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 Pharmacokinetics and Safety of BI 1744 CL Plus Tiotropium Bromide in Chronic Obstructive Pulmonary Disease (COPD) (NCT02231177), a randomized phase 1 study. The primary outcome is AUC(0-1h,ss) of Olodaterol.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02231177 |
| Phase | Phase 1 |
| Condition | Pulmonary Disease, Chronic Obstructive |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 47 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
Participants had chronic obstructive pulmonary disease. The trial enrolled 47 participants; the primary endpoint population was narrower, comprising treated participants with evaluable endpoint data who met the registry’s stated pharmacokinetic-set criteria.
Intervention
The combination was 10 μg BI 1744 CL plus 5 μg tiotropium bromide, given once daily through the Respimat inhaler during 21-day treatment periods. The registry describes the endpoint analyte as olodaterol.
Comparator
The primary posted comparison is the combination against 10 μg BI 1744 CL alone, identified in the results as olodaterol 10 µg. The study also included tiotropium 5 µg as a single-agent treatment.
Primary question
At steady state, how did plasma olodaterol exposure over the first hour after dosing compare between the fixed-dose combination and olodaterol alone? The primary measure was AUC(0-1h,ss), with adjusted geometric means and an adjusted geometric mean ratio reported from an ANOVA model.
This is a pharmacokinetic question: it concerns the amount of drug measured in plasma over a specified interval, rather than a clinical outcome such as symptoms or disease progression. The registry also describes secondary objectives concerning safety and tolerability, including adverse events, electrocardiogram recordings and pulmonary function testing. Those objectives are distinct from the primary exposure comparison.
3. Trial Design
The registry describes a randomized, double-blind, three-way crossover study in participants with chronic obstructive pulmonary disease. The planned treatments were BI 1744 CL plus tiotropium as a fixed-dose combination, BI 1744 CL alone and tiotropium alone. Each treatment was administered once daily via the Respimat inhaler for 21 days. The primary endpoint was assessed at steady state on Day 21 of the actual treatment period.
In a crossover design, participants receive more than one treatment in separate treatment periods, so within-participant comparisons can contribute to the analysis. This differs from a parallel-group design, in which participants remain in one assigned treatment group. Randomization and double blinding are recorded, but the sequence allocation details, any washout arrangements and how treatment-period or sequence effects were handled are not reported in the registry record. The arm descriptions are blank, so they do not add detail about treatment sequences.
The registry records enrollment of 47 participants and identifies the study as Phase 1. The primary endpoint analysis includes evaluable pharmacokinetic data for 39 participants in the combination treatment group and 37 in the olodaterol treatment group. These endpoint counts are not the same as the overall enrollment figure; the registry’s endpoint population definition restricts analysis to participants with evaluable data and no important protocol violations under its stated criteria.
The results identify a primary comparison between combination treatment and olodaterol alone. Although tiotropium alone was also a treatment, the primary result reported is not a three-treatment comparison. How the randomized treatment sequences were distributed, and whether all participants completed all treatment periods, 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: A randomised, double-blind, 3-way crossover study, each patient received each of the three treatments for 21 days according to randomisation.
Treatment Period 1 (21 Days)
| Stage | Tio+Olo 5/10 μg, Olo 10 μg, Tio 5 μg | Tio+Olo 5/10 μg, Tio 5 μg, Olo 10 μg | Olo 10 μg, Tio+Olo 5/10 μg, Tio 5 μg | Olo 10 μg, Tio 5 μg, Tio+Olo 5/10 μg | Tio 5 μg, Tio+Olo 5/10 μg, Olo 10 μg | Tio 5 μg, Olo 10 μg, Tio+Olo 5/10 μg |
|---|---|---|---|---|---|---|
| STARTED | 8 | 7 | 8 | 7 | 8 | 9 |
| COMPLETED | 8 | 7 | 8 | 7 | 8 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Treatment Period 2 (21 Days)
| Stage | Tio+Olo 5/10 μg, Olo 10 μg, Tio 5 μg | Tio+Olo 5/10 μg, Tio 5 μg, Olo 10 μg | Olo 10 μg, Tio+Olo 5/10 μg, Tio 5 μg | Olo 10 μg, Tio 5 μg, Tio+Olo 5/10 μg | Tio 5 μg, Tio+Olo 5/10 μg, Olo 10 μg | Tio 5 μg, Olo 10 μg, Tio+Olo 5/10 μg |
|---|---|---|---|---|---|---|
| STARTED | 8 | 7 | 8 | 7 | 8 | 9 |
| COMPLETED | 8 | 7 | 8 | 7 | 8 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Treatment Period 3 (21 Days)
| Stage | Tio+Olo 5/10 μg, Olo 10 μg, Tio 5 μg | Tio+Olo 5/10 μg, Tio 5 μg, Olo 10 μg | Olo 10 μg, Tio+Olo 5/10 μg, Tio 5 μg | Olo 10 μg, Tio 5 μg, Tio+Olo 5/10 μg | Tio 5 μg, Tio+Olo 5/10 μg, Olo 10 μg | Tio 5 μg, Olo 10 μg, Tio+Olo 5/10 μg |
|---|---|---|---|---|---|---|
| STARTED | 8 | 7 | 8 | 7 | 8 | 9 |
| COMPLETED | 8 | 7 | 8 | 7 | 8 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) set which included all patients in the treated set who provided at least one of the PK parameters in at least one treatment period and completed the trial without any important protocol violations, it is however restricted to patients with evaluable data for this endpoint.
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: Treated Set. All randomised patients who received at least one dose of trial medication were included in the treated set.
| Characteristic | Unit | All Subjects |
|---|---|---|
| Participants analysed | 47 | |
| Age, Continuous | years | 59.8 (SD 7.4) |
| Sex: Female, Male: Female | Participants | 22 |
| Sex: Female, Male: Male | Participants | 25 |
6. Primary Endpoint
The registry lists the primary outcome as AUC(0-1h,ss) of Olodaterol, measured over Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | pg*h/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint, AUC(0-1h,ss) of olodaterol, measures the area under the plasma concentration-time curve from dosing to one hour at steady state. Its unit is pg*h/mL. AUC represents drug exposure accumulated over the specified interval; it is not a direct measure of symptom change or another clinical outcome.
The registry states that plasma olodaterol concentrations were not expected to be quantifiable throughout the full dosing interval in all participants. It therefore selected the interval ending at the time point where at least 2/3 of participants had quantifiable concentrations, defining the primary interval as zero to one hour. This rationale links the endpoint window to the expected availability of measurable concentration data, rather than to a clinical threshold.
The reported treatment summaries are adjusted geometric means, and dispersion is expressed as geometric coefficient of variation. The registry identifies an ANOVA model as the source of the adjusted values. Geometric summaries are used for data analyzed on a logarithmic scale; in general, they describe the central level on the original scale after analysis on that transformed scale. The ratio of adjusted geometric means compares the modeled exposure between the combination and olodaterol-alone treatments.
The endpoint assessment was scheduled around drug administration on Day 21, with concentration sampling extending through 24:00 hours. The primary endpoint uses only the first hour of that sampling schedule. The registry’s stated endpoint population is limited to participants with evaluable data for this measure.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary result compares adjusted geometric mean olodaterol exposure over the first hour at steady state for the fixed-dose combination and olodaterol alone. The adjusted geometric means are 4.67 pg*h/mL for Tiotropium+Olodaterol 5/10 μg and 4.15 pg*h/mL for Olodaterol 10 µg. The reported adjusted geometric mean ratio is 1.12, with a 90% confidence interval from 0.99 to 1.27. The geometric coefficient of variation is 32.15 for each treatment summary.
The ratio expresses the modeled comparison on a relative scale: a value of 1 would correspond to equal adjusted geometric means. The reported interval includes 1. In general, a confidence interval describes a range of values compatible with the data and analysis under the method’s assumptions; its width conveys uncertainty. This interval extends on both sides of 1, so the reported estimate does not rule out equality at the confidence level used. The registry does not report a p-value for this analysis.
The result is specific to the olodaterol plasma-exposure endpoint, its first-hour window and the stated endpoint population. It does not establish whether the treatments differ on a clinical outcome, and it does not summarize the comparison involving tiotropium alone. The two treatment summaries use different endpoint-specific participant counts: 39 for the combination and 37 for olodaterol alone. The enrollment figure of 47 should therefore not be read as the number contributing data to each primary endpoint summary.
The geometric coefficient of variation describes variability on the geometric scale, not the uncertainty of the ratio estimate. The confidence interval is the relevant reported measure for uncertainty in the treatment comparison. The registry does not report additional detail about model assumptions, treatment-period effects or the handling of any missing concentration measurements, so the precision and interpretation cannot be evaluated beyond the posted model result and endpoint definition.
These data characterize pharmacokinetic exposure in this study. They should not be translated into a claim about clinical benefit, harm or equivalence. The confidence interval is compatible with a range of relative exposure values, and its interpretation is tied to the model and the analyzed participants. Other outcomes, including the registry’s secondary safety and pharmacokinetic measures, address different questions and should not be treated as interchangeable with the primary endpoint.
9. Statistical Methods Explained
The registry reports an ANOVA model for the primary endpoint and describes its displayed treatment values as adjusted geometric means with intra-subject variability. In a crossover study, measurements from the same participant under different treatments are related rather than independent. In general, an analysis that accounts for this structure can use within-participant information while estimating treatment differences. The exact model terms and implementation are not reported in the registry record, so the model’s detailed handling of participant, period, sequence or carryover effects cannot be reconstructed from the description.
What does the geometric mean ratio express?
The endpoint values are analyzed and summarized on a geometric scale. In general, a geometric mean is suited to positive measurements that are analyzed after logarithmic transformation. A ratio of geometric means expresses the relative level of one treatment compared with another. A ratio of 1 corresponds to equal values; values on either side indicate the direction of the modeled comparison. The posted adjusted ratio is 1.12 for combination treatment relative to olodaterol alone.
The ratio is a model-based comparison, not a raw difference in concentration or exposure. The reported adjusted geometric means are 4.67 pg*h/mL and 4.15 pg*h/mL, respectively. No further arithmetic contrast is needed to interpret the reported ratio. Because the analysis is described as adjusted, it should not be assumed to be identical to a simple comparison calculated directly from the displayed summaries.
How should the confidence interval be read?
The reported 90% confidence interval for the ratio is 0.99 to 1.27. In general, a confidence interval conveys uncertainty around an estimate, conditional on the data and analysis method. A narrower interval indicates greater precision than a wider interval on the same scale. The interval includes 1, the value corresponding to equal adjusted geometric means. Thus the interval does not exclude equality at its stated confidence level. It also includes values above 1, indicating that the reported data and model are compatible with a range of relative exposure estimates.
The interval is not a range that contains a fixed proportion of individual participants’ exposure values. It concerns the estimated treatment ratio. It also does not account for sources of uncertainty that the registry does not describe, such as model misspecification or the consequences of missing endpoint data.
What does variability mean in this result?
The geometric coefficient of variation is reported as 32.15 for both treatment summaries. In general, a coefficient of variation expresses variability relative to a mean, and its geometric form is used with data summarized on a geometric scale. It is not the confidence interval for the treatment comparison and does not indicate the precision of the ratio by itself. The ratio’s confidence interval is the posted summary of uncertainty for the modeled comparison.
Over-dispersion is a general concern when observed variability is greater than an analysis assumes. If variability is underestimated, standard errors and confidence intervals can be too small; if it is modeled appropriately, uncertainty estimates better reflect the data. The registry does not report a separate over-dispersion assessment or enough model detail to assess this issue for the primary analysis. The coefficient of variation alone does not establish whether over-dispersion was present.
What is the role of the endpoint population?
The endpoint definition identifies a pharmacokinetic set: treated participants who provided at least one pharmacokinetic parameter in at least one treatment period and completed the trial without important protocol violations, further restricted to those with evaluable data for this endpoint. This is an endpoint-specific analysis population, not automatically the same as all enrolled participants. The primary summaries list 39 participants for the combination and 37 for olodaterol alone, while enrollment was 47.
In general, excluding participants without evaluable measurements can affect interpretation if the reasons for missing data are related to treatment or measured exposure. The registry does not report a participant flow explaining the difference between enrollment and endpoint counts, the reasons for unavailable data, or a sensitivity analysis for missing observations. Those omissions limit assessment of how representative the endpoint population is of all enrolled participants.
What do the planning illustrations mean?
Sample-size illustrations use the observed effect as a planning reference, with two-sided significance level 0.05, equal allocation between two arms and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. In general, such calculations illustrate how assumptions about the effect size and design relate to the number of participants per arm needed for a chosen power target. They are planning illustrations, not observed power and not evidence that the original trial was designed to meet those assumptions.
The registry record does not report the original sample-size justification or whether the trial’s design used these assumptions. It also does not report a protocol statistical analysis plan, interim analyses or the intended approach to multiplicity. Consequently, the illustrations cannot be treated as the original design rationale or as a substitute for the reported ANOVA analysis.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANOVA | Geometric Mean Ratio 1.12 | 0.99 to 1.27 | not reported |
The registry reports the sponsor’s primary comparison as an ANOVA-based adjusted geometric mean ratio of 1.12, with a 90% confidence interval from 0.99 to 1.27. The adjusted geometric means are 4.67 pg*h/mL for the combination and 4.15 pg*h/mL for olodaterol alone. These are the model-based results identified in the registry, and they provide the principal reported estimate for the primary endpoint.
No discrepancy is flagged between the sponsor’s analysis and any simple recalculation. A simple unadjusted recalculation, where available, is not the same estimand as an adjusted crossover-model result: it may not account for the same within-participant structure or model terms. In general, differences between adjusted and unadjusted results can arise because they use different analytical approaches, even when based on the same study data. No separate recalculated estimate or interval is reported in the registry record.
The registry does not report a p-value for the primary analysis. The confidence interval, rather than an unreported significance test, is the available uncertainty summary. The sponsor’s model result should be interpreted within the limits of the endpoint population and the model details documented in the record.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary endpoint, AUC(0-1h,ss) of olodaterol, and also records 23 outcome measures, 20 posted secondary outcomes and 10 analyses. The secondary measures include pharmacokinetic endpoints for olodaterol and tiotropium. These outcomes address multiple questions, but a list of outcomes and analyses does not by itself establish how the study controlled the chance of false-positive findings across comparisons.
The approach to multiplicity is not reported in the registry record. In general, when several endpoints or treatment comparisons are tested, multiplicity procedures may be used to manage the interpretation of multiple statistical tests. Without a stated procedure or analysis plan, the reported confidence interval for the primary endpoint should be read as the interval for that comparison, not as evidence that all secondary analyses were adjusted in a particular way. The record does not describe a hierarchy of hypotheses or identify which secondary findings, if any, were designated confirmatory.
The endpoint population is restricted to participants with evaluable primary endpoint data and the stated pharmacokinetic-set criteria. The record gives 39 participants for the combination summary and 37 for olodaterol alone, compared with enrollment of 47. It does not explain the participant-level reasons for those endpoint counts, whether data were missing in particular treatment periods, or whether missingness differed by treatment.
The handling of missing concentration values, protocol deviations and incomplete treatment periods is not reported in the registry record beyond the endpoint population definition. No imputation method or missing-data sensitivity analysis is described. These omissions matter because endpoint-specific exclusions can affect both the analyzed population and the uncertainty of the estimate. The registry also does not report interim analyses, the original statistical analysis plan or the sample-size justification. No assumptions about those procedures should be inferred from the posted results.
12. 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 |
|---|---|---|---|
| Tiotropium+Olodaterol 5/10 μg | 0 | 47 | 0.0% |
| Olodaterol 10 µg | 0 | 47 | 0.0% |
| Tiotropium 5 µg | 0 | 47 | 0.0% |
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 |
|---|---|
| Tiotropium+Olodaterol 5/10 μg | 6 of 47 |
| Olodaterol 10 µg | 10 of 47 |
| Tiotropium 5 µg | 9 of 47 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tiotropium+Olodaterol 5/10 μg | Olodaterol 10 µg | Tiotropium 5 µg |
|---|---|---|---|---|
| Headache | Nervous system disorders | 3 of 47 | 3 of 47 | 5 of 47 |
| Nasopharyngitis | Infections and infestations | 2 of 47 | 4 of 47 | 3 of 47 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 47 | 5 of 47 | 1 of 47 |
The serious adverse event figures list 47 participants at risk in each of the three treatment groups: Tiotropium+Olodaterol 5/10 μg, Olodaterol 10 µg and Tiotropium 5 µg. The registry records 0 serious adverse events in each group. These are counts over the safety reporting shown, not estimates that serious events are impossible or absent in other settings.
The registry’s death counts are not reported in the registry record. The record separately lists 6, 10 and 9 other adverse events in the respective treatment groups; those counts are distinct from the serious adverse event counts and should not be combined with them. The registry does not provide further detail in the serious-event list because no serious-event terms are listed.
In general, safety counts describe what was observed among participants included in the stated risk group during the recorded study periods. They do not by themselves establish comparative safety, especially in a crossover study where participants may receive more than one treatment. The record does not explain how adverse events were attributed across treatment periods or provide a detailed comparative safety model. These figures should therefore be read descriptively and alongside the study’s duration and population, not as a definitive assessment of uncommon or longer-term events.
13. What the Result Does, and Does Not, Mean
The primary result describes systemic olodaterol exposure over the first hour at steady state for the combination treatment compared with olodaterol alone. The posted adjusted geometric mean ratio is 1.12, with a 90% confidence interval from 0.99 to 1.27. The interval includes 1, so the reported estimate does not exclude equal adjusted geometric means at the stated confidence level. The registry provides no p-value for this comparison.
This is a pharmacokinetic result, not a direct measure of symptom relief, disease control, quality of life or long-term clinical outcomes. It concerns one analyte, one interval and the endpoint-specific analysis population. It does not answer whether the fixed-dose combination changes outcomes important to patients, and it does not provide a primary comparison against tiotropium alone.
The study included 47 participants, but the primary endpoint summaries list 39 participants for the combination treatment and 37 for olodaterol alone. The record’s population definition and the absence of a detailed account of missing endpoint data limit conclusions about how the analyzed participants relate to everyone enrolled. The listed serious adverse event counts are zero in each treatment group, but the registry does not report death counts and the study is not described as a long-term safety assessment.
The result does not establish equivalence: no equivalence margin is reported in the registry record, and the confidence interval alone is not an equivalence test. Nor does it establish a clinically important difference. Such interpretations would require clinical context and prespecified criteria that are not reported in the registry record. The appropriate reading is narrower: the posted model estimates the relative first-hour olodaterol exposure under the studied conditions, with the stated interval expressing uncertainty around that estimate.
14. Why This Trial Matters Statistically
This trial illustrates a distinction between a pharmacokinetic comparison and a clinical-outcome comparison. AUC(0-1h,ss) summarizes measured plasma exposure during a defined interval. Its interpretation depends on the sampling schedule, the selected endpoint window and the availability of quantifiable concentrations. The registry explains that the one-hour window was selected because concentrations were not expected to be quantifiable throughout the full dosing interval for all participants.
The crossover structure also matters statistically. Because participants receive treatments in separate periods, within-participant information can contribute to comparing treatments. That design feature can be useful for pharmacokinetic questions, but it also makes the analysis dependent on how the model handles repeated measurements and treatment periods. The registry identifies an ANOVA model but does not report the model terms or treatment-sequence details, leaving important aspects of the analysis undocumented.
The result demonstrates why an estimate should be read together with its confidence interval and analysis population. The ratio is 1.12 and the 90% confidence interval is 0.99 to 1.27; the interval includes the value corresponding to equal adjusted geometric means. The endpoint summaries also use fewer participants than the total enrollment. Those details are central to understanding both the direction and the precision of the posted comparison.
Finally, the record distinguishes the primary pharmacokinetic question from a broader set of secondary outcomes and safety objectives. Without a reported multiplicity approach or a full statistical analysis plan, secondary analyses require particular care in interpretation. This study is therefore a useful example of how design, endpoint definition, analysis population and reporting detail shape what a clinical trial result can support.
15. 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 provides limited detail about the crossover implementation. It does not report the treatment sequence allocation, any washout period, the number of participants completing each period or the handling of potential period and carryover effects. Although the study is identified as randomized, double-blind and three-way crossover, those labels do not fully specify the design or its analysis.
The primary endpoint result is based on an endpoint-specific population, with 39 participants listed for the combination and 37 for olodaterol alone, while enrollment was 47. The record does not describe why endpoint data were unavailable or identify whether exclusions resulted from missing samples, protocol violations or other reasons. It also does not report a missing-data method or sensitivity analysis. This makes it difficult to assess the potential effect of exclusions on the comparison.
The statistical reporting identifies ANOVA and adjusted geometric means, but the model specification is not reported in the registry record. The handling of participant, treatment-period and sequence effects is therefore unclear. The record also does not report the original sample-size justification, the planned multiplicity strategy or whether interim analyses occurred. The sample-size illustrations associated with the posted analysis are planning illustrations, not documentation of the trial’s original design.
The primary outcome is a pharmacokinetic measure over the first hour, rather than a clinical outcome. The registry’s safety information includes serious adverse event counts, but death counts are not reported in the registry record, and the record does not provide a detailed analysis of safety across treatment periods. The study’s phase and enrollment do not, by themselves, resolve the uncertainty about the frequency of uncommon or longer-term events. These reporting limits constrain interpretation to the specific exposure comparison and observations recorded.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Pharmacokinetics and Safety of BI 1744 CL Plus Tiotropium Bromide in Chronic Obstructive Pulmonary Disease (COPD) — NCT02231177.
- Registry record last updated 2016-01-07; status last verified 2015-12.
- Results first posted 2016-01-07.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry describes a completed Phase 1 randomized, double-blind, three-way crossover study in chronic obstructive pulmonary disease, with enrollment of 47 participants. Treatments were BI 1744 CL plus tiotropium, BI 1744 CL alone and tiotropium alone, given once daily via the Respimat inhaler during 21-day treatment periods.
The primary endpoint was olodaterol AUC(0-1h,ss), assessed at steady state. The posted adjusted geometric means were 4.67 pg*h/mL for Tiotropium+Olodaterol 5/10 μg and 4.15 pg*h/mL for Olodaterol 10 µg. The adjusted geometric mean ratio was 1.12, with a 90% confidence interval from 0.99 to 1.27. The endpoint summaries list 39 and 37 participants, respectively.
The record lists 0 serious adverse events among 47 participants at risk in each of the three treatment groups. Death counts are not reported in the registry record. Details about the full statistical analysis plan, multiplicity, missing-data handling and treatment-sequence procedures are also not reported in the registry record.