A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010 (NCT03311373), a randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax)-Budesonide.

2. Clinical Question

3. Trial Design

The registry record describes NCT03311373 as a randomized, open-label, single-dose, single-center crossover study of PT010 in healthy subjects. It is listed as Phase 1, with an enrollment of 56. The study status is completed. The recorded start date is 2017-10-17, and the primary completion date is 2017-12-15. The record lists Chronic Obstructive Pulmonary Disease as the condition, although both the title and summary describe healthy subjects. The record does not explain this difference.

A crossover design means that participants receive more than one treatment condition in successive periods, so comparisons can use observations from the same participant under different regimens. This can reduce the influence of stable participant-to-participant differences, although interpretation also depends on treatment sequence, period effects, and any carryover between periods. These are general features of crossover studies, not findings about this trial. The record identifies four treatment periods and four regimen labels. Its period descriptions indicate test formulation as Regimen B or D and reference formulation as Regimen A or C, but the exact sequence assignments and the regimen-to-condition mapping are not reported in the registry record.

The official title says the study assesses relative bioavailability when PT010 is administered with and without a spacer, and with and without oral charcoal. The listed interventions are Regimens A, B, C, and D. Regimen-specific administration details, dose information, washout duration, and the randomization sequence are not reported in the registry record. The study is unmasked, so it is open-label. The record does not describe any blinding of laboratory or statistical assessment.

The primary measure is budesonide Cmax, the maximum observed plasma concentration following dosing. The stated collection timeframe runs from pre-dose through 24 h post-dose, with measurements at the listed intermediate times. Secondary outcomes include Tmax and AUC0-∞ for budesonide, glycopyrronium, and formoterol. The record lists 12 outcome measures and six posted secondary outcomes. Detailed results for those secondary outcomes are not included in the registry entries. The record does not report a rationale for the enrollment target, a formal sample-size justification, or whether any interim analyses were planned or performed.

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: Elig subj. received single dose of BGF MDI (Budesonide, Glycopyrronium, and Formoterol Fumarate metered dose inhaler) 320/28.8/9.6 μg as: Regimen A: BGF MDI w/out spacer, w/out charcoal Regimen B: BGF MDI with spacer, w/out charcoal Regimen C: BGF MDI w/out spacer, with charcoal Regimen D: BGF MDI with spacer, with charcoal

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.

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 Maximum Plasma Concentration (Cmax)-Budesonide, measured over Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose.

The primary endpoint is maximum plasma concentration (Cmax) of budesonide, measured in pg/mL and summarized by geometric mean for each regimen. Cmax is the highest plasma concentration observed after administration during the stated sampling period. The record lists samples from pre-dose and 2, 6, 20, and 40 min, and 1, 2, 4, 8, 12, and 24 h post-dose. Cmax describes the observed peak exposure; it does not by itself describe the full concentration-time profile or total drug exposure.

Pharmacokinetic studies commonly use Cmax to characterize peak systemic exposure and to compare formulations or administration conditions. That is general background. The title frames this study as an assessment of relative bioavailability, but the posted primary result is a set of regimen-specific geometric means rather than a reported relative-bioavailability estimate. The record does not provide a confidence interval, formal contrast, or prespecified equivalence range for the primary endpoint. Consequently, the listed summaries can describe observed peak concentrations but cannot, on their own, establish the precision of a comparison or whether a formal bioequivalence criterion was met.

The registry states that the primary endpoint uses the pharmacokinetic population: subjects in the Safety Population for whom at least one primary pharmacokinetic parameter for an analyte could be calculated and who had no important protocol deviations thought to affect pharmacokinetic analysis. The record does not give a more detailed endpoint derivation algorithm or explain handling of samples below quantification limits.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary endpoint is a pharmacokinetic measurement, not a clinical event count. It records the maximum plasma concentration of budesonide during the specified sampling period. The registry reports the endpoint as a geometric mean and gives a geometric coefficient of variation for each regimen. The values are therefore summaries of concentration data on a multiplicative scale. The record does not supply individual concentration measurements, so the calculations cannot be independently reproduced from the posted summaries.

Why use a geometric mean?

Pharmacokinetic concentrations are often positively skewed: many observations may lie toward the lower end while a smaller number are much higher. A geometric mean is calculated on a logarithmic scale and then expressed back on the original scale. In general, this can make a central summary more appropriate when variation is multiplicative rather than additive. This is general statistical context; the registry record does not state why this summary was selected for this endpoint or describe the distributional checks performed.

A geometric coefficient of variation expresses relative spread rather than spread in the original concentration units. It is useful when comparing variability across measurements with different magnitudes. A larger reported coefficient indicates more relative variability. It should not be mistaken for a confidence interval: it describes dispersion in the data, whereas a confidence interval quantifies uncertainty about an estimated quantity under a specified statistical procedure. No confidence interval for the primary endpoint is reported in the registry record.

What does the crossover design change?

In a crossover study, participants receive multiple treatment conditions in separate periods. A statistical analysis can compare measurements within participants, which may account for stable characteristics shared by that participant's observations. The analysis may also need to address period, sequence, and carryover effects. These are general methodological considerations. The record identifies a randomized crossover design and four treatment periods, but it does not report the treatment sequences, washout duration, crossover model, or estimates for period or sequence effects.

The descriptive endpoint entries give a mean and variability for each regimen. They do not show the within-participant covariance or paired differences. Those elements matter because a crossover comparison's precision depends not only on the separate regimen summaries but also on how measurements from the same participants relate to one another. It would be inappropriate to reconstruct a paired treatment estimate from the marginal means alone. The registry does not provide the data or model output needed for that reconstruction.

What can be inferred from the posted summaries?

The regimen-specific geometric means describe the observed concentration scale for budesonide Cmax. The geometric coefficients of variation describe relative dispersion within the corresponding regimen summaries. They do not show how precisely a difference between regimens is estimated. A formal comparison would ordinarily report an effect estimate on an appropriate scale, an uncertainty interval, and potentially a test result. The record posts none of these for the primary endpoint. It also does not identify a single primary contrast across the four regimens. The values should consequently be read descriptively rather than as proof that one regimen differs statistically from another.

The number of participants listed for each regimen outcome is 52. In a crossover design, the same person may contribute observations under more than one regimen. These regimen-specific counts should not be added to estimate the number of unique participants. The enrollment entry is 56, while the endpoint population definition refers to subjects with calculable pharmacokinetic parameters and without important protocol deviations affecting analysis. The registry does not provide a participant-flow account linking enrollment to the endpoint summaries.

What is reported about planning and inference?

The record contains a general planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is described as varying the effect to detect as a stated fraction of the observed effect; the specific resulting planning values are not included in the registry entries. Such calculations are hypothetical design illustrations, not observed power and not evidence that the original trial was designed around those assumptions. The trial's own sample-size justification and statistical plan are not reported in the registry record.

The registry record lists zero analyses for this outcome. That means no inferential analysis result is posted in the record; it does not establish what analyses may have been conducted outside the registry submission. No information is reported on model specification, covariate adjustment, confidence-interval method, missing-data methods, multiplicity control, or the handling of protocol deviations beyond the stated pharmacokinetic population definition. Those omissions limit the strength of any statistical conclusion that can be drawn from the endpoint summaries.

General statistical interpretation distinguishes description from inference. A descriptive result reports what the observed data summaries look like. Inference uses a defined model or sampling framework to quantify uncertainty and assess how compatible the observations are with specified hypotheses. Here, the regimen means support a description of observed budesonide Cmax, while the absence of reported contrast estimates and uncertainty measures prevents a formal assessment of the comparative evidence. The posted values should not be extended to unreported analytes, secondary endpoints, clinical outcomes, or administration details that are not mapped to the regimen labels.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures and six posted secondary outcomes. The secondary outcomes include Tmax and AUC0-∞ for budesonide, glycopyrronium, and formoterol. The primary result discussed is budesonide Cmax. The record lists zero analyses for the outcome. Detailed results for the secondary outcomes are not reported in the registry entries.

When a study examines multiple endpoints, treatment contrasts, or time points, the chance of obtaining at least one apparently unusual result can increase. Statistical plans may address this through a prespecified hierarchy, adjustment, or a clearly defined distinction between primary and exploratory analyses. This is general statistical context. The registry record does not report a multiplicity strategy, endpoint hierarchy beyond identifying the primary outcome, or a plan for interpreting multiple regimen comparisons. It is therefore not possible to determine whether or how multiplicity was considered.

The record's primary pharmacokinetic population includes subjects in the Safety Population for whom at least one primary pharmacokinetic parameter for an analyte could be calculated and who had no important protocol deviations thought to affect pharmacokinetic analysis. This defines an analysis population in broad terms, but the record does not state the participant-level reasons for missing or uncalculable parameters, the number excluded, or whether any missing values were imputed. Missing-data handling is not reported in the registry record.

The enrollment entry is 56, while each regimen's primary outcome entry lists 52 participants. Because crossover participants may contribute to multiple regimen summaries, those entries do not represent separate groups of unique participants and should not be summed. The record does not explain the difference between enrollment and endpoint counts. It also does not report whether any participants discontinued, which treatment periods or samples were incomplete, or how protocol deviations were assessed.

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 2% reporting threshold.

Most frequent non-serious adverse event terms

The posted safety entries report no serious adverse events for any listed regimen group and no deaths. The numbers listed as at risk for serious events are 53 for Regimen B and 52 for each of Regimens A, C, and D. For other adverse events, the record lists 4 affected for Regimen B, 1 for Regimen A, 4 for Regimen C, and 4 for Regimen D; the corresponding at-risk entries are 53 for Regimen B and 52 for each of the other regimens.

These are regimen-specific registry counts. In a crossover study, participants may appear in more than one regimen's safety accounting, so the groups should not be treated as independent sets of people or added to derive an overall participant count. The record does not clarify whether the affected counts refer to people or event occurrences beyond the registry's affected-count field, and it does not provide event descriptions or severity details in the registry entries. No serious adverse-event terms are listed.

Zero recorded serious events in these entries describes the registry report; it does not demonstrate the absence of risk. Safety interpretation depends on the events collected, exposure, follow-up, and completeness of reporting. The record does not provide further information on these aspects or on event relatedness.

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

The results describe budesonide peak plasma concentrations under four listed regimens in a randomized crossover study of healthy subjects. The posted geometric means range across the regimen summaries, with associated geometric coefficients of variation indicating differing relative dispersion. These observations provide descriptive pharmacokinetic information for the regimens included in the record.

They do not, by themselves, quantify the comparative effect of one regimen relative to another. The registry record does not report adjusted or paired contrasts, confidence intervals, p-values, or an equivalence assessment. Because this is a crossover study, the relationship between each participant's observations across periods is relevant to the precision of a formal contrast; that relationship is not available in the posted summaries. A reader should not interpret differences between the listed means as established treatment effects.

The study is titled as an assessment of relative bioavailability with and without a spacer and oral charcoal. However, the record does not map the four regimen labels to each specific combination of those administration conditions. It is therefore not possible to attribute a particular reported Cmax value to a specific spacer or charcoal condition using the posted regimen descriptions alone. Nor do the primary results establish findings for Tmax, AUC0-∞, or the other listed analytes.

The study's healthy-subject description also defines an important boundary on interpretation. The registry lists Chronic Obstructive Pulmonary Disease as a condition, but the study title and summary identify healthy subjects; the record does not explain the discrepancy. The posted pharmacokinetic summaries should not be treated as evidence about clinical outcomes in people with COPD or about symptom benefit. They address plasma concentration, not clinical effectiveness.

Finally, the safety record reports no serious adverse events and no deaths in the listed entries, with other adverse-event counts also recorded. These results are limited to the registry's entries and do not establish that a regimen is free of risk. Overall, the record supports a descriptive account of the reported pharmacokinetic and safety summaries, while leaving comparative precision, formal inference, and several design details unreported.

13. Why This Trial Matters Statistically

This trial illustrates why pharmacokinetic summaries and treatment comparisons are not interchangeable. A geometric mean can characterize the observed concentration level, and a geometric coefficient of variation can describe relative spread. Neither alone provides the uncertainty around a contrast between regimens. When a registry posts regimen-specific summaries without a comparison estimate or confidence interval, readers can describe the data but cannot assess the precision of the comparative result from those summaries alone.

The crossover structure makes this distinction especially important. Participants receive more than one regimen, so observations within a person are related. A formal analysis can use that structure, but a comparison based only on separate regimen means does not reveal the within-participant relationship. The record identifies a crossover design without posting a crossover model, sequence information, or paired estimates. It thus offers a useful example of how design labels do not substitute for analysis details.

The title's focus on relative bioavailability also highlights the need for clear regimen mapping. The registry identifies four regimen labels and describes test and reference formulations, while the title names spacer and oral-charcoal conditions. Without a complete mapping between labels and conditions, it is difficult to attach a particular summary to a specific administration feature. Clear intervention descriptions are essential for interpreting pharmacokinetic contrasts.

Finally, the record distinguishes an enrollment figure from regimen-level analysis counts but does not explain the participant flow between them. That gap, together with the unreported multiplicity and missing-data methods, limits reproducibility and interpretation. These issues matter statistically because the meaning of a result depends not only on its numerical summary but also on who contributed data, how repeated observations were analyzed, and how uncertainty and multiple comparisons were handled.

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.

Several limitations are specific to the registry information available for this study. First, the four regimen labels are not fully mapped to the combinations of spacer use and oral charcoal described in the official title. The entries identify test formulation as Regimen B or D and reference formulation as Regimen A or C, but do not identify which label corresponds to each administration condition. This prevents regimen-specific interpretation of those conditions.

Second, the primary endpoint is reported only through regimen-specific geometric means and geometric coefficients of variation. Comparative estimates, confidence intervals, p-values, and a formal equivalence assessment are not reported in the registry record. A two-arm comparison is not estimable in the posted outcome, and no single contrast is identified as the basis for a comparative conclusion.

Third, crossover details needed to interpret a formal analysis are limited. The record does not report sequence allocation, washout duration, a statistical model, or results for period or carryover effects. It also does not provide individual-level data or within-participant covariance. These omissions matter because the treatment comparisons in a crossover design depend on the relationship between repeated observations from the same participant.

Fourth, the registry lists 56 enrolled participants and 52 participants for each regimen's primary summary but does not explain the difference. The pharmacokinetic population definition gives general inclusion criteria, but counts and reasons for exclusions, missing samples, or protocol deviations are not reported. The record also leaves the listed COPD condition unreconciled with its description of healthy subjects. These reporting gaps limit assessment of participant flow, analysis-population selection, and the intended population for interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010 — NCT03311373.
• Registry record last updated 2020-06-11; status last verified 2020-06.
• Results first posted 2020-06-11.
• 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

NCT03311373 is a completed, randomized, open-label, Phase 1, single-dose crossover study of PT010 in healthy subjects, with 56 enrolled. The registry lists four regimens and describes a relative-bioavailability objective involving spacer and oral-charcoal conditions. Its primary endpoint is budesonide Cmax, summarized by geometric mean and geometric coefficient of variation for each regimen. Regimen-level participant counts are 52 each. The record posts no inferential analyses for the primary outcome, and formal comparative estimates and their precision are not reported. It lists six secondary outcomes and 12 outcome measures overall. Safety entries record no serious adverse events or deaths, alongside other adverse-event counts for each regimen. Important details—including the regimen-to-condition mapping, statistical model, missing-data handling, and multiplicity plan—are not reported in the registry record.