number of participants with any adverse event through Day 42. It also does not list a treatment-effect estimate, confidence interval, or p-value for a primary comparison. As a result, the counts do not establish whether the groups differed in the primary outcome, how precisely a difference might be estimated, or whether any difference would be attributable to treatment.

The trial’s listed secondary outcomes include clinical, microbiological, and therapeutic responses, as well as maximum plasma concentration of GSK2251052. Outcome names indicate what was intended for evaluation, not the observed findings. Their results and analyses are not reported in the registry record. The study’s stated interest in preliminary efficacy and pharmacokinetics/pharmacodynamics likewise does not itself show an efficacy or exposure result.

General statistical explanation: a small study can provide descriptive information while leaving substantial uncertainty about treatment differences. A non-significant result, if one were reported, would not necessarily establish equivalence; in this record, even a primary inferential result is not listed. Conversely, the presence of adverse events does not alone demonstrate a causal relationship to a study drug. The appropriate conclusion is limited to what is recorded: a terminated phase 2 trial with posted safety counts and no reported single primary comparison or secondary outcome analysis.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between recording outcomes and reporting an interpretable treatment comparison. The registry identifies a primary safety outcome and gives group-specific counts for serious and other adverse events, but the primary endpoint is not reduced to one comparison. Without an estimate and its uncertainty, readers cannot judge the precision of a between-group difference from the registry record.

The number of participants enrolled was 15, and the group counts are small. In general, sparse data make estimates sensitive to individual observations and limit the strength of conclusions that can be drawn from descriptive patterns. The counts are useful as a record of observed events, but they should not be mistaken for a definitive safety ranking or a reliable estimate of event frequency beyond the trial.

The trial also lists many different outcome measures, including response outcomes in distinct analysis populations. This makes clear why analysis plans, population definitions, missing-data procedures, and multiplicity handling are important to interpretation. Those details are not reported in the registry record, and the record lists 0 analyses. Thus the listed outcome titles cannot be treated as statistical findings.

Finally, the terminated status and the absence of a reported rationale underscore the importance of distinguishing a study’s intended questions from the conclusions its available results can support. The registry record documents a randomized and masked design, treatment regimens, outcome definitions, and safety observations. It does not establish a comparative efficacy result or resolve whether the observed safety counts reflect treatment effects. That boundary between description and inference is the central statistical lesson.

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 enrollment was 15, and the observed treatment-group counts are small. This limits the ability to assess the precision of event-frequency estimates and makes descriptive patterns vulnerable to changes in individual outcomes. The registry record does not report a confidence interval or an inferential comparison for the primary endpoint.

The study is marked terminated, but the reason for termination is not reported in the registry record. The record does not describe whether enrollment ended as planned, whether follow-up was complete, or whether any protocol changes occurred. These details could affect how results are interpreted, but no explanation should be inferred from the status alone.

The primary outcome is described as the number of participants with any adverse event through Day 42, while the registry indicates that it has several categories or time points and is not reduced to one comparison. Group-specific serious and other adverse-event counts are available, but those categories should not be combined without a stated rule. The serious-event terms and percentages are not accompanied by treatment-group breakdowns or denominators in the record available for this analysis.

Although clinical, microbiological, and therapeutic response outcomes are listed, their results and analyses are not reported in the registry record. Definitions of the MITT and microbiologically evaluable populations are not reported, and the approach to missing data is also not reported. The statistical analysis plan, multiplicity procedures, and sample-size justification are not reported in the registry record. These limitations prevent a full assessment of the intended comparisons and the robustness of any treatment conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: GSK2251052 in the Treatment of Complicated Intra-abdominal Infections — NCT01381562.
• Registry record last updated 2017-11-29; status last verified 2017-10.
• Results first posted 2017-11-29.
• 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 describes a terminated phase 2 randomized, triple-masked, parallel-group study of GSK2251052 for complicated intra-abdominal infection in adults. Enrollment was 15. The listed dates are 2011-10-03 for study start and 2012-03-05 for primary completion.

The treatment groups were GSK2251052 750 mg or 1500 mg by intravenous infusion every 12 hours, each with saline placebo, and meropenem 1 g by intravenous infusion every 8 hours with saline placebo. The primary outcome was the number of participants with any adverse event through Day 42 among the safety population, defined as participants who received at least one dose.

The record gives serious and other adverse-event counts by group and records no deaths in any group. It lists 23 outcome measures and 0 analyses. A single primary comparison, efficacy results, the termination rationale, and key analysis details are not reported in the registry record.