A Study to Assess the Safety and Tolerability of Once Daily Inhaled Doses of GSK573719 Made With Magnesium Stearate in Subjects With Chronic Obstructive Pulmonary Disease(COPD)for 7 Days: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Safety and Tolerability of Once Daily Inhaled Doses of GSK573719 Made With Magnesium Stearate in Subjects With Chronic Obstructive Pulmonary Disease(COPD)for 7 Days (NCT00732472), a randomized phase 2 study. The primary outcome is Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE).

2. Clinical Question

The question is about short-term safety and tolerability of this formulation, rather than whether it improves COPD symptoms or lung function. The study summary describes the magnesium stearate formulation as a way to help maintain the quality of the study medicine. It also says that safety measures included electrocardiograms, heart rate, blood pressure, safety laboratory tests, lung function, and 24-hour heart monitoring. These measures provide context for the study’s safety focus, but their results are not reported in the registry record as a single overall assessment.

The secondary outcomes concern pharmacokinetics: drug exposure and concentration measures in blood, and measures of drug or metabolite excretion in urine. They include measures on Day 1 and Day 7. The central statistical question remains how many participants experienced an on-treatment AE or SAE during the stated timeframe, and how much detail the posted results offer for interpreting that count.

3. Trial Design

This was a Phase 2, randomized, double-blind, parallel-group study with dose escalation and placebo control. Its official title describes a 2-cohort design examining safety, tolerability, and pharmacokinetics of once-daily inhaled GSK573719 formulated with magnesium stearate in COPD participants for 7 days. The record reports enrollment of 37. The study is marked completed, with a start date of 2008-10 and primary completion in 2009-08.

The study summary describes two groups of 12 people: one group was to receive 250mcg or placebo, and the other 1000mcg or placebo. It states that dosing in the higher-dose group would wait until at least 6 participants had completed dosing in the first group without significant safety concerns. This is a description of the planned dose-ascending sequence, not evidence about what safety findings occurred or how the decision was made. The registry record does not report a detailed escalation decision process.

The adverse-event listing uses four group labels: Placebo, Cohort 1 UMEC 250 µg, Cohort 2 UMEC 250 µg in Error, and Cohort 3 UMEC 1000 µg. The label identifying an erroneous 250 µg dose is important context when reading the arm-level safety counts. The registry record does not explain further how that group label relates to the two-cohort description in the study summary.

The primary endpoint timeframe runs from treatment start to study day 12, while dosing is described as lasting 7 days. Secondary outcomes include blood pharmacokinetic measures such as AUC, Cmax, and Tmax, as well as urine excretion measures and renal clearance. The exact statistical analysis plan, randomization method, allocation concealment procedures, and sample-size justification are not reported in the registry 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: Participants were assigned to one of two cohorts: UMEC 250 micrograms (μg) once daily (QD) or placebo (Cohort 1) and UMEC 1000 μg QD or placebo (Cohort 2) for 7 days. After reporting of Cohorts 1 and 2, it was found that par. in Cohort 2 received UMEC 250 μg in error. Cohort 3 was then recruited, in which par. received UMEC 1000 μg QD or placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All Subjects Population: all participants who received at least one dose of study medication

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 Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE), measured over From start of treatment to study day 12.

The primary endpoint counts participants with any on-treatment AE or any on-treatment SAE. An AE is defined in the record as an untoward medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related to that product. An on-treatment event is one that occurs between the start of investigational product and follow-up contact. An SAE is defined by outcomes such as death, a life-threatening event, hospitalization or prolonged hospitalization, disability or incapacity, or a congenital anomaly or birth defect.

This endpoint is used to describe the number of participants who experience a safety event during the specified treatment and follow-up period. Counting participants rather than event episodes answers whether a participant experienced at least one event; it does not describe how many events an affected participant had, how long events lasted, or their severity beyond the distinction between serious and other events. The listed endpoint also combines any AE with any SAE, so a participant with either type qualifies.

In general, an event-count endpoint is useful for a short safety study because it gives a direct summary of how many treated participants experienced an event. It is not, by itself, a measure of comparative treatment benefit or proof that an event was caused by the study drug. The registry record defines this outcome and its population, but a single combined arm-level result for the primary endpoint is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either had at least one qualifying on-treatment AE or SAE during the endpoint timeframe, or did not. A binary outcome is often summarized by the number of participants with an event and the number assessed in each group. The adverse-event listing gives group-specific numbers at risk and counts affected by serious and other events. It does not report a single combined arm-level result for the primary endpoint.

What does a participant count represent?

A participant count is not an event count. If one participant experiences multiple events, that participant can still count once for an outcome defined as the number with any event. The registry endpoint is phrased in terms of participants with any AE or SAE. The posted adverse-event listing separately provides the number affected by serious events and other events, but does not report the combined endpoint result or a count of all event episodes. These distinctions matter because participant-level frequency and total event burden answer different questions.

In general, binary outcomes can be described using event counts and denominators, and may be compared using measures such as a risk difference or a risk ratio. These are general methods; no such comparative estimate is reported for this primary outcome in the registry record. Nor are a confidence interval, p-value, or adjusted model reported for the primary safety endpoint. Without those details, the listed group counts should be interpreted descriptively rather than as a formal test of differences.

How should uncertainty be understood?

In general, uncertainty reflects both the observed data and the statistical model used to analyze them. For an event count, a confidence interval can communicate how imprecise an estimate may be, especially when group sizes are small. A p-value, if reported, would address compatibility with a specified null hypothesis under stated assumptions; it would not measure the size or clinical importance of a difference. Neither confidence intervals nor p-values for the primary endpoint are reported in the registry record. No new interval or test should be inferred from the posted counts.

The planning assumptions describe an 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 effect to detect is described as a fraction of the observed effect. Such planning illustrations are not observed power and are not evidence that the original study was designed with those assumptions. The sample-size justification for the trial itself is not reported in the registry record. The primary outcome is also not reduced to a single comparison for this illustration because it has several categories or time points.

What do the secondary measures add?

The secondary outcomes list mean AUC(0-2), AUC(0-8), and AUC(0-t), Cmax, Tmax, and Tlast on Day 1 and Day 7. These are pharmacokinetic measures of drug exposure and timing. Other listed measures concern amounts and fractions excreted in urine over specified intervals, renal clearance, and urine half life on Day 7. In general, such measurements describe how drug levels change over time and how the drug is handled by the body. They are distinct from the primary participant-level safety outcome. Numerical results for these secondary measures are not reported in the registry record details.

The record reports 23 outcome measures and 12 analyses. Multiple outcomes and repeated time points create opportunities for many statistical comparisons. In general, the more comparisons made, the greater the chance that some result may appear noteworthy by chance if no adjustment or prespecified hierarchy is used. The statistical plan, including any multiplicity strategy, is not reported in the registry record. It is therefore not possible to determine which outcomes were treated as confirmatory or whether the reported analyses accounted for repeated testing.

Which analysis population is described?

The primary outcome population is defined as all participants who received at least one dose of study medication. This is a treated-participant population, not necessarily the same as every participant randomized. The registry record does not report how many randomized participants did not receive treatment, nor does it describe a separate intention-to-treat analysis population. It also does not report detailed methods for handling missing outcome information, withdrawals, or incomplete follow-up. In general, missingness can affect both the number included in an analysis and the interpretation of observed event rates; the handling method should be specified to assess that possibility.

Finally, a double-blind design can reduce some sources of bias in treatment assignment and outcome assessment, but the registry description alone does not show whether blinding was maintained or how outcome assessments were conducted. The randomization procedure and allocation concealment are not reported in the registry record. These omissions limit assessment of the analysis from the posted information, without changing the descriptive meaning of the event counts that are listed.

10. Multiplicity, Missing Data and Analysis Populations

The study lists multiple outcomes, including a primary safety endpoint and numerous pharmacokinetic measures collected at more than one time point. The registry record reports 23 outcome measures and 12 analyses. When many outcomes or comparisons are examined, there is a general risk that some may appear unusual by chance. Statistical plans commonly address this through a prespecified hierarchy, adjustment for multiplicity, or clear labeling of exploratory analyses. The multiplicity strategy is not reported in the registry record, so it is not possible to determine whether or how this issue was addressed.

Missing-data methods are also not reported in the registry record. The primary population is defined as all participants who received at least one dose, but the record does not describe how participants with incomplete follow-up or missing event information were handled. It also does not report a separate intention-to-treat population or the number randomized who did not receive treatment. In general, missing outcome data can change the denominator and may affect how well observed results represent the enrolled population.

The record provides a primary endpoint definition and timeframe, but does not report the full statistical analysis plan, the handling of protocol deviations, or whether any interim analyses were conducted. These details are needed to evaluate prespecification and analysis choices. Their absence does not invalidate the posted counts, but it limits a fuller assessment of how the results were selected, analyzed, and interpreted.

11. Safety Results

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

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 serious-event figures are zero in each listed group: Placebo, Cohort 1 UMEC 250 µg, Cohort 2 UMEC 250 µg in Error, and Cohort 3 UMEC 1000 µg. The respective numbers at risk are 9, 10, 10, and 9. The registry record lists no serious-event terms. These are observed counts for this study; a zero count does not establish that serious events are impossible or that the treatment has no serious risks.

The listing separately reports other adverse events affecting 6 of 9 participants in Placebo, 2 of 10 in Cohort 1 UMEC 250 µg, 8 of 10 in Cohort 2 UMEC 250 µg in Error, and 5 of 9 in Cohort 3 UMEC 1000 µg. These figures should not be mistaken for a causal comparison. The registry record does not report confidence intervals or a formal statistical comparison for these counts, and the primary endpoint’s combined count of participants with any AE or SAE is not reported in the registry record.

These summaries describe whether participants were affected, not the number, duration, severity, or relatedness of individual non-serious events. The registry record points to a general AE module for a complete list, but a complete list of event terms is not included in the registry entries. The group label “Cohort 2 UMEC 250 µg in Error” is retained as recorded and warrants caution when interpreting that group.

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

The posted data describe a short, randomized, double-blind, placebo-controlled study of once-daily inhaled GSK573719 formulated with magnesium stearate in people with COPD. The study assessed safety and tolerability over 7 days and included pharmacokinetic outcomes. Its primary endpoint was the number of participants with any on-treatment AE or SAE through study day 12. The registry record reports zero serious events in each listed group and gives counts of participants affected by other adverse events.

These findings do not establish whether the formulation is effective for COPD, because the stated primary question concerns safety and tolerability rather than clinical benefit. They also do not establish that treatment caused or did not cause any particular event. The event definition explicitly includes occurrences whether or not considered related to the medicinal product, and the posted arm-level results do not provide a causal assessment for each event.

The results do not establish equivalence between treatment and placebo, nor do they show that a lack of observed serious events means no serious risk exists. The groups were small, the observation period was short, and the registry record does not report confidence intervals or a formal comparison for the listed event counts. In general, limited sample sizes and follow-up can leave uncertainty about less common or later events; this is a general limitation of short safety studies, not a claim that such events occurred in this trial.

The record also does not report a combined primary-endpoint count, a detailed statistical analysis plan, missing-data methods, or numerical results for the listed pharmacokinetic outcomes. Those absences limit what can be concluded about comparative precision and the full set of study outcomes. The appropriate interpretation is therefore narrow: the posted adverse-event listing records no serious events in the listed groups and reports the specified counts of other affected participants during the study’s short assessment period.

13. Why This Trial Matters Statistically

This study is statistically interesting because its main question is safety-focused and its treatment sequence is dose-ascending. The study summary describes a planned pause before dosing the higher-dose group until at least 6 participants had completed dosing in the first group without significant safety concerns. This illustrates how safety monitoring can be part of a staged study design. The registry record does not provide the detailed decision rules or the evidence used to make the escalation decision.

The endpoint also highlights the difference between a broad participant-level safety outcome and an event-by-event account. Counting participants with any AE or SAE gives a compact summary, while separate serious and other event counts provide additional descriptive information. Neither form alone captures the complete clinical character of events, and the registry record does not provide a single combined primary-endpoint result.

The small group counts make precision important. In general, descriptive differences between small groups may be unstable, and confidence intervals help show uncertainty around estimates. No such intervals or formal comparative analysis are reported for the adverse-event counts. The treatment group labelled “Cohort 2 UMEC 250 µg in Error” also makes careful attention to the recorded group labels essential; it should not be reinterpreted as a planned dose category without further documentation.

Finally, the multiple pharmacokinetic measures and time points raise a general question about multiplicity and prespecification. The registry record names these outcomes but does not report the statistical plan or multiplicity approach. The case therefore illustrates why trial interpretation depends not only on event counts, but also on outcome definitions, group labeling, uncertainty estimates, and transparent analysis methods.

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 registry record reports enrollment of 37 and describes dosing over 7 days, with the primary safety timeframe extending through study day 12. This is a short observation period, so the posted findings address only events captured within the recorded study timeframe. The record does not report longer-term safety follow-up in the listed primary endpoint.

The adverse-event listing gives small group-specific denominators and counts, but does not report confidence intervals or a formal comparison. It also does not provide a single combined result for the primary endpoint of any on-treatment AE or SAE. The listed event counts therefore cannot support a precise estimate of between-group differences from the registry record alone.

The adverse-event groups include a label identifying “Cohort 2 UMEC 250 µg in Error.” The registry record does not explain this label beyond its wording, limiting interpretation of that group in relation to the planned dose-ascending design. The group labels and their counts should be read as recorded rather than reconciled by assumption.

Important methodological details are not reported in the registry record, including the randomization procedure, allocation concealment, statistical analysis plan, handling of missing data, multiplicity strategy, and any interim analyses. The record also does not provide baseline participant characteristics, a complete event-term listing in the available information, or numerical secondary pharmacokinetic results. These gaps limit assessment of comparability, precision, and the full safety and pharmacokinetic profile.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Assess the Safety and Tolerability of Once Daily Inhaled Doses of GSK573719 Made With Magnesium Stearate in Subjects With Chronic Obstructive Pulmonary Disease(COPD)for 7 Days — NCT00732472.
• Registry record last updated 2016-11-23; status last verified 2016-10.
• Results first posted 2014-02-17.
• 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

NCT00732472 is a completed Phase 2 randomized, double-blind, placebo-controlled, parallel-group study of once-daily inhaled GSK573719 formulated with magnesium stearate in participants with COPD. The record reports enrollment of 37, a start date of 2008-10, and primary completion in 2009-08. The study summary describes 7 days of dosing and a dose-ascending approach.

The primary endpoint counts participants with any on-treatment AE or SAE from treatment start through study day 12. The listed serious-event count is zero in each of four adverse-event groups. Other adverse events affected 6 of 9 participants in Placebo, 2 of 10 in Cohort 1 UMEC 250 µg, 8 of 10 in Cohort 2 UMEC 250 µg in Error, and 5 of 9 in Cohort 3 UMEC 1000 µg. A combined primary-endpoint result, formal comparisons, confidence intervals, detailed analysis methods, and numerical secondary pharmacokinetic results are not reported in the registry record.