This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study to Assess Efficacy and Safety of PT009 Compared to PT005, PT008, and Symbicort® Turbuhaler® on Lung Function Over 24-Weeks in Subjects With Moderate to Very Severe COPD (NCT02766608), a randomized phase 3 study. The primary outcome is Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI Versus FF MDI).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02766608 |
| Phase | Phase 3 |
| Condition | Chronic Obstructive Pulmonary Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 2389 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Pearl Therapeutics, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants had moderate to very severe chronic obstructive pulmonary disorder. The registry record lists 2389 participants enrolled and identifies the primary endpoint population as mITT. The criteria used to define mITT are not reported in the registry record.
Intervention
The study included BFF MDI 320/9.6 μg and BFF MDI 160/9.6 μg. Both were described as budesonide and formoterol fumarate inhalation aerosols administered as two inhalations twice daily. The record also lists formoterol fumarate and budesonide inhalers as separate regimens.
Comparator
The primary question names BFF MDI versus FF MDI 9.6 μg. The study also included BD MDI 320 μg and open-label Symbicort Turbuhaler 400/12 μg as an active control. The reported primary endpoint estimates cover the two BFF regimens and FF MDI.
Primary question
At Week 24, how did morning pre-dose trough FEV1 change from baseline in the mITT population? The endpoint is measured in liters. Although the primary question names a BFF-versus-FF comparison, the registry record reports least-squares mean changes and confidence intervals by arm, not an estimate or test for that direct contrast.
3. Trial Design
This was a Phase III, randomized, double-blind, parallel-group, multicenter study with a 24-week treatment period. The registry record describes quadruple masking. Symbicort Turbuhaler was identified as an open-label active control, so the open-label status applies to that comparator as described in the record; further details about how masking was implemented across study roles are not reported in the registry record.
The study enrolled 2389 participants with moderate to very severe COPD. The five listed regimens were BFF MDI 320/9.6 μg, BFF MDI 160/9.6 μg, FF MDI 9.6 μg, BD MDI 320 μg, and Symbicort Turbuhaler 400/12 μg twice daily. The intervention descriptions specify two inhalations twice daily for each regimen. The primary endpoint compared BFF MDI with FF MDI and was assessed at Week 24. Additional outcomes addressed exacerbations, lung function, rescue inhaler use, time to onset, and health status.
Randomization and a parallel-group structure allow the study to compare outcomes across concurrently assigned treatment groups, while masking is intended to reduce some sources of knowledge-related bias. These are general design principles; the registry record does not give the randomization procedure, allocation concealment details, or methods used to maintain masking. It also does not report the planned sample-size justification, the target enrollment for each arm, or interim analyses. The listed total enrollment should not be interpreted as the number analyzed for every outcome: the primary endpoint has arm-specific analysis counts, and those counts differ from the overall enrollment.
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: Subjects were randomized in a 3:3:3:1:1 ratio to BFF 320/9.6, BFF 160/9.6, FF 9.6, BD 320, and Symbicort.
Overall Study
| Stage | BFF MDI 320/9.6 μg | BFF MDI 160/9.6 μg | FF MDI 9.6 μg | BD MDI 320 μg | Symbicort TBH 400/12 μg |
|---|---|---|---|---|---|
| STARTED | 655 | 637 | 644 | 206 | 219 |
| COMPLETED | 576 | 567 | 554 | 169 | 190 |
| NOT COMPLETED | 79 | 70 | 90 | 37 | 29 |
Reasons for not completing this period:
| Reason | BFF MDI 320/9.6 μg | BFF MDI 160/9.6 μg | FF MDI 9.6 μg | BD MDI 320 μg | Symbicort TBH 400/12 μg |
|---|---|---|---|---|---|
| Adverse Event | 27 | 22 | 17 | 13 | 12 |
| Withdrawal by Subject | 21 | 20 | 24 | 13 | 10 |
| Lack of Efficacy | 16 | 15 | 32 | 8 | 2 |
| Lost to Follow-up | 6 | 3 | 5 | 2 | 2 |
| Physician Decision | 3 | 2 | 3 | 1 | 2 |
| Protocol disc criteria | 3 | 3 | 4 | 0 | 0 |
| Protocol Violation | 0 | 4 | 4 | 0 | 1 |
| Administrative Reasons | 3 | 1 | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: mITT
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: The Modified Intent-To-Treat (mITT) Population is a subset of the ITT Population, and is defined as all subjects with post-randomization data obtained prior to discontinuation from treatment. The Intent-To-Treat (ITT) Population is defined as all subjects who were randomized to treatment and received any amount of the study treatment.
| Characteristic | Unit | BFF MDI 320/9.6 μg | BFF MDI 160/9.6 μg | FF MDI 9.6 μg | BD MDI 320 μg | Symbicort TBH 400/12 μg | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 664 | 649 | 648 | 209 | 219 | 2389 | |
| Age, Continuous | Years | 64.2 (SD 7.7) | 64.3 (SD 7.6) | 64.1 (SD 8.0) | 64.2 (SD 7.4) | 65.3 (SD 7.0) | 64.3 (SD 7.7) |
| Sex: Female, Male: Values listed are mITT population – Female | Participants | 253 | 260 | 261 | 81 | 78 | 933 |
| Sex: Female, Male: Values listed are mITT population – Male | Participants | 402 | 377 | 383 | 125 | 141 | 1428 |
| Ethnicity (NIH/OMB): Values listed are mITT population – Hispanic or Latino | Participants | 16 | 18 | 21 | 8 | 6 | 69 |
| Ethnicity (NIH/OMB): Values listed are mITT population – Not Hispanic or Latino | Participants | 637 | 616 | 623 | 198 | 212 | 2286 |
| Ethnicity (NIH/OMB): Values listed are mITT population – Unknown or Not Reported | Participants | 2 | 3 | 0 | 0 | 1 | 6 |
| Race (NIH/OMB): Values listed are mITT population – American Indian or Alaska Native | Participants | 2 | 2 | 2 | 0 | 0 | 6 |
| Race (NIH/OMB): Values listed are mITT population – Asian | Participants | 1 | 1 | 0 | 0 | 1 | 3 |
| Race (NIH/OMB): Values listed are mITT population – Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Values listed are mITT population – Black or African American | Participants | 19 | 15 | 20 | 9 | 8 | 71 |
| Race (NIH/OMB): Values listed are mITT population – White | Participants | 633 | 619 | 622 | 197 | 210 | 2281 |
| Race (NIH/OMB): Values listed are mITT population – More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Values listed are mITT population – Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI Versus FF MDI), measured over at Week 24.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Liter |
| Endpoint classification | Continuous Endpoint |
Forced expiratory volume in one second, or FEV1, is the volume of air exhaled during the first second of a forced expiration. The primary endpoint is the change from baseline in morning pre-dose trough FEV1 at Week 24, measured in liters. A pre-dose trough measurement is taken before a scheduled dose, so it describes lung function at that point in the dosing schedule rather than the peak response after inhalation.
Change from baseline expresses the endpoint relative to each participant’s starting measurement. The reported arm summaries are least-squares means, which are model-based estimates rather than simple arithmetic averages. Their confidence intervals describe uncertainty around each arm’s estimated mean change. The registry record does not specify the statistical model, covariates, or method used to construct these estimates.
FEV1 is used in respiratory trials as an objective measure of lung function. As a general statistical point, an objective continuous endpoint can summarize changes across participants on a common measurement scale. It does not, by itself, describe every aspect of COPD or establish how a measured change relates to symptoms, daily functioning, or longer-term outcomes. The primary endpoint is therefore one component of the study’s assessment, alongside the other outcomes named in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the primary endpoint, the registry record reports least-squares mean change from baseline at Week 24 for three arms. The estimate for BFF MDI 320/9.6 μg was 0.036 liters, with a 95% confidence interval from 0.019 to 0.053. For BFF MDI 160/9.6 μg, the estimate was 0.017 liters, with a 95% confidence interval from 0.0 to 0.034. For FF MDI 9.6 μg, the estimate was -0.003 liters, with a 95% confidence interval from -0.02 to 0.015. The analysis counts were 571, 564, and 550, respectively.
These are arm-level estimates of change, not estimates of the difference between BFF and FF. The primary question names a BFF-versus-FF comparison, but the registry record does not report the contrast estimate, its confidence interval, or a p-value for that primary comparison. The arm-level confidence intervals must not be treated as if they were confidence intervals for a between-arm difference. In general, comparing whether separate arm intervals overlap is not a substitute for estimating and testing the contrast directly.
The intervals describe the precision of the estimated mean changes under the analysis used. They do not show the range of individual participant responses. Nor do the point estimates alone establish the size or precision of a treatment contrast. Because the direct primary comparison is not reported, the posted primary results support a description of the arm-specific changes but not a complete statistical interpretation of the named contrast.
The registry record identifies the primary population as mITT but does not define its membership or explain how participants with missing Week 24 measurements were handled. The listed analysis counts therefore describe the reported primary endpoint summaries, not necessarily the reasons why some enrolled participants are absent from those summaries. Information about the analysis model and any adjustment for baseline or other variables is also not reported in the registry record. These gaps limit assessment of how the arm estimates were obtained and how robust they are to analytic choices.
Overall, the primary endpoint results indicate the posted estimated mean changes within the reported arms. They do not provide the comparative estimate needed to quantify the difference between BFF MDI and FF MDI. A reader should keep that distinction in mind when interpreting the primary results.
9. Statistical Methods Explained
What a least-squares mean represents. The primary results are reported as least-squares means. In general, a least-squares mean is an estimate produced by a statistical model, often adjusted for variables included in that model. It is not necessarily the unadjusted arithmetic average of the observed participant changes. The registry record does not report the model specification, the variables included, or whether the estimates were adjusted. As a result, the precise interpretation of the adjustment cannot be established from the record alone.
What the confidence intervals describe. A confidence interval conveys the statistical uncertainty around an estimated quantity under the assumptions of the analysis. Here, the intervals accompany arm-level estimates of mean change in FEV1. They should be read as intervals for those arm estimates, not as intervals for the difference between arms. The registry record does not give a confidence interval for the named BFF-versus-FF primary contrast. General statistical guidance: an interval that is narrower indicates greater precision for the estimate it surrounds, while an interval that is wider indicates more uncertainty. Neither an interval nor its endpoints give the distribution of individual participants’ changes.
Why the contrast matters. A treatment comparison is usually expressed as a difference between groups, with an estimate and an uncertainty interval for that difference. This directly addresses how far apart the groups’ estimated outcomes are, while accounting for uncertainty in the comparison. The arm means alone do not supply that contrast. It is not appropriate to derive a new comparative estimate from these posted summaries because the registry record provides neither the required analysis details nor a recalculated primary comparison. The sponsor’s own analysis does not take precedence on this outcome in the registry entries, since no discrepancy is identified; however, a sponsor comparison is also not reported in the registry record.
Continuous outcomes and variability. FEV1 change is a continuous measure: it can take a range of values rather than being limited to categories such as yes or no. Continuous outcomes are commonly summarized with a mean and a measure of uncertainty. In general, the mean describes the center of the group’s measurements, while variation among participants affects how precisely that mean is estimated. The primary result reports confidence intervals, not standard deviations or standard errors. The registry record does not provide a distributional summary that would show how widely individual changes varied.
Missing data and analysis populations. The primary population is labeled mITT, but the registry record does not describe which randomized participants were included, whether membership depended on treatment received or available measurements, or how missing outcome values were handled. General statistical point: if outcome availability is related to participants’ outcomes or treatment assignment, analyzing only observed measurements may affect interpretation. Methods such as imputation or likelihood-based approaches can address missingness under specified assumptions, but no such method is reported in the registry record. It is therefore not possible to assess the missing-data assumptions or their potential influence on the primary estimate.
Unadjusted secondary comparisons. The posted SGRQ comparison results include unadjusted p-values. An unadjusted p-value addresses a particular comparison without accounting for the fact that multiple outcomes or comparisons may have been examined. General statistical point: when many hypotheses are tested, the chance of at least one apparently notable result can increase. Adjustment strategies or a prespecified hierarchy can help control that issue, but the registry record does not report a multiplicity plan. The listed p-values should therefore be interpreted as unadjusted results rather than as evidence that an overall family of outcomes has been tested at a controlled error rate.
Planning illustrations. The sample-size illustrations use the observed effect as their starting point and are explicitly not the trial’s own design calculation. They are described as two-sided, with a significance level of 0.05, equal allocation between two arms, and a normal approximation; the illustrated effect is a stated fraction of the observed effect. These figures are planning illustrations, not observed power and not evidence about the probability that the completed study detected an effect. The registry record does not report the original sample-size assumptions or justification, so the illustrations cannot be used to reconstruct the trial’s design rationale.
Multiplicity, interim looks, and model checks. The registry record does not report an interim analysis plan, stopping rules, model diagnostics, sensitivity analyses, or a strategy for managing multiple primary comparisons. Such details matter because they clarify how the analysis was selected and how uncertainty was assessed. Their absence from the registry record does not show that the procedures were not performed; it means they are not documented in the available record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record names one primary endpoint and multiple secondary outcomes, but it does not report a statistical analysis plan describing how the primary and secondary hypotheses were prioritized. It also does not report whether the study used a hierarchy, a family-wise adjustment, or another approach to account for multiple comparisons. Without that information, the inferential status of the secondary findings is uncertain. The unadjusted p-values reported for the available secondary comparisons should be read as results for individual comparisons, not as multiplicity-controlled evidence across all outcomes.
Missing-data procedures are not reported in the registry record. There is no description of how participants without a Week 24 measurement were handled, whether any values were imputed, or what assumptions were used. The record labels the primary population mITT but does not state the membership criteria. It is also not clear from the record whether all randomized participants were included in each secondary analysis or how the analysis populations differed by outcome. The reported analysis counts give the number associated with the primary arm summaries, but not a full account of missingness or participant flow.
These omissions restrict assessment of possible bias from incomplete outcome data and make it harder to reproduce the reported estimates. As a general point, the impact of missing data depends not only on how many measurements are absent but also on why they are absent and how that relates to treatment and outcome. No conclusion about the direction or magnitude of any such impact can be drawn from the registry record.
The record also does not report interim analyses, stopping boundaries, or a detailed prespecified model. The registry lists zero formal posted analysis entries, although outcome results are present. This does not establish what analyses were conducted outside the registry; it indicates that detailed analysis documentation is not available in the registry record. These limitations warrant caution when interpreting precision, confirmatory status, and reproducibility.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| BFF MDI 320/9.6 μg | 42 | 655 | 6.4% |
| BFF MDI 160/9.6 μg | 45 | 637 | 7.1% |
| FF MDI 9.6 μg | 72 | 644 | 11.2% |
| BD MDI 320 μg | 15 | 206 | 7.3% |
| Symbicort TBH 400/12 μg | 20 | 219 | 9.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BFF MDI 320/9.6 μg | 3 of 655 |
| BFF MDI 160/9.6 μg | 2 of 637 |
| FF MDI 9.6 μg | 2 of 644 |
| BD MDI 320 μg | 0 of 206 |
| Symbicort TBH 400/12 μg | 2 of 219 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BFF MDI 320/9.6 μg | 240 of 655 |
| BFF MDI 160/9.6 μg | 201 of 637 |
| FF MDI 9.6 μg | 219 of 644 |
| BD MDI 320 μg | 75 of 206 |
| Symbicort TBH 400/12 μg | 57 of 219 |
Most frequent serious adverse event terms
| Event term | Organ system | BFF MDI 320/9.6 μg | BFF MDI 160/9.6 μg | FF MDI 9.6 μg | BD MDI 320 μg | Symbicort TBH 400/12 μg |
|---|---|---|---|---|---|---|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 15 of 655 | 10 of 637 | 29 of 644 | 2 of 206 | 6 of 219 |
| Pneumonia | Infections and infestations | 4 of 655 | 5 of 637 | 6 of 644 | 0 of 206 | 3 of 219 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 655 | 2 of 637 | 4 of 644 | 0 of 206 | 1 of 219 |
| Atrial fibrillation | Cardiac disorders | 1 of 655 | 5 of 637 | 2 of 644 | 1 of 206 | 0 of 219 |
| Cardiac failure congestive | Cardiac disorders | 1 of 655 | 1 of 637 | 1 of 644 | 2 of 206 | 1 of 219 |
| Acute myocardial infarction | Cardiac disorders | 0 of 655 | 2 of 637 | 2 of 644 | 0 of 206 | 0 of 219 |
| Angina pectoris | Cardiac disorders | 1 of 655 | 2 of 637 | 1 of 644 | 0 of 206 | 0 of 219 |
| Ischaemic stroke | Nervous system disorders | 0 of 655 | 1 of 637 | 2 of 644 | 0 of 206 | 1 of 219 |
| Angina unstable | Cardiac disorders | 0 of 655 | 2 of 637 | 1 of 644 | 0 of 206 | 0 of 219 |
| Atrial flutter | Cardiac disorders | 1 of 655 | 0 of 637 | 1 of 644 | 1 of 206 | 0 of 219 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BFF MDI 320/9.6 μg | BFF MDI 160/9.6 μg | FF MDI 9.6 μg | BD MDI 320 μg | Symbicort TBH 400/12 μg |
|---|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 40 of 655 | 40 of 637 | 43 of 644 | 17 of 206 | 14 of 219 |
| Upper respiratory tract infection | Infections and infestations | 25 of 655 | 21 of 637 | 20 of 644 | 5 of 206 | 3 of 219 |
| Chronic obstructive pulmonary disease | Infections and infestations | 16 of 655 | 10 of 637 | 30 of 644 | 2 of 206 | 6 of 219 |
| Hypertension | Vascular disorders | 14 of 655 | 22 of 637 | 15 of 644 | 5 of 206 | 4 of 219 |
| Back pain | Musculoskeletal and connective tissue disorders | 18 of 655 | 13 of 637 | 18 of 644 | 3 of 206 | 2 of 219 |
| Headache | Nervous system disorders | 19 of 655 | 8 of 637 | 15 of 644 | 3 of 206 | 1 of 219 |
| Cough | Respiratory, thoracic and mediastinal disorders | 7 of 655 | 15 of 637 | 15 of 644 | 7 of 206 | 0 of 219 |
| Oral candidiasis | Infections and infestations | 17 of 655 | 14 of 637 | 5 of 644 | 3 of 206 | 3 of 219 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 12 of 655 | 11 of 637 | 9 of 644 | 7 of 206 | 3 of 219 |
| Bronchitis | Infections and infestations | 16 of 655 | 7 of 637 | 10 of 644 | 4 of 206 | 2 of 219 |
Serious events with the highest arm-level rate: chronic obstructive pulmonary disease (4.5%), pneumonia (1.4%), cardiac failure congestive (1.0%), pancreatitis acute (0.9%), atrial fibrillation (0.8%).
The registry record lists serious adverse events by treatment group, with the number at risk and the number affected. It also reports deaths by group. These are descriptive counts; no comparative statistical analysis, confidence intervals, or adjustment for differences in follow-up are reported. The group sizes are not equal, so the counts alone should not be read as direct comparisons of risk. No rates should be inferred from the counts without an appropriate analysis and clear information about the relevant denominators and follow-up.
The record lists chronic obstructive pulmonary disease, pneumonia, congestive cardiac failure, acute pancreatitis, atrial fibrillation, and acute respiratory failure among the leading serious-event terms, with percentages reported for those terms. The record does not provide arm-specific results for those terms in the registry entries, so they cannot be attributed to a particular treatment group from this information. It is also not reported whether the percentages represent participants, events, or another denominator.
These figures describe serious adverse events recorded during the study, not a complete safety comparison or an assessment of causality. The registry record does not report statistical tests comparing groups for these outcomes. The reported deaths are counts and should not be interpreted as establishing a treatment-related cause.
12. What the Result Does, and Does Not, Mean
The primary results describe estimated mean changes in morning pre-dose trough FEV1 within three treatment groups at Week 24. The estimates have associated confidence intervals, which communicate uncertainty around those arm-level changes. They do not, by themselves, quantify the difference between BFF MDI and FF MDI. Since the registry record does not report the direct primary contrast, the posted data do not provide a complete statistical answer to the stated primary comparison.
The results also do not describe every participant’s response. A group mean can conceal a range of individual outcomes, and the confidence interval around a mean is not an interval containing most individual values. The registry record does not include the distribution of individual changes or other information needed to assess variation in response.
The secondary outcomes address distinct questions, but numerical results are not reported for most of them in the registry record. The available secondary comparison is unadjusted, and no multiplicity strategy is reported. It should therefore be viewed as one result among multiple outcome questions rather than as definitive evidence across the study’s outcome set.
These statistics do not establish a clinical benefit or lack of benefit, do not show that one regimen is preferable for an individual, and do not settle safety comparisons. They are limited to the outcomes, populations, and analyses documented in the registry record. The trial’s duration was 24 weeks, so the reported study period does not itself provide information about outcomes beyond that treatment period. The sample-size illustrations are planning calculations based on observed effects, not observed power and not the original justification for enrollment.
The most defensible reading is therefore descriptive: the record reports arm-specific primary endpoint estimates and some secondary and safety data, while leaving important comparative and analytic details unreported. Those gaps limit how far the results can be extended beyond the reported summaries.
13. Why This Trial Matters Statistically
This trial is statistically notable because it combines a large randomized, parallel-group design with several active treatment regimens and multiple outcome domains. Randomization can support comparisons among assigned groups, while the parallel structure allows outcomes to be assessed across groups over the same treatment period. The registry record describes double-blind design and quadruple masking, alongside an open-label active control, illustrating why the details of masking and outcome-specific procedures matter when interpreting clinical trial results.
The primary endpoint is continuous and is reported using least-squares mean changes with confidence intervals. That format emphasizes both the estimated direction and the precision of arm-level results. Yet the primary question is comparative, and the record does not provide the estimate for the named BFF-versus-FF contrast. This distinction is central to sound statistical reporting: arm summaries can be informative, but a comparison requires its own estimate and uncertainty measure.
The secondary outcome set spans lung function, exacerbations, health status, and rescue inhaler use. Such breadth can provide a more rounded assessment of what a trial measures, but it also creates a multiplicity question. Without a documented plan for prioritizing outcomes and interpreting unadjusted comparisons, isolated secondary findings warrant more cautious interpretation.
Finally, the gap between overall enrollment and outcome-specific analysis counts highlights the importance of transparent population definitions and missing-data methods. The registry record does not explain the analysis population criteria or missing-data handling. These are not minor technicalities: they affect reproducibility and how confidently readers can interpret estimates. The trial therefore illustrates why complete reporting of contrasts, analysis populations, multiplicity procedures, and missing-data assumptions is essential alongside numerical results.
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 limitation for interpreting the primary outcome is that the registry record reports arm-level least-squares mean changes but not the estimated BFF-versus-FF difference, confidence interval, or p-value. The named primary comparison is therefore not directly quantified in the posted results. The registry record also does not describe the statistical model, covariate adjustment, or method used to calculate the confidence intervals.
Primary endpoint results are listed for three arms, while the trial includes five treatment regimens. Primary results for BD MDI and Symbicort Turbuhaler are not reported in the registry record. The record gives an overall enrollment figure and separate outcome analysis counts but does not explain the participant flow between enrollment and each analysis. mITT is named as the primary population, but its definition and membership rules are not reported.
Numerical results for most listed secondary outcomes are not reported in the registry record. The available secondary comparison results include unadjusted p-values, but a multiplicity strategy is not reported. The analysis plan, missing-data methods, interim analyses, model checks, and sensitivity analyses are also not reported. These omissions make it difficult to assess reproducibility and the robustness of the findings.
For safety, the record provides serious adverse event counts and deaths by group, along with leading serious-event terms and percentages. It does not report comparative tests or arm-specific estimates for those leading terms. The meaning of the listed percentages and their denominators is not specified in the available record. These limitations prevent a full comparative interpretation of the safety information.
Finally, the study reports a 24-week treatment period. Longer-term outcomes are not reported in the registry record. The sample-size illustrations are based on observed effects and are not the study’s original design justification, which is also not reported.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Assess Efficacy and Safety of PT009 Compared to PT005, PT008, and Symbicort® Turbuhaler® on Lung Function Over 24-Weeks in Subjects With Moderate to Very Severe COPD — NCT02766608.
- Registry record last updated 2019-09-24; status last verified 2019-07.
- Results first posted 2019-09-24.
- 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.
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18. Record Summary
The registry record describes a completed Phase III randomized, double-blind, parallel-group study of five inhaled regimens in participants with moderate to very severe COPD. The treatment period was 24 weeks, and total enrollment was 2389. The primary outcome was change from baseline in morning pre-dose trough FEV1 at Week 24 in the mITT population.
Arm-level least-squares mean changes and 95% confidence intervals are reported for two BFF regimens and FF MDI. A direct estimate for the named primary comparison is not reported in the registry record. The record lists secondary outcomes across lung function, exacerbation, rescue use, and health status domains, but numerical results for most are not reported. It also lists serious adverse event counts and deaths by group.
The analysis plan, multiplicity strategy, missing-data methods, mITT definition, and original sample-size justification are not reported in the registry record. These gaps limit comparative interpretation and assessment of robustness.