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 Glycopyrronium and Formoterol Fumarate (GFF) Metered Dose Inhaler (MDI) Dose Indicator Study in Adults With Moderate to Very Severe COPD (NCT02268396), a na phase 3 study. The primary outcome is Dose Indicator Actuation Consistency: Percentage of Devices in Agreement Between CRF-Based Dose Indicator Actuation Count.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02268396 |
| Phase | Phase 3 |
| Condition | COPD |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 138 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pearl Therapeutics, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled adults with moderate to very severe chronic obstructive pulmonary disease (COPD). The registry record identifies the analysis population for the primary outcome as the ITT Population. Enrollment was 138. The record does not provide further detail about participant characteristics or describe how the ITT Population was defined, so those details are not reported in the registry record.
Intervention
Participants received the Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI), identified in the record as PT003. The study evaluated the accuracy, reliability and functionality of its dose indicator over a 4-week Treatment Period. The primary measure concerns the indicator’s recorded actuation count; it is not described as a comparison of clinical outcomes between different treatments.
Comparator
This was a single-group study, with allocation listed as NA and masking listed as none. It therefore does not have a separate randomized comparator group. Instead, the primary measure compares the device count with a subject-reported actuation count at the last available visit. Other listed measures compare device counts with counts based on a case report form or device weight. These are measurement references, not treatment-control groups.
Primary question
The primary question is what percentage of devices had agreement between the CRF-based dose indicator actuation count and the subject-reported actuation count at the last available visit in the ITT Population. The measure is specified over the life of the canister, or 120 puffs, up to 4 weeks. The registry record names this endpoint but does not report its observed percentage, the number of devices in agreement, or a confidence interval. Consequently, the degree of agreement and its precision are not reported in the registry record.
3. Trial Design
This was an open-label, multi-center, Phase 3 study in adults with moderate to very severe COPD. The registry record lists a single-group model and no masking. Allocation is listed as NA, consistent with the record’s description of a study without a randomized treatment comparison. Enrollment was 138. The record identifies one intervention: Glycopyrronium and Formoterol Fumarate Metered-dose Inhaler, also named GFF MDI and PT003.
The study’s stated purpose was to evaluate the accuracy, reliability and functionality of the inhaler’s dose indicator. The treatment period was 4 weeks. The primary endpoint is described over the life of the canister, or 120 puffs, up to 4 weeks, and uses the last available visit. The registry record gives the start as 2014-11, the primary completion as 2015-01, and the status as completed.
The design focuses on agreement among actuation counts rather than a difference in clinical outcomes between treatment groups. The primary measure compares a CRF-based dose indicator count with a subject-reported actuation count. The listed secondary measures include comparisons involving eCRF-based, laboratory-advanced, subject-reported and weight-based counts, as well as measures of undercounting and correct advances. These measures address different ways the dose indicator’s count may be evaluated; they do not create a separate control arm.
The registry record does not report details such as the sites, eligibility criteria beyond the stated COPD severity, visit schedule, device-handling procedures or a statistical analysis plan. Those design details are not reported in the registry record, so the study conduct beyond the stated features cannot be characterized from this record.
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: Study was an open-label, multi center study to evaluate the accuracy, reliability, and functionality of GFF MDI dose indicator in adult subjects with moderate to very severe COPD over a 4-week treatment period.
Overall Study
| Stage | GFF MDI (PT003) |
|---|---|
| STARTED | 138 |
| COMPLETED | 126 |
| NOT COMPLETED | 12 |
Reasons for not completing this period:
| Reason | GFF MDI (PT003) |
|---|---|
| Adverse Event | 3 |
| Administrative | 2 |
| Withdrawal by Subject | 1 |
| Lost to Follow-up | 2 |
| Protocol-Specified Criteria | 2 |
| 2 Subjects no Day 29 Assessment | 2 |
Analysis population for the primary outcome, as defined in the registry: ITT 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.
Population: 126 received treatment on Day 1 and 29, 10 prematurely discontinued, 2 with no assessment on Day 29.
| Characteristic | Unit | GFF MDI (PT003) |
|---|---|---|
| Participants analysed | 138 | |
| Age, Continuous | Years | 62.1 (SD 8.3) |
| Gender: Female | Participants | 68 |
| Gender: Male | Participants | 70 |
6. Primary Endpoint
The registry lists the primary outcome as Dose Indicator Actuation Consistency: Percentage of Devices in Agreement Between CRF-Based Dose Indicator Actuation Count, measured over Over the life of the canister/120 puffs - up to 4 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of devices in agreement between the CRF-based dose indicator actuation count and the subject-reported actuation count at the last available visit. It is specified for the ITT Population and over the life of the canister, or 120 puffs, up to 4 weeks. In practical statistical terms, the endpoint summarizes how often the two specified counts meet the study’s definition of agreement. The registry record does not state the numerical tolerance or other operational rule used to classify agreement.
A percentage is useful for expressing agreement as a share of the devices assessed, rather than as a raw count alone. It can make the frequency of agreement easier to interpret, but its meaning depends on the denominator and the classification rule. Those details, including the number of devices evaluated and the observed percentage, are not reported in the registry record.
Agreement is a measurement property: it asks whether two counts are sufficiently alike under a specified rule. It is not the same as correlation, which concerns how values vary together, and it is not a direct measure of a clinical outcome. The endpoint is relevant to evaluating the dose indicator’s counting consistency, but without the result and its precision, the extent of agreement cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a device-count agreement endpoint but does not report its observed value. It gives no percentage of devices in agreement, number of devices meeting the agreement criterion, confidence interval, or statistical test result. The central statistical finding for the primary endpoint is therefore not reported in the registry record. It is not possible to describe whether agreement was high or low, or how precisely it was estimated.
The study’s single-group design matters for interpretation. The primary comparison is between two ways of counting actuations, not between randomized groups receiving different treatments. The record therefore does not support a treatment-effect comparison. Its stated focus is the dose indicator’s accuracy, reliability and functionality, as assessed through count-based outcomes. The record does not report a clinical outcome comparison that would establish an effect on COPD symptoms or other patient outcomes.
The primary endpoint refers to the ITT Population and the last available visit. These labels identify the intended population and timepoint for the measure, but the registry record does not define the ITT Population, state how many devices contributed to the analysis, or explain how missing or incomplete counts were handled. A last-available-visit measure can depend on which observations are available, so those omissions limit assessment of the endpoint’s denominator and potential data-selection effects.
Several other count-agreement or dose-indicator outcomes are listed, including measures using eCRF-based, laboratory-advanced, subject-reported and weight-based counts. The record lists six outcome measures in total, but does not report numerical results for these outcomes. It also lists zero analyses. Thus, the available record does not allow a comparison of results across the different counting references or an assessment of whether any discrepancies were concentrated in a particular outcome definition.
For interpretation, the distinction between naming a measure and reporting its result is essential. The endpoint description tells readers what was intended to be assessed; it does not establish the observed level of device agreement. Without an estimate and an uncertainty measure, neither the magnitude nor precision of the endpoint can be evaluated. Any sample-size figures described as planning illustrations should likewise be read as planning scenarios, not as evidence about the observed result or its power.
9. Statistical Methods Explained
What does an agreement percentage describe?
In general, an agreement percentage expresses the share of evaluated items that satisfy a stated agreement rule. In this study, the primary measure concerns devices and compares a CRF-based dose indicator actuation count with a subject-reported count. The percentage is meaningful only in relation to the rule for classifying counts as in agreement and the set of devices included in the calculation. The registry record does not report the operational agreement threshold, the number of devices in the primary analysis, or the observed percentage.
Agreement and correlation answer different questions. In general, two measures can move together while differing systematically, so a correlation alone does not establish that their values are close. An agreement assessment instead depends on how differences between measurements are judged. The record’s endpoint is explicitly framed as agreement, but it does not report the numerical rule or analysis details needed to reconstruct that assessment.
Why do the counting references matter?
The listed outcomes use several reference sources: subject reports, case report forms, eCRF-based counts, laboratory-advanced counts and weight-based counts. In general, comparing a device indicator with more than one reference can help describe whether conclusions depend on how actuation counts are obtained. But each comparison has its own measurement context and possible sources of discrepancy. These comparisons should not be treated as interchangeable estimates unless their definitions and procedures support that interpretation. Those procedural details are not reported in the registry record.
The secondary outcomes also include the percentage of devices where the indicator count is >20 less than the subject-reported count, described as undercounting, and a measure of correct advances within stated tolerances of ±2 or ±4 actuations. These are distinct classifications, not simply alternate names for the primary agreement endpoint. The registry record does not report the observed results for these measures.
How should uncertainty be considered?
In general, a confidence interval describes a range of values compatible with the data and statistical model at a stated confidence level. Its width conveys precision: wider intervals indicate less precision, while narrower intervals indicate greater precision under the model. A percentage without an uncertainty measure can be difficult to evaluate, especially when the number of assessed devices is not known. No confidence interval for the primary endpoint is reported in the registry record.
For a percentage, precision depends in part on how many observations contribute and on how the observations are distributed. If observations are not independent—for example, if multiple measurements come from the same device or participant—methods that treat every measurement as independent may understate uncertainty. This is a general statistical consideration, not a reported feature of this study’s analysis. The record does not describe whether repeated observations were included in the primary calculation or how any dependence was handled.
What do planning illustrations mean?
In general, a sample-size calculation uses assumptions about the effect to detect, variability, significance level, power and design to illustrate the amount of information a future study may need. The registry record’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It distinguishes participants per arm for non-time-to-event outcomes from the total number of events for time-to-event calculations. These are planning assumptions, not observed trial results or observed power.
The registry record does not report the numerical planning outputs or the effect value used in those illustrations. The trial itself is listed as single-group, so the equal-allocation two-arm assumption describes a planning scenario rather than this study’s treatment allocation. Such illustrations cannot be used to infer the study’s actual design, justification, or ability to detect an effect.
What analysis details remain unknown?
The registry record does not report the statistical methods used to calculate the primary percentage, the agreement threshold, a confidence interval method, hypothesis tests, covariate adjustments, or a prespecified analysis plan. It also does not report whether there were interim analyses or how multiplicity was handled across outcomes. These items are not reported in the registry record; their absence should not be filled in by assuming common practices. With the methods and results both incomplete, the endpoint’s estimate cannot be independently reproduced or its statistical uncertainty evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists six outcome measures in total: the primary dose-indicator agreement measure and secondary outcomes involving other count comparisons, undercounting and correct advances. It lists zero analyses. Although the outcomes indicate that multiple measurement questions were of interest, the record does not report a statistical plan describing which outcomes were confirmatory, how they were prioritized, or whether any adjustment for multiple testing was made. These details are not reported in the registry record.
In general, testing or estimating many outcomes can create interpretive challenges. When multiple hypothesis tests are conducted, the chance of at least one apparently notable result can increase unless the analysis accounts for multiplicity. This general concern does not establish that a particular adjustment was required or performed in this study. No test results or multiplicity procedures are reported in the registry record, so the impact of multiple outcomes cannot be assessed.
The primary outcome names the ITT Population and uses the last available visit. The registry record does not define the analysis population, state whether all enrolled participants or devices contributed, describe exclusions, or report how missing counts were handled. It does not say whether missing observations were imputed, treated as non-agreement, or excluded from the denominator. Those procedures are not reported in the registry record.
Because the endpoint is a percentage, the denominator and missing-data rules are important to interpretation. Without them, readers cannot determine precisely which observations the reported percentage would represent, even if the numerical result were available. No observed primary result is reported in the registry record.
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 |
|---|---|---|---|
| GFF MDI (PT003) | 3 | 138 | 2.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| GFF MDI (PT003) | 10 of 138 |
Most frequent serious adverse event terms
| Event term | Organ system | GFF MDI (PT003) |
|---|---|---|
| COPD | Respiratory, thoracic and mediastinal disorders | 2 of 138 |
| Metastatic Neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 138 |
| Metastatic Pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 138 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GFF MDI (PT003) |
|---|---|---|
| COPD | Respiratory, thoracic and mediastinal disorders | 10 of 138 |
Serious events with the highest arm-level rate: copd (1.4%), metastatic neoplasm (0.7%), metastatic pain (0.7%).
The safety figures describe one listed group, GFF MDI (PT003). The registry record reports 3 participants with serious adverse events among 138 at risk, and 10 with other adverse events among 138 at risk. These are separate registry categories. The record also lists COPD at 1.4%, Metastatic Neoplasm at 0.7%, and Metastatic Pain at 0.7% among the top serious adverse event terms.
These figures should be read as descriptive safety reporting for the single study group. They do not provide a comparison with an untreated or alternative-treatment group, and they do not by themselves establish whether an event was caused by the inhaler. The record does not report event-level narratives, exposure-adjusted rates, or a comparative safety analysis. Deaths are not reported in the registry record.
The percentages attached to serious-event terms are registry-listed values and should not be interpreted as estimates of treatment-attributable risk. Serious adverse events and other adverse events are reported separately, so the categories should not be combined. The record does not provide enough detail to infer more about the timing, duration, severity distribution, or causal assessment of these events.
12. What the Result Does, and Does Not, Mean
This study addresses a measurement question: how consistently the GFF MDI dose indicator’s actuation count agrees with other counts over the canister’s use. Its primary endpoint is a percentage based on agreement between a CRF-based indicator count and a subject-reported count at the last available visit. The registry record identifies this question and names the population and timeframe, but does not report the observed percentage or its precision.
Accordingly, the record does not establish the magnitude of agreement. It cannot support a conclusion that the indicator was accurate or inaccurate, reliable or unreliable, because the relevant numerical results and analysis details are not reported. Nor does this endpoint directly answer whether the inhaler changes COPD outcomes. The study is a single-group dose-indicator study, not a randomized comparison of treatment strategies.
The additional listed outcomes could describe agreement using different count references, the frequency of a specified undercount, and correct advances within stated tolerances. Their results are not reported in the registry record. Without those values and their denominators, readers cannot compare the measurement approaches or determine how often the indicator met the described classifications.
The safety information is also descriptive for the study group. It records serious and other adverse events, along with selected serious-event terms, but does not provide a control-group comparison or establish causation. The figures should therefore be understood as reported event counts and term percentages in this study, not as comparative estimates of risk.
Overall, the registry record gives a useful description of the study’s measurement objective and endpoint definitions, but the numerical outcome results and key analysis details are not reported. The intended question is clear; the empirical answer and the precision with which it was estimated are not available in the registry record.
13. Why This Trial Matters Statistically
Device-count studies raise statistical questions that are different from those in a conventional treatment comparison. The focus is whether a measurement device records actuations consistently relative to specified reference counts. Choosing the reference, defining agreement, and determining which devices contribute to the percentage all affect what the result means. This study’s listed comparisons make those choices visible as distinct measurement questions.
The distinction between agreement and correlation is especially relevant. A measure can track another measure while still differing from it in a systematic way. Agreement therefore requires a definition of acceptable closeness, not merely evidence that two counts tend to vary together. The registry record identifies agreement as the primary construct, but does not report the operational rule or numerical result.
The study also illustrates why reporting denominators and missing-data procedures matters for percentage outcomes. Readers need to know which devices were assessed and how unavailable counts were handled to understand what share the estimate represents. The record names the ITT Population and last available visit, but does not report these details.
Finally, a single-group design can address device performance without answering a comparative treatment question. That distinction helps prevent overinterpretation of measurement endpoints as evidence about clinical benefit. Here, the registry record states an evaluation of dose-indicator accuracy, reliability and functionality; it does not report the primary numerical result or a comparative clinical outcome. The statistical value of the record is therefore primarily in clarifying the measurement question and identifying what information would be needed to judge its answer.
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 statistical interpretation is that the registry record does not report the primary outcome estimate. The percentage of devices in agreement, the number assessed, and an uncertainty interval are not available. The record also does not report numerical results for the listed secondary outcomes, despite identifying six outcome measures in total.
Important operational details are not reported in the registry record, including the rule used to define agreement, the analysis denominator, and how the count references were collected and reconciled. The record does not explain how missing observations or incomplete canister use were handled. These omissions limit assessment of reproducibility and of how representative an endpoint estimate would be.
The study is open-label and single-group, with no randomized comparator listed. This design matches a device-count evaluation but does not allow a randomized between-group treatment comparison. The record does not report a statistical analysis plan, methods for uncertainty estimation, or any multiplicity procedure. It also does not report participant characteristics beyond the stated adult COPD population and severity range.
The registry record reports safety figures for the single group, but does not provide a comparative safety analysis or enough event detail to infer causation. Finally, planning assumptions are described for a two-arm illustration, while the trial is listed as single-group. No numerical planning outputs are reported, and those assumptions should not be mistaken for the trial’s own design rationale or observed power.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Glycopyrronium and Formoterol Fumarate (GFF) Metered Dose Inhaler (MDI) Dose Indicator Study in Adults With Moderate to Very Severe COPD — NCT02268396.
- Registry record last updated 2016-12-23; status last verified 2016-10.
- Results first posted 2016-12-23.
- 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
NCT02268396 is a completed, open-label, multi-center Phase 3 study of the GFF MDI dose indicator in adults with moderate to very severe COPD. It is listed as a single-group study, with enrollment of 138 and a 4-week Treatment Period. The primary endpoint is the percentage of devices in agreement between a CRF-based dose indicator count and a subject-reported actuation count at the last available visit in the ITT Population.
The registry record lists six outcome measures and zero analyses. It describes secondary comparisons using other count references, undercounting and correct advances. It reports serious and other adverse event counts for the single group, but does not report deaths. Most importantly, the numerical primary endpoint result, its precision, and key analysis details are not reported in the registry record.