Retapamulin Ointment in Healthy Adults Nasally Colonized With Staphylococcus Aureus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Retapamulin Ointment in Healthy Adults Nasally Colonized With Staphylococcus Aureus (NCT00539994), a randomized phase 2 study. The primary outcome is Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing.

2. Clinical Question

The clinical question is framed around drug exposure in healthy nasal carriers, rather than treatment of a clinical infection. The registry describes safety, tolerability, pharmacokinetics, and efficacy as study aims. Its primary outcome, however, is plasma exposure after dosing. Separate secondary outcomes address nasal carriage, recolonization, pharyngeal carriage, and MRSA cultures. Those outcomes concern bacterial carriage status; they should not be conflated with the primary pharmacokinetic measure.

The study was randomized, double-blind, and placebo-controlled according to its official title and design description. The registry lists an enrollment of 57. Its brief description says approximately 57 healthy carriers would be enrolled and stratified by carrier status. The reported record does not include numerical values for the primary pharmacokinetic outcome, so it does not allow readers to assess the magnitude or precision of plasma exposure in the treatment groups.

3. Trial Design

The registry describes a Phase I/IIa study of retapamulin ointment, 1%, applied twice daily to the anterior nares of healthy adults carrying Staphylococcus aureus. It lists the trial as Phase 2, randomized, double-blind, and placebo-controlled. The status is completed, and the recorded enrollment is 57. The listed study start is 2007-09, and primary completion is recorded as 2008-01.

Three treatment regimens appear in the arm descriptions. Treatment A used retapamulin twice daily for 3 days and placebo twice daily for 2 days, for a total of 5 days. Treatment B used retapamulin twice daily for 5 days. Treatment C used placebo twice daily for 5 days. The descriptions record each dose as 200mg BID. The record does not explain further details of the treatment allocation or the rationale for these regimens.

The brief description says participants would be stratified as persistent or intermittent carriers, with a planned 2:1 ratio and target completion counts of at least 38 persistent carriers and 19 intermittent carriers. These are design statements, not a report of the final number in either carrier category. The record describes up to three screening visits, a treatment period, and two follow-up visits, with participation expected to last approximately 6 to 10 weeks from screening through the last follow-up.

The registry classifies the model as single group, while also describing randomization and listing three treatment regimens. That classification and the arm descriptions do not form a fully consistent account of the design structure. The available record does not resolve the discrepancy, so the treatment descriptions can be reported, but the model classification should be read cautiously.

GlaxoSmithKline is listed as the sponsor. The record does not report the allocation sequence method, concealment procedures, detailed blinding procedures, or a sample-size justification. Those design details should not be inferred from the randomized and double-blind labels alone.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) Concentration Population - included all subjects who underwent plasma PK sampling

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 Plasma Retapumulin Pharmacokinetic Parameters by Treatment at Days 1 and 3 Evaluated by Plasma AUC After Dosing, measured over Days 1 and 3.

The primary outcome is titled as plasma retapamulin pharmacokinetic parameters by treatment at Days 1 and 3, evaluated by plasma AUC after dosing. AUC, or area under the plasma concentration-time curve, summarizes drug concentration in plasma over time. The registry describes it as a measure used to calculate drug clearance and bioavailability using the concentration-time curve.

In general, pharmacokinetic measurements help characterize how much drug is present in the body over a specified sampling period. AUC is useful because it incorporates concentration measurements across time rather than relying on a single plasma concentration. It can therefore describe overall systemic exposure during the period measured. It is not itself a measure of nasal bacterial eradication or a clinical benefit.

The endpoint specifies a mean and standard deviation, with units of ng.h /mL and a timeframe of Days 1 and 3. The population is defined as participants who underwent plasma pharmacokinetic sampling. The record does not report the treatment-specific AUC means or standard deviations, the sampling schedule, or a contrast between treatment groups. Consequently, the endpoint definition is available, but the magnitude and variability of the observed plasma exposure are not reported in the registry record.

The secondary outcomes include additional pharmacokinetic parameters at Day 5 as well as measures of nasal carriage, recolonization, and pharyngeal carriage. Those outcomes address questions distinct from the primary AUC measure and should be interpreted separately.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods can be understood by separating the design, outcome measurement, and statistical summaries. The registry describes randomization, double blinding, placebo control, three treatment regimens, and a primary pharmacokinetic outcome. It does not report enough detail to reconstruct the full analysis plan or the comparisons actually carried out.

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance. If implemented successfully, it can reduce systematic differences between groups at the start of a trial. The registry identifies the study as randomized, but does not report the sequence-generation or allocation-concealment methods. It is therefore possible to describe the design as randomized, but not to assess those specific procedures from the record.

Blinding is intended to reduce the influence of treatment knowledge on participant behavior, clinical assessment, and outcome recording. The registry labels the study double-blind and placebo-controlled. It does not specify who was blinded or how the blinding was maintained. Placebo was listed as a treatment regimen, and another regimen used retapamulin for part of the treatment period and placebo for the remainder.

What does the primary measure summarize?

Plasma AUC summarizes concentration over time. In general, a concentration-time curve is built from plasma samples collected at specified times, and its area represents overall measured exposure across the sampling interval. The registry says AUC is used to calculate drug clearance and bioavailability. The reported endpoint uses the mean and standard deviation and names ng.h /mL as its unit. However, the actual means and standard deviations are not reported in the registry record, and the sampling schedule is not described.

A mean is a measure of the center of a set of observations. A standard deviation describes how spread out observations are around their mean. They answer different questions: the mean characterizes typical measured exposure, while the standard deviation characterizes variability among measured observations. Neither can be interpreted for the trial groups without the numerical results. The endpoint population includes all subjects who underwent plasma PK sampling; the record does not give the number sampled or state how missing samples were handled.

Why do comparisons need an estimate and uncertainty?

In general, a treatment comparison is most informative when it reports an estimated difference or other contrast together with an uncertainty measure, such as a confidence interval. The estimate describes the observed size and direction of the contrast. The interval shows how imprecise that estimate may be under the assumptions of the analysis. A p-value addresses compatibility with a specified null hypothesis, but does not by itself describe the size or clinical meaning of an effect.

No primary-outcome contrast, confidence interval, or p-value is reported in the registry record. The number of analyses listed in the record does not identify which contrasts were prespecified or how they were analyzed. It also does not establish whether the reported endpoint was adjusted for baseline values or other factors. Those analysis details are not reported in the registry record.

How should repeated outcomes be considered?

The registry lists outcomes at multiple visits, including Days 1 and 3 for pharmacokinetic measures, Day 5 for another pharmacokinetic outcome, and several follow-up times for carriage outcomes. In general, repeated measurements can be analyzed as separate visit-specific outcomes or with a model that accounts for within-participant correlation. Those approaches can produce different estimates and uncertainty. The record does not report which approach was used for repeated measurements or how the visit-specific comparisons were selected.

Some carriage outcomes are expressed as percentages of participants with a specified status, while the primary outcome is a continuous pharmacokinetic measure summarized as a mean and standard deviation. These outcome types require different summaries and may require different statistical models. The registry does not provide the numerical carriage results or the analysis methods used for them.

What role do planning calculations play?

In general, sample-size planning calculations estimate how many participants may be needed to detect an assumed effect under stated statistical assumptions. A planning illustration based on an observed effect is not an observed trial result and is not observed power. The sample-size assumptions described for this record refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of an observed effect. The assumptions describe an illustration, not necessarily the original design rationale. The registry does not report the trial's own sample-size justification or identify a prespecified target effect for the primary outcome.

Planning calculations depend on assumptions about effect size, variability, allocation, and analysis. If those assumptions do not match the actual trial design or outcome distribution, the resulting participant counts may not represent the requirements for this study. The record does not provide numerical planning outputs or establish that those calculations were part of the original protocol.

For count outcomes, the observed number of participants with an event is distinct from a modeled treatment effect. The adverse-event figures in the registry are counts with denominators, not adjusted comparisons. In general, sparse events can make comparative estimates imprecise. The registry does not report comparative safety estimates or uncertainty intervals, so the counts should be read descriptively.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary pharmacokinetic outcome and multiple secondary outcomes, including measures at several visits and outcomes stratified by carrier or pharyngeal status. When an analysis tests many outcomes or contrasts, the chance of at least one apparently unusual result can increase. General approaches to multiplicity include prespecifying a hierarchy, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report whether any multiplicity approach was used, which outcomes were included in any testing hierarchy, or whether analyses were prespecified.

Missing-data methods are also not reported in the registry record. The primary pharmacokinetic population is defined as participants who underwent plasma sampling, but the record does not state how many participants contributed samples at each time point, whether any samples were unusable, or how missing measurements were handled. It does not report missingness for the carriage or safety outcomes.

The brief description gives planned carrier stratification and target numbers for persistent and intermittent carriers. It does not report the final numbers in those categories or show whether all enrolled participants completed follow-up. The recorded enrollment of 57 should not be taken as evidence that every participant contributed to every analysis.

The primary outcome population and the overall enrolled population are not necessarily identical: the former is defined by plasma sampling. The record does not provide enough detail to determine whether analyses followed randomized assignment, used only participants with available outcome measurements, or used another analysis population for each endpoint. Definitions of analysis populations beyond the stated pharmacokinetic population are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (5.3%).

The registry records serious adverse events separately from other adverse events. For retapamulin for 3 days, 0 of 23 participants at risk had a serious adverse event, and 6 of 23 had another adverse event. For retapamulin for 5 days, 1 of 19 had a serious adverse event, and 10 of 19 had another adverse event. For placebo, 0 of 15 had a serious adverse event, and 5 of 15 had another adverse event.

These figures count participants, not the total number of distinct events. They are descriptive records for the groups and do not show whether an event was judged related to treatment. The registry does not report comparative risk estimates or confidence intervals, so the counts alone do not quantify the precision of differences between regimens.

Abdominal Pain is listed among the top serious terms at 5.3%. The record does not give further context for this percentage. Death counts are not reported in the registry record. The reported counts should therefore be read as a limited safety summary, not as a complete account of event timing, severity, attribution, or comparative risk.

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

The record describes a randomized, double-blind, placebo-controlled study of retapamulin ointment in healthy adults carrying Staphylococcus aureus. Its primary outcome concerns plasma drug exposure after dosing, and its secondary outcomes include additional pharmacokinetic measures and nasal or pharyngeal carriage outcomes. This makes the registry record useful for understanding the study's stated questions and treatment regimens.

The primary outcome results are not reported in the registry record. As a result, the record does not establish the observed AUC in any group, the variability in those measurements, or how plasma exposure differed across the regimens. It also does not report numerical results for the listed carriage outcomes. The outcome descriptions should not be mistaken for evidence of an observed result.

The adverse-event counts provide some descriptive information: serious adverse events were recorded for 0 of 23 participants in the 3-day retapamulin group, 1 of 19 in the 5-day retapamulin group, and 0 of 15 in the placebo group. Other adverse events were recorded for 6 of 23, 10 of 19, and 5 of 15 participants. These counts do not supply an adjusted comparison or a measure of statistical precision.

In general, a registry record may describe a planned study and selected reported outcomes without presenting a full statistical report. Here, the record does not report the analysis methods needed to evaluate the precision of the pharmacokinetic or carriage findings, nor does it report confidence intervals or p-values for the primary outcome. It therefore cannot establish the size or certainty of any treatment contrast on those outcomes.

The study population was healthy adult nasal carriers, not a population described as having a clinical infection requiring treatment. The study's carriage outcomes and pharmacokinetic outcomes have their own definitions and should not be equated with clinical outcomes beyond those measures. The record supports a limited account of design and event counts; it does not by itself support broader conclusions about clinical effects.

13. Why This Trial Matters Statistically

This trial illustrates why the outcome named as primary matters when interpreting a study. The primary measure is plasma AUC, a pharmacokinetic measure of systemic exposure. The registry also lists bacterial carriage outcomes, but these are separate questions. A reader should not treat a listed secondary outcome as though it were the primary endpoint, or infer an outcome result from its description alone.

The record also highlights the difference between design information and results. Randomization, masking, placebo control, treatment schedules, and the planned carrier stratification help describe how the study was organized. They do not reveal the observed AUC or carriage outcomes. Without the numerical outcome summaries and uncertainty estimates, the magnitude and precision of the findings cannot be evaluated.

Safety counts demonstrate another statistical distinction: a count with a denominator is useful descriptive information, but it is not equivalent to a comparative estimate. In general, uncertainty is important when interpreting event counts, particularly when counts are small. The record does not provide confidence intervals or formal between-group safety comparisons.

Finally, registry records can leave important analysis details unresolved. Here, the listed model classification does not align clearly with the description of randomization and three treatment regimens. The record also does not report multiplicity procedures, missing-data methods, or a sample-size justification. Recognizing these gaps is part of sound statistical interpretation: conclusions should remain tied to the information actually recorded and should not extend beyond the reported outcomes.

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 largest limitation for interpreting efficacy and pharmacokinetics is the absence of numerical outcome results. The primary AUC means and standard deviations are not reported in the registry record, nor are treatment contrasts or uncertainty estimates. Numerical results for the listed nasal and pharyngeal carriage outcomes are also not reported. This prevents assessment of their magnitude and precision.

The design description has an unresolved classification inconsistency. The registry labels the model as single group while describing a randomized, double-blind, placebo-controlled study with three treatment regimens. The record does not explain that discrepancy. It also does not report how randomization was generated or concealed, who was blinded, or how masking was maintained.

Important analysis details are missing. The record does not describe the statistical methods used for the primary or secondary outcomes, any multiplicity adjustment, missing-data handling, or analysis populations beyond the stated pharmacokinetic population. It does not report the number of participants contributing outcome data at each visit. Planned carrier targets are described, but final carrier-category counts are not reported.

The safety summary is limited to participant counts with serious and other adverse events. It does not provide comparative estimates or uncertainty intervals, and the context for the listed Abdominal Pain percentage is not explained. Death counts are not reported in the registry record. These limitations mean that event counts cannot provide a complete account of safety or its precision.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Retapamulin Ointment in Healthy Adults Nasally Colonized With Staphylococcus Aureus — NCT00539994.
• Registry record last updated 2016-12-15; status last verified 2016-11.
• Results first posted 2010-08-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed Phase 2 randomized, double-blind, placebo-controlled study sponsored by GlaxoSmithKline, with enrollment of 57. It evaluated retapamulin ointment, 1%, applied twice daily to the anterior nares of healthy adults carrying Staphylococcus aureus. The listed regimens were retapamulin for 3 days followed by placebo for 2 days, retapamulin for 5 days, and placebo for 5 days.

The primary outcome was plasma pharmacokinetic parameters, including AUC after dosing on Days 1 and 3, among participants who underwent plasma sampling. Secondary outcomes included additional pharmacokinetic measures and nasal and pharyngeal carriage outcomes. Numerical results for these outcomes are not reported in the registry record. Adverse-event counts are reported by group, but comparative estimates and uncertainty measures are not.

The record does not report the full statistical analysis plan, missing-data procedures, multiplicity methods, or sample-size justification. Its model classification is not fully consistent with its description of multiple randomized treatment regimens.