A Study to Assess the PK and Safety of PT010 in Subjects With COPD Following Single and Repeat Dose: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the PK and Safety of PT010 in Subjects With COPD Following Single and Repeat Dose (NCT03250182), a randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax) - Budesonide.

2. Clinical Question

3. Trial Design

This was a Phase I, open-label study of PT010 in subjects with moderate to severe COPD. The registry lists the study as randomized, with a parallel model and no masking. Its stated aim was to assess pharmacokinetics and safety following single and repeat dosing. The brief summary describes a single treatment period of 8 days, with pharmacokinetic assessment after a single dose on Day 1 and reassessment after 7 days of repeat dosing. Screening could last up to 28 days, and a follow-up phone call was planned at least 5 days but no longer than 7 days after the last dose.

The listed intervention was PT010, an inhaled combination of budesonide, glycopyrrolate, and formoterol fumarate. The arm description says it was administered as 2 inhalations per use as instructed in the protocol. The primary outcome concerned budesonide Cmax on Day 1. Listed secondary pharmacokinetic outcomes include Tmax and AUC from time zero extrapolated to infinity for budesonide, glycopyrronium, and formoterol. The registry lists 21 outcome measures in total, but the record does not provide numerical results for the primary endpoint in the information available for interpretation.

The study started on 2017-08-11, reached primary completion on 2017-12-07, and is recorded as completed. The sponsor is Pearl Therapeutics, Inc. The record describes a single-center study, but does not give additional center details. There is a design-and-results qualification: allocation is labeled randomized, while the primary outcome listing identifies a PT010 group and indicates that fewer than two arms are available for that outcome. The registry record does not explain this discrepancy or provide a comparator result. Consequently, the primary outcome information supports no treatment-group comparison.

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: BGF MDI 320/14.4/9.6 μg oral inhalation as follows: * Single-dose on the morning of Day 1 (Visit 3) followed by serial blood draws for 24 hours * BID dosing every morning and evening on Day 2 through Day 7 approximately 12 hours apart * Single-dose administration on the morning of Day 8 (Visit 5) followed by serial blood draws for 12 hours

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety Population: All subjects who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Plasma Concentration (Cmax) - Budesonide, measured over Day 1.

The primary endpoint is budesonide maximum plasma concentration, or Cmax, on Day 1, expressed in pg/mL. Cmax is the highest measured concentration of a drug in plasma over the relevant sampling period. In pharmacokinetic work, this peak concentration helps describe the concentration profile after dosing. It addresses exposure at the peak, rather than the total exposure over time or the duration of exposure.

The registry specifies that Cmax is summarized by a geometric mean and geometric coefficient of variation. In general, a geometric mean is useful for positive measurements that vary multiplicatively or have a right-skewed distribution. The geometric coefficient of variation describes relative spread on a multiplicative scale; it is not the same as a confidence interval and does not, by itself, communicate uncertainty in the estimated mean. The record does not report the numerical geometric mean, the coefficient of variation, a confidence interval, or an analysis result for this endpoint.

The defined pharmacokinetic population includes treated subjects with sufficient information to calculate at least one pharmacokinetic parameter for at least one analyte and without major protocol deviations affecting pharmacokinetic analysis. That definition matters because it means the endpoint is not necessarily based on every enrolled or treated subject. The number included is not reported in the registry record. Cmax is a pharmacokinetic measure; by itself, it is not a measure of symptom change, lung function, or clinical benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a pharmacokinetic measurement: budesonide Cmax on Day 1. In general, pharmacokinetic measurements describe how drug concentrations change in the body over time. Cmax focuses on the peak concentration observed in the sampling period. Other common measures answer different questions. Tmax is the time at which the peak is reached, while AUC describes exposure accumulated across time. The listed secondary outcomes include Tmax and AUC from time zero extrapolated to infinity for budesonide, glycopyrronium, and formoterol. Their inclusion does not provide their values; those numerical results are not reported in the registry record.

The registry says the primary endpoint was summarized with a geometric mean and geometric coefficient of variation. In general, geometric summaries are appropriate for positive quantities when variation is naturally expressed as proportional changes, or when values are asymmetric on the original scale. A geometric mean summarizes the central level on a multiplicative scale. The geometric coefficient of variation describes relative dispersion around that scale. It should not be read as a confidence interval, a range containing most observations, or a direct statement of the precision of the mean. Interpreting either summary requires the actual reported values and, for uncertainty, an interval or other inferential result. Those are not reported for this endpoint.

The specified analysis population is also important. It includes all treated subjects who had sufficient data to reliably calculate at least one pharmacokinetic parameter for at least one analyte and did not have major protocol deviations affecting pharmacokinetic analysis. This eligibility definition is tied to the availability and usability of pharmacokinetic data. It does not say how many subjects contributed to budesonide Cmax specifically. The endpoint-specific analysis count and the number excluded from the population are not reported in the registry record.

In general, pharmacokinetic data can be incomplete for several reasons, such as unavailable samples or measurements that cannot be used. The appropriate handling depends on the planned analysis and the missingness pattern. The registry record does not report the missing-data method, whether any measurements were excluded, or how missing samples were handled. It also does not provide the sampling schedule or details about concentration measurement. No such details should be inferred from the endpoint title alone.

The record labels the study randomized and parallel, but the primary outcome listing contains only the PT010 group and indicates fewer than two arms for that outcome. A between-group analysis requires a reported comparator and a defined contrast. Neither appears in the posted primary outcome information. There is consequently no basis for describing a treatment difference, or for deriving an unadjusted comparison from the listed primary endpoint. The randomization procedure and its role in the study are not reported in the registry record.

For studies that compare groups, estimates may be accompanied by confidence intervals and hypothesis tests. In general, a confidence interval conveys the range of values reasonably compatible with the data and model, while a p-value assesses compatibility with a specified null hypothesis under those assumptions. These concepts do not supply missing results: no primary endpoint confidence interval, p-value, or test is reported. The registry also gives no statistical analysis plan, model specification, transformation details, or account of any covariate adjustment. The record lists zero analysis entries, so there are no posted primary-outcome analysis records to supplement the endpoint description.

The registry's sample-size assumptions describe a planning illustration based on an observed effect, using 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. Such planning illustrations are not the trial's own design justification and are not observed power. In this study record, the primary outcome lacks a two-arm comparison and a numerical observed effect, so those assumptions cannot be used to interpret a treatment contrast from the primary outcome. The sample-size justification for the trial itself is not reported in the registry record.

Over-dispersion is a general concern when observed variation exceeds what a statistical model assumes. In general, ignoring it can make uncertainty appear too small and inference too confident. That issue cannot be evaluated for this endpoint because the registry does not report individual-level data, a model, or an uncertainty estimate. More broadly, statistical methods are interpretable only in relation to the estimand, analysis population, measurement process, and assumptions. The available description supplies the endpoint and population definition, but not enough detail to assess those other components.

10. Multiplicity, Missing Data and Analysis Populations

The record lists multiple outcomes: a primary budesonide Cmax endpoint on Day 1, secondary Tmax and AUC outcomes for three analytes, and 21 outcome measures overall. When multiple outcomes are tested, the chance of at least one apparently notable result can increase. In general, a prespecified testing hierarchy, multiplicity adjustment, or clear distinction between confirmatory and exploratory outcomes can help readers understand how results should be interpreted. The registry record does not report a multiplicity strategy, a testing hierarchy, or which secondary outcomes were treated as confirmatory. Since numerical results and tests are not reported for the primary endpoint, there is no basis to assess multiplicity-adjusted inference.

The primary pharmacokinetic population is defined by treatment, sufficient data for at least one parameter for at least one analyte, and no major protocol deviations affecting the pharmacokinetic analysis. The number meeting this definition, and the number with evaluable Day 1 budesonide Cmax data, are not reported in the registry record. The handling of missing measurements, unusable samples, or participants who did not contribute to a particular outcome is also not reported. The record does not state whether an imputation method was used or whether analyses relied only on observed measurements.

The registry labels allocation randomized and the model parallel, but the primary outcome listing identifies one PT010 group and fewer than two arms. It does not report the comparison needed to interpret a between-group effect. The randomization procedure, analysis set used for any comparison, and statistical plan are not reported in the registry record. These gaps limit assessment of both multiplicity and missing-data assumptions, and prevent a reader from reconstructing an inferential analysis from the outcome description.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists PT010 with 30 subjects at risk for serious adverse events and 0 affected. It lists 30 at risk for other adverse events and 5 affected. The record also lists 0 deaths. These are counts in the registry's safety categories; they should not be converted into rates or combined into a total. The record does not provide event descriptions for the other adverse events in the information, and no serious adverse-event terms are listed.

In general, a count of affected subjects is not the same as a count of individual events: one subject may experience more than one event. The record does not clarify event-level counts for the other adverse-event category. It also does not provide severity, timing, duration, relatedness assessments, or a comparison group for these counts. The absence of recorded serious events in this summary is not proof that no event occurred outside the registry's reporting scope, and the record does not establish that an event was caused by or unrelated to PT010. Safety counts should therefore be read as descriptive registry entries, not as a comparative safety estimate.

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

The record describes a Phase I study designed to examine pharmacokinetics and safety of PT010 in subjects with moderate to severe COPD. Its primary endpoint is the Day 1 maximum plasma concentration of budesonide, with a geometric mean and geometric coefficient of variation specified as the summary measures. This provides a clear description of the intended measurement and its pharmacokinetic focus. The record also identifies later pharmacokinetic assessments and secondary outcomes concerning peak timing and exposure.

What the record does not provide is the numerical primary endpoint result. Without an estimate or uncertainty measure, the magnitude and precision of Day 1 budesonide Cmax cannot be evaluated. The absent numerical result does not mean the concentration was zero, that the study found no change, or that no analysis was performed. It means the registry record does not report the result needed for those judgments. The record also does not provide numerical findings for the listed secondary outcomes in the registry record for interpretation.

The study should not be read as a comparative test of PT010 against another intervention on the basis of these primary outcome details. The record labels the allocation randomized and the model parallel, but the endpoint result information lists only PT010 and indicates fewer than two arms. There is no reported comparator or primary outcome contrast. Accordingly, no treatment difference can be estimated or interpreted from the posted primary outcome information.

The safety information is similarly descriptive. The record lists no subjects affected in the serious adverse-event category, 5 affected in the other adverse-event category, and 0 deaths. These figures do not establish comparative safety, causal attribution, or the absence of unrecorded events. Overall, the trial record defines a pharmacokinetic and safety assessment, but the numerical efficacy-like or pharmacokinetic findings required to judge endpoint magnitude and precision are not reported. Any broader conclusion would go beyond what the registry record supports.

13. Why This Trial Matters Statistically

This study illustrates why a clearly named endpoint and a numerical result are different kinds of information. The endpoint definition identifies what was intended to be measured: budesonide Cmax on Day 1, in pg/mL, summarized geometrically. That description lets readers understand the pharmacokinetic question. It does not reveal the observed concentration or how much the estimate varied. Without the estimate and an uncertainty measure, readers cannot assess the result's magnitude or precision.

It also highlights the importance of matching the analysis population to the outcome. The stated pharmacokinetic population requires sufficient data for at least one parameter and analyte, as well as no major protocol deviations affecting the analysis. The number in that population is not reported, and the record does not say how many subjects had usable data for the primary endpoint. Enrollment alone cannot answer those questions. Clear reporting of the population contributing to each outcome helps distinguish planned enrollment from actual analysis data.

A further statistical issue is the difference between a randomized label and a reported randomized comparison. The record labels allocation randomized but gives only the PT010 group for the primary outcome and indicates fewer than two arms. A comparative interpretation requires the groups, endpoint values, and contrast to be available. Here, the primary outcome information does not support that type of inference. It is therefore important not to treat randomization status as a substitute for a reported comparator result.

Finally, listed outcomes and planning assumptions should not be confused with findings. The registry names secondary pharmacokinetic measures and gives assumptions for planning illustrations, but it does not report the primary numerical endpoint result or a test. Planning calculations are not evidence of observed precision or observed power. This distinction is useful in reading early-phase records, where design descriptions can be more complete than posted quantitative outcome reporting.

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 main trial-specific limitation for statistical interpretation is the absence of numerical primary endpoint results. Although the record defines budesonide Cmax on Day 1 and the summary measures, it gives no estimate, geometric coefficient of variation, confidence interval, or test result. The stated outcome therefore cannot be evaluated quantitatively. The record also does not provide numerical values for the named secondary pharmacokinetic outcomes.

The primary pharmacokinetic population is described, but its size is not reported. Nor is the number with evaluable budesonide measurements, the number of samples contributing to the endpoint, or the handling of missing or unusable measurements. This limits assessment of the amount and completeness of data underlying the intended estimate. The registry record does not give the sampling schedule, concentration assay details, or further rules for determining usable measurements.

The record labels allocation randomized and a parallel model, yet the primary outcome information lists PT010 and indicates fewer than two arms. It does not explain the relationship between the randomized design and the one-group primary outcome listing, or identify a comparator result. As a result, neither a group contrast nor the role of randomization in the reported endpoint can be assessed. The statistical analysis plan, model details, interim analyses, and sample-size justification for the study are not reported in the registry record.

Safety reporting is limited to category counts. The record does not supply detailed descriptions, event-level counts, severity, timing, relatedness, or comparison data for the other adverse events. The available counts cannot establish causation or comparative safety. These limitations concern what the registry record reports; they do not establish that the underlying study did not collect additional information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Assess the PK and Safety of PT010 in Subjects With COPD Following Single and Repeat Dose — NCT03250182.
• Registry record last updated 2021-01-29; status last verified 2021-01.
• Results first posted 2020-05-08.
• 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 completed Phase I, open-label study of PT010 in subjects with moderate to severe COPD. It lists randomized allocation, a parallel model, and an enrollment of 30. The stated objective was pharmacokinetic and safety assessment after single and repeat dosing. The primary endpoint was budesonide maximum plasma concentration on Day 1, summarized by geometric mean and geometric coefficient of variation. Secondary outcomes include Tmax and AUC from time zero extrapolated to infinity for budesonide, glycopyrronium, and formoterol.

The primary pharmacokinetic population is defined by treatment, sufficient data for at least one parameter and analyte, and no major protocol deviations affecting the pharmacokinetic analysis. The record does not report the numerical primary endpoint result, its uncertainty, or the size of that analysis population. The primary outcome listing contains PT010 and indicates fewer than two arms, so a comparator result is not available. Safety entries list 0 affected in the serious adverse-event category, 5 affected in the other category, and 0 deaths. These data are descriptive and do not support a comparative treatment conclusion.