Safety, Tolerability and Pharmacokinetics (PK) Study of GSK2269557 in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Pharmacokinetics (PK) Study of GSK2269557 in Healthy Subjects (NCT03189589), a randomized phase 1 study. The primary outcome is Mean GSK2269557 Plasma Concentration.

2. Clinical Question

The clinical question is pharmacokinetic rather than an assessment of clinical benefit. The record describes this as the first study of a new formulation in healthy subjects and says the data were intended to inform the pharmacokinetic profile and systemic exposure expected during Phase 2b. That intention does not establish what the later study found, or whether a particular exposure was achieved.

The two dose groups allow concentration measurements after different single-dose amounts to be considered in the same study framework. Because there was no placebo arm in the listed interventions, the design is not a placebo-controlled efficacy comparison. It instead describes the measurement of plasma drug concentrations and the monitoring of safety and tolerability after inhalation.

The primary question is not answered numerically by the posted results described in the registry record: means and standard deviations for the scheduled measurement times are not reported in the registry record. Consequently, the record does not allow a reader to judge the size or precision of any difference in concentration between the dose groups.

3. Trial Design

This was a randomized, double-blind, parallel-group Phase 1 study sponsored by GlaxoSmithKline. The registry record gives enrollment as 12 and status as completed. The study started on 2017-06-15, and primary completion was recorded as 2017-07-24. The record describes three study phases: screening, treatment, and follow-up. The total duration for each participant was planned to be up to 6 weeks.

Participants were assigned to receive a single inhaled dose of GSK2269557 500 µg or GSK2269557 750 µg using the ELLIPTA dry powder inhaler. The randomized, parallel-group structure means the listed groups received different assigned doses rather than crossing over between doses. The record identifies double masking, but does not report the practical masking procedures or which study roles were masked.

The planned enrollment was described as approximately twelve healthy subjects, while the registered enrollment is 12. The adverse-event record lists 6 participants at risk in each dose group. The registry describes the pharmacokinetic population as participants randomized in the safety population for whom a pharmacokinetic sample was obtained and analyzed. It does not report the number included in that population.

Whole blood samples of approximately 2 milliliters were collected at the scheduled time points to measure plasma concentrations. The schedule began before dosing on Day 1 and continued after dosing through Day 6. The listed times were 5 minutes, 30 minutes, 2 hours, 6 hours, and 12 hours after dosing on Day 1; 24 hours on Day 2; 48 hours on Day 3; and 120 hours on Day 6.

The registry also lists safety and tolerability outcomes, including vital signs, electrocardiogram values, lung-function changes, hematology and clinical chemistry abnormalities, adverse events, and serious adverse events. These outcomes broaden the description beyond pharmacokinetics, but detailed results for most are not reported in the registry record. The study design and monitoring do not, by themselves, establish safety or clinical benefit.

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 19 participants were screened for this study, of which 7 participants were screen failures and 12 participants were randomized to treatment. The reasons for screen failure were: did not meet inclusion/exclusion criteria (6 participants) and withdrawal by participant (1 participant).

Overall Study

Analysis population for the primary outcome, as defined in the registry: PK 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 Mean GSK2269557 Plasma Concentration, measured over Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose.

The primary endpoint was mean plasma concentration of GSK2269557, expressed in picograms per milliliter. A plasma concentration is a measurement of the amount of a substance present in the sampled blood compartment at a specified time. The endpoint was assessed at multiple scheduled times after the single inhaled dose, with a pre-dose measurement also specified.

Repeated measurements are used in pharmacokinetic studies to describe how concentration changes over time after administration. Considering measurements at several post-dose times can characterize the observed concentration profile more fully than a single measurement. The registry says pharmacokinetic parameters were calculated by standard non-compartmental analysis. General explanation: non-compartmental approaches use observed concentration and time data to estimate pharmacokinetic features without requiring the investigator to specify a compartment model. The registry record does not report the particular parameter estimates.

The endpoint is relevant to the study’s stated purpose of describing pharmacokinetics and systemic exposure for this formulation. It is not an endpoint of symptom improvement, disease control, or comparative clinical efficacy. The participants were described as healthy, and the record does not report a clinical outcome comparison in people with chronic obstructive pulmonary disease.

The registry names the summary measure as a mean and its dispersion as a standard deviation. General explanation: the mean describes the central value across observations, while the standard deviation describes how spread out those observations are around the mean. Neither measure is reported numerically for the scheduled concentration outcomes in the registry record. As a result, the endpoint definition and measurement schedule are available, but the observed concentration profile and its variability are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure represent?

The primary measure is mean plasma concentration, with units of picograms per milliliter. It is a continuous outcome: a measured quantity that can take a range of values. The measurement schedule includes a pre-dose sample and repeated post-dose samples. The registry says whole blood samples of approximately 2 milliliters were collected for plasma concentration measurement. This schedule defines when concentration observations were intended to be taken; it does not give the values observed at those times.

The registry names standard deviation as the dispersion measure. General explanation: the mean describes the average concentration in a set of observations, while the standard deviation describes their spread around that average. A mean alone can obscure whether observations are tightly grouped or widely spread. Reporting both can therefore help characterize a continuous outcome. The registry record does not report either measure numerically for the primary outcome.

What is non-compartmental analysis?

The record says pharmacokinetic parameters were calculated by standard non-compartmental analysis. General explanation: this family of methods uses measured concentrations over time to derive pharmacokinetic summaries without defining the body as a set of modeled compartments. Such calculations depend on the observed concentration-time data and on the specified analysis choices. The record does not list the parameter estimates, detailed calculation choices, or concentration data, so no parameter can be reconstructed from the measurement schedule alone.

What does the randomized parallel design contribute?

Random allocation is intended to reduce systematic differences in assignment to the dose groups. A parallel-group design assigns participants to a group and observes them under that assignment, rather than having each participant receive both doses. General explanation: randomization supports a fair comparison by making assignment less dependent on participant characteristics, but it does not guarantee that groups will be identical, especially in a small study. The registry describes the design as randomized and parallel, but does not report the randomization sequence, allocation concealment procedures, or baseline group characteristics.

Double masking is also stated. General explanation: masking can reduce the influence of knowledge about assigned treatment on participant experience, study conduct, or outcome assessment, depending on who is masked and how. The registry record does not specify the masked roles or procedures. Therefore, the designation describes the registered design but does not permit a detailed assessment of how masking was maintained.

How should repeated measurements be understood?

Concentrations were scheduled at several points after dosing. Repeated observations can describe change over time, but observations from the same participant are related rather than independent. General explanation: an analysis of repeated measurements should account for that relationship if it uses multiple observations together. A separate comparison at each time point, a model of the full profile, and a derived pharmacokinetic summary are different approaches and answer different questions. The registry record does not report which inferential approach, if any, was used for the primary concentration outcome.

The primary outcome has several categories or time points and is not reduced to one comparison in the registry record. No analysis results are listed. Thus there is no basis to select a particular time-point comparison, combine times into a new summary, or describe a concentration difference as statistically significant or not statistically significant.

What do uncertainty measures add?

General explanation: a confidence interval is a range of values compatible with the data under a stated statistical procedure. It communicates uncertainty around an estimate and is not a guarantee that the true value lies within the specific interval. A standard deviation and a confidence interval serve different purposes: standard deviation describes spread among observations, while a confidence interval describes uncertainty in an estimated quantity. No confidence intervals for the primary endpoint are reported in the registry record.

General explanation: small samples often leave estimates imprecise, but the amount of uncertainty cannot be quantified without the actual observations or reported uncertainty measures. The registered enrollment is 12, and the adverse-event groups each list 6 participants at risk. These counts describe the study size; they do not provide an estimate of precision for unreported concentration outcomes.

What do the planning assumptions mean?

The stated sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration is not the trial’s own design justification. The stated effect to detect is a fraction of the observed effect. General explanation: a sample-size calculation depends on assumptions about the effect size, variability, error rate, and analysis. Changing those assumptions changes the resulting planning estimate.

Any such illustration is a planning tool, not observed power and not evidence that a study had a particular probability of detecting an effect. The record does not report the protocol’s sample-size justification. It also does not report a primary effect estimate from which a reader could independently assess the illustrated planning assumptions. No planning count or observed-power claim can be inferred from the registered enrollment alone.

10. Multiplicity, Missing Data and Analysis Populations

The primary concentration outcome is scheduled at several time points. Looking at multiple outcomes or time points can raise a multiplicity question: repeated statistical testing may increase the chance of finding an apparently notable result by chance if no adjustment or prespecified strategy is used. General explanation: an analysis plan can address this by specifying a primary time point, a combined endpoint, a testing sequence, or an adjustment method. The registry record does not report a multiplicity strategy, and it does not reduce the primary outcome to one comparison.

The registry lists 10 outcome measures and 0 analyses. It gives several secondary safety and lung-function outcomes, including vital signs, ECG values, FVC and FEV1 changes, laboratory abnormalities, and adverse events. Results for these outcomes are not reported in the registry record apart from the adverse-event counts described separately. Without analysis details and results, it is not possible to assess which outcomes were emphasized or how multiple comparisons were handled.

Missing-data methods are not reported in the registry record. The record does not state whether any scheduled samples or outcome assessments were missing, how missing measurements were handled, or whether sensitivity analyses were conducted. This is important for repeated concentration measurements because an incomplete profile may affect summaries that use observations across time. The record’s definition of the pharmacokinetic population requires a sample to have been obtained and analyzed, but it does not give the number meeting that definition.

The record defines the pharmacokinetic population as randomized participants in the safety population for whom a pharmacokinetic sample was obtained and analyzed. It refers to a safety population but does not provide further population definitions or the analysis population used for each outcome. Thus, the population rule is stated for pharmacokinetics, but the analysis populations and handling of missing outcome data are not fully described in the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 0 participants with serious adverse events among 6 at risk in the GSK2269557 500 mcg group, and 0 among 6 at risk in the GSK2269557 750 mcg group. It also lists 3 participants with other adverse events among 6 at risk in each group. The record’s top serious adverse-event terms list is empty.

These are counts of participants, not a complete description of each event’s nature, timing, severity, or relationship to study treatment. The record does not provide the terms for the other adverse events or further detail about the serious-event assessment. It also does not report the results for the other listed safety outcomes, such as vital signs, ECG values, lung function, hematology, or clinical chemistry.

General explanation: observing no serious adverse events in a small study is not proof that the risk is absent. The amount of information about uncommon events is limited when few participants are observed. Likewise, matching counts between groups do not establish that the groups have the same safety profile. The figures are descriptive and should be read as the recorded counts for this study, not as a definitive comparison or a broad safety conclusion.

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

The registry record documents a randomized, double-blind, parallel-group Phase 1 study of single inhaled doses of GSK2269557 500 µg and 750 µg in healthy participants. Its primary endpoint was mean plasma concentration across a scheduled series of measurements, with standard deviation named as the dispersion measure. This describes the intended pharmacokinetic assessment and the way the endpoint was characterized.

The record does not report the actual plasma concentration means, standard deviations, pharmacokinetic parameter estimates, or inferential results. It therefore does not show how concentrations changed over time, how the groups differed, or how precise any estimated difference might be. Dose amounts alone cannot substitute for observed concentration data. The stated purpose of informing expectations for Phase 2b is an aim of the study, not evidence that any particular exposure was achieved.

The adverse-event record reports no participants with serious adverse events in either group and 3 participants with other adverse events in each group, with 6 at risk in each. These counts are useful as a limited descriptive record, but they do not demonstrate identical safety, exclude unobserved events, or establish a treatment effect.

The findings should not be interpreted as evidence of clinical efficacy. The study enrolled healthy participants, used single doses, and focused on pharmacokinetics, safety, and tolerability. The registry record does not report a clinical efficacy outcome or a placebo comparison. It also does not report results for most listed secondary outcomes, analysis details, or missing-data methods.

General explanation: a study’s design tells readers what question it was arranged to address, while its results determine what can be concluded from the observed data. When numerical results are absent, careful interpretation is limited to the design, planned measurements, and any posted counts. Here, the registry supports those descriptions but not a numerical conclusion about concentration differences or a broader conclusion about clinical benefit.

13. Why This Trial Matters Statistically

Pharmacokinetic studies provide a structured way to describe how a drug appears in plasma over time after administration. This study’s schedule, from pre-dose through 120 hours after dosing, was designed to capture measurements at several stages after a single inhaled dose. The record also specifies a new formulation and an inhaler, making the formulation and delivery method part of the study context rather than incidental details.

The randomized parallel-group design offers a framework for comparing two dose groups, while the double-blind designation signals an effort to mask assignment. The enrollment was 12, and the record lists 6 participants at risk in each dose group for adverse events. Those details help readers understand the scale and structure of the investigation, while also underscoring that its safety counts are descriptive and limited in scope.

Statistically, the study illustrates why an endpoint definition is not a result. The registry specifies mean plasma concentration and standard deviation, but does not report their values. Without the measurements or estimates, readers cannot quantify the concentration profile, its variability, or the precision of a comparison. The measurement schedule and analysis description identify the intended approach but cannot replace the absent outcome results.

The study also illustrates the distinction between a planning exercise and a trial’s own design rationale. The stated assumptions describe a sample-size planning illustration, not the protocol’s justification and not observed power. General explanation: planning calculations depend on assumptions and should not be interpreted as evidence about what the trial actually detected. The registry record does not report its sample-size justification.

Finally, the study’s stated aim was to inform expectations for Phase 2b. That makes its pharmacokinetic objective clear, but the aim is not itself a finding. A clear statistical reading preserves the distinction between the intended use of the data, the measurements planned, and the results actually reported.

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 primary limitation for interpreting this record is that the numerical results for mean plasma concentration and standard deviation are not reported in the registry record. The record gives the endpoint definition and measurement schedule but not the observed concentration values or derived pharmacokinetic estimates. This prevents assessment of the concentration profile and of any difference between dose groups.

The record describes several scheduled time points but does not state a single primary comparison, an inferential method, confidence intervals, or a multiplicity strategy. It lists 0 analyses. No missing-data approach, number of analyzed pharmacokinetic participants, or sensitivity analysis is reported in the registry record. These omissions limit assessment of how repeated measurements and incomplete observations were handled.

The study enrolled 12 healthy participants and involved single doses. Its scale and population constrain how broadly its descriptive safety information can be interpreted. The registry lists 6 participants at risk in each group, with no serious adverse events recorded and 3 participants with other adverse events in each. Detailed event terms and results for most listed safety and secondary outcomes are not reported in the registry record.

The record identifies the study as double-blind and randomized but does not describe the masking procedures, allocation concealment, or baseline characteristics by group. It also does not report the protocol’s sample-size justification. These details would be relevant to a fuller assessment of design and analysis, but should not be inferred from the registered labels alone.

The registry lists Pulmonary Disease, Chronic Obstructive as a condition while describing the participants as healthy. The results therefore should not be treated as direct evidence about clinical outcomes in people with that disease. The stated intention to inform later-phase exposure expectations is not a substitute for reported results or for evidence from a different study population.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability and Pharmacokinetics (PK) Study of GSK2269557 in Healthy Subjects — NCT03189589.
• Registry record last updated 2019-08-19; status last verified 2019-08.
• Results first posted 2019-01-14.
• 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.

18. Record Summary

NCT03189589 is a completed Phase 1 randomized, double-blind, parallel-group study sponsored by GlaxoSmithKline. It enrolled 12 healthy participants and compared single inhaled doses of GSK2269557 500 µg and 750 µg using the ELLIPTA dry powder inhaler. The registry records a start date of 2017-06-15 and primary completion on 2017-07-24.

The primary outcome was mean plasma concentration, measured from pre-dose through 120 hours after dosing; standard deviation was specified as the dispersion measure. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. The actual concentration results and pharmacokinetic estimates are not reported in the registry record.

The adverse-event record lists 0 serious adverse events and 3 participants with other adverse events in each dose group, with 6 at risk per group. The registry lists 10 outcome measures and 0 analyses. Detailed results for most secondary outcomes, multiplicity methods, missing-data methods, and the protocol’s sample-size justification are not reported in the registry record.