A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood (NCT05934942), a na phase 1 study. The primary outcome is Area Under the Concentration-time Curve of Ethinylestradiol and Drospirenone in Plasma at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss).

2. Clinical Question

The clinical question is therefore a planned interaction question, not a result established by the posted data. The study aimed to measure the amount of each contraceptive component in plasma under the reference and test treatment conditions. Those conditions were not reached. The record describes Yasmin® use during the run-in, but that exposure alone cannot establish how either component’s concentration would compare when BI 1358894 is taken with Yasmin®. The distinction matters: a study can be designed to address a pharmacokinetic question yet produce no observations that answer it if it stops before the relevant measurements. The record gives no estimate of the size or direction of a possible change and no evidence from which to quantify its precision.

3. Trial Design

This was a Phase I, open-label, fixed-sequence, two-period, single-group trial sponsored by Boehringer Ingelheim. The registry record lists enrollment of 29 and describes the intended participants as healthy female subjects. The study started on 2023-09-08, had a primary completion date of 2024-02-08, and is listed as terminated. The record states that it was prematurely discontinued as per protocol after the run-in period.

During the run-in period, participants were treated with 1 daily tablet of Yasmin® from Day-56 to Day-8. The intended sequence then involved a reference treatment period with Yasmin® and a test treatment period with BI 1358894 and Yasmin®. However, the registry record explicitly says that none of the participants received the intended treatments because the study was discontinued after the run-in. The intended period-specific pharmacokinetic sampling therefore did not yield measurements.

Open-label means that masking was not used; the registry lists masking as NONE. Fixed-sequence describes the intended order of treatments rather than random assignment to competing sequences. The record lists allocation as NA and the model as SINGLE GROUP, so the design should not be described as a randomized comparison between independent groups. Although the planned treatment conditions could have permitted within-participant pharmacokinetic comparison if completed, that comparison is not available because the relevant treatments and measurements did not occur.

The primary endpoint was planned as the area under the concentration-time curve for ethinylestradiol and drospirenone at steady state over the uniform dosing interval. The registry record specifies a planned sampling schedule in period 1 and period 2, but the endpoint description also states that no pharmacokinetic parameter values were collected. The pharmacokinetic analysis set defined in the protocol was therefore not applicable. The record does not report a reason for discontinuation beyond stating that the study was discontinued as per protocol after the run-in period. Further operational details, including any additional decision-making process, 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: 29 female participants of child-bearing potential who met all inclusion and no exclusion criteria entered the study, 28 were treated with Yasmin® , 1 was not treated, and 1 withdrew. 27 participants completed the run-in period. No female participant received an investigational medicinal treatment in Period 1 (Yasmin® alone) or Period 2 (Yasmin® and BI 1358894). The study was prematurely discontinued as per protocol in the run-in period.

Run-in Period

Reasons for not completing this period:

Period 1 - Reference Treatment

Period 2 - Test Treatment

Analysis population for the primary outcome, as defined in the registry: The study was prematurely discontinued as per protocol after run-in period. No pharmacokinetic (PK) parameter values were collected. Therefore, the PK parameter analysis set as defined in the protocol was not applicable.

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 subjects who were entered to the trial and received Yasmin® during the run-in period.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Concentration-time Curve of Ethinylestradiol and Drospirenone in Plasma at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss), measured over Planned: pre-dose within 10 minutes before 1st drug administration, and then in period 1 and period 2 post-dose : 480:30, 481:00, 481:30, 482:00, 482:30, 483:00, 483:30, 484:00, 485:00, 486:00, 488:00, 490:00, 492:00, 504:00 hours (h).

The primary endpoint was the area under the concentration-time curve of ethinylestradiol and drospirenone in plasma at steady state over the uniform dosing interval. In general, an area under a concentration-time curve represents drug exposure over a specified period: it combines concentration measurements across time rather than describing a single blood sample. Steady-state exposure refers to the pattern expected after repeated dosing has reached a stable dosing cycle. These are general pharmacokinetic concepts, not results from this trial.

For the planned question, the endpoint was intended to describe and compare exposure to each component of Yasmin® under the reference treatment and the test treatment that combined Yasmin® with BI 1358894. Measuring exposure can help characterize whether co-administration is associated with a change in the concentration-time profile. The endpoint alone would not establish a clinical consequence; interpretation would depend on the observed values, their uncertainty, and relevant clinical context.

No endpoint values were collected. The registry record says the study ended after the run-in and that the protocol-defined pharmacokinetic analysis set was not applicable. As a result, there is no observed area-under-the-curve estimate, comparison, or measure of precision to interpret. The listed sampling times describe the intended plan, not completed measurements.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a Phase I pharmacokinetic study with an open-label, fixed-sequence, two-period plan. The actual results must be interpreted in light of the fact that the intended treatment periods did not occur. General statistical explanations below describe what the planned measures and design would ordinarily mean; they do not imply that the corresponding analyses were carried out in this trial.

What does the primary pharmacokinetic measure represent?

Area under the concentration-time curve is a summary of exposure over a defined interval. Rather than relying on a concentration at just one sampling time, it uses concentration measurements across the interval to characterize cumulative exposure. The record specifies measurement in plasma and a steady-state dosing interval for ethinylestradiol and drospirenone. Steady-state assessments are generally used when repeated dosing has produced a stable pattern across dosing intervals. These descriptions explain the planned endpoint, not any observed result: the registry states that no pharmacokinetic parameter values were collected.

The planned sampling schedule included measurements before administration and at specified times in period 1 and period 2. A schedule identifies when samples are intended to be taken; it does not demonstrate that samples were collected or that an endpoint could be calculated. Here, the registry explicitly says that the study stopped after the run-in, before the intended treatments, and that the protocol-defined pharmacokinetic analysis set was not applicable. No exposure summaries can therefore be reconstructed from the schedule alone.

How would a fixed-sequence crossover comparison work in general?

In a crossover design, each participant can receive more than one treatment condition, allowing comparison within the same participant. This can account for stable differences between participants when estimating a treatment contrast. A fixed sequence assigns the treatment order rather than randomly assigning participants to alternate sequences. General crossover analyses may need to consider period, sequence, and carryover effects, depending on the protocol and design. The registry record does not report the statistical model, any carryover assessment, or other analysis details, so no particular method should be attributed to this study.

Most importantly, within-participant comparison requires relevant observations under the different conditions. The intended reference and test periods were not completed, and no pharmacokinetic values were collected. The theoretical advantages of a crossover design therefore do not create an estimate in the absence of measurements. The planned design cannot be treated as if the crossover comparison had occurred.

What can uncertainty measures tell a reader?

In general, an estimate summarizes the observed data, while a confidence interval describes statistical uncertainty around that estimate under the assumptions of the analysis. A narrower interval generally indicates greater precision, and a wider interval indicates less precision. Neither the estimate nor its interval is available for the primary pharmacokinetic endpoint in this record. There is no basis for interpreting precision, compatibility with a range of effects, or statistical significance for the intended comparison.

A p-value is a measure calculated under a specified statistical model and null hypothesis; it is not a measure of the probability that a treatment works. No pharmacokinetic analysis was performed, and the registry lists no analyses. Accordingly, there is no p-value to interpret for the planned treatment comparison. An absent p-value is not a result showing no difference; it reflects that the analysis and its underlying endpoint observations are unavailable.

Why does over-dispersion matter in general?

Over-dispersion occurs when outcome variability is greater than a statistical model expects. If it is ignored, uncertainty estimates can be too small, making results appear more precise than warranted. This issue commonly arises in count outcomes, where a model may assume a particular relationship between the average count and its variability. It is a general consideration, not a reported feature of this trial. The record does not describe an analysis of event counts or any model that would permit assessment of over-dispersion.

For the safety counts, the registry gives descriptive participant counts rather than an inferential comparison. There is no reported model, uncertainty interval, or adjusted estimate for those figures. The counts should therefore be read as recorded frequencies within the stated run-in group, not as evidence from a comparative statistical test.

What is the role of planning calculations?

Sample-size calculations can illustrate how many participants per arm might be needed under specified assumptions about a target effect, variability, significance level, allocation, and analysis. Such calculations are planning aids. They do not establish the power actually achieved, and they do not demonstrate that an effect was observed. The registry’s assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The record does not report the trial’s own sample-size justification. More importantly, the intended pharmacokinetic contrast was not observed in this trial, so the illustration cannot supply missing endpoint evidence or be interpreted as observed power.

The registry does not report the specific statistical model planned for the pharmacokinetic endpoint, the method for estimating treatment effects, the handling of protocol deviations, or any interim analysis. Those details are not reported in the registry record. Statistical interpretation should not assume that a conventional model or a particular adjustment was used. The stated endpoint and design convey the intended question, but the record does not provide the analysis plan or results needed to assess how that question would have been estimated.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures in total and identifies minimum measured concentration of ethinylestradiol and drospirenone at steady state as a secondary outcome. It does not report the details of the remaining outcome measures beyond the primary endpoint and the listed secondary outcome. The record does not describe a multiplicity strategy, such as a hierarchy of hypotheses, adjustment of significance thresholds, or a distinction between confirmatory and exploratory analyses. Such a plan is therefore not reported in the registry record.

Multiplicity matters in general when several outcomes or comparisons are tested, because the chance of at least one apparently notable finding can increase as testing expands. This general concern does not create a multiplicity problem that can be quantified from this record: no pharmacokinetic values were collected and the registry lists no analyses. There are no endpoint estimates or test results for which an adjustment can be assessed.

The record states that the protocol-defined pharmacokinetic analysis set was not applicable because the study was discontinued after run-in and no pharmacokinetic parameter values were collected. It does not provide a fuller description of analysis populations or the participant-level membership of any population. The treatment periods intended for the pharmacokinetic comparison were not received, so the planned endpoint dataset was not formed.

Missing data procedures, including imputation, sensitivity analyses, or assumptions about why measurements might be unavailable, are not reported in the registry record. In this case, the issue is more fundamental than isolated missing samples: the intended pharmacokinetic measurements were not collected because the trial stopped before the intended treatments. No imputed or modeled endpoint result is reported. The record also does not describe an interim analysis or a statistical stopping rule.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports safety figures for the Yasmin® run-in period: 28 participants were at risk, 0 had serious adverse events, 9 had other adverse events, and 0 deaths were recorded. The figures are descriptive counts for that recorded group. They do not compare Yasmin® alone with Yasmin® plus BI 1358894, because the intended test treatment was not administered.

The serious adverse-event count should be read as the number recorded in the specified run-in group, not as proof that serious events cannot occur. The registry does not list serious adverse-event terms. It also does not provide a comparative estimate, uncertainty interval, or details that would support a broader safety conclusion. The count of other adverse events is likewise a descriptive registry figure; the record does not provide event-level descriptions in the registry record reported for this group.

The enrollment figure is 29, while the safety group lists 28 participants at risk. The registry record does not explain that difference, so the safety denominator should remain the one reported for the run-in group. These safety figures describe only the period and treatment recorded, and they cannot characterize safety during the planned co-administration period.

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

The result means that the planned pharmacokinetic assessment did not produce pharmacokinetic results. The registry record states that the study was discontinued after the run-in period, none of the participants received the intended treatments, and no pharmacokinetic parameter values were collected. The record therefore cannot quantify how BI 1358894 might affect the plasma exposure of ethinylestradiol or drospirenone when given with Yasmin®.

That absence of data is not evidence that exposure was unchanged. It is also not evidence that exposure increased or decreased. No treatment-effect estimate, confidence interval, or inferential test for the primary endpoint is reported. The direction and size of any potential pharmacokinetic difference remain unknown from this trial record. A study’s planned comparison and its observed result are distinct; the planned comparison was not completed.

The registry does record safety information from the Yasmin® run-in period. Those figures describe the recorded run-in group and do not establish what would have happened during the intended combined-treatment period. They should not be used as a comparison between treatment conditions or as a general characterization of the unadministered intervention.

The record also does not establish why the study was discontinued beyond stating that it was discontinued as per protocol after run-in. It does not report a statistical reason, a pharmacokinetic finding, or a result-based decision. The termination status alone should not be interpreted as evidence of benefit, harm, equivalence, or futility. Nor does this record answer whether the intended study design, if completed, would have detected a particular effect.

The appropriate interpretation is limited: the study was planned to examine steady-state exposure, but the relevant observations were not collected. General knowledge about pharmacokinetic endpoints or crossover designs can explain the intended approach, but it cannot fill the gap in trial-specific results. Any conclusion about the planned interaction question would require evidence beyond the measurements reported in this record.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction in clinical research: a detailed endpoint and sampling plan do not guarantee that a result will be available. The registry describes a defined pharmacokinetic question, a planned fixed sequence, and specified measurements for ethinylestradiol and drospirenone. Yet the record also states that the study ended after run-in, before the intended treatments, and that no pharmacokinetic parameter values were collected. Statistical interpretation must begin with whether the outcome data exist.

It also shows why design labels should be read alongside the actual conduct. The planned two-period sequence might ordinarily support within-participant comparison, but the intended treatment periods were not completed. The usual statistical advantages or assumptions of a crossover design cannot be invoked to imply a comparison that was never observed. Design describes how evidence was intended to be generated; it is not itself evidence.

The record is also a useful example of the limits of descriptive safety counts. Counts for the Yasmin® run-in period are reported, but they cannot answer a safety question about the planned combined treatment. A denominator and event count need to be interpreted in their actual treatment and observation context, rather than generalized to conditions that were not studied.

Finally, the trial underscores why estimates, uncertainty, and analysis plans matter. Without endpoint values, there is no effect estimate to evaluate for magnitude or precision, and no inferential result to interpret. Planning illustrations, when present, are not substitutes for observed data. The most statistically informative reading is therefore not to infer a null effect, but to recognize precisely what the record documents and what it cannot resolve.

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 principal limitation is that the study did not reach its intended pharmacokinetic assessment. The registry states that it was prematurely discontinued as per protocol after the run-in period, none of the participants received the intended treatments, and no pharmacokinetic parameter values were collected. The primary endpoint and the intended comparison therefore have no observed results in the record.

The registry does not report why the study was discontinued beyond the statement that discontinuation occurred after run-in. It does not describe the decision process, any interim findings, or whether operational considerations contributed. These details are not reported in the registry record and should not be inferred from the termination status.

The recorded safety information is confined to the Yasmin® run-in period. It does not provide safety observations for BI 1358894 in combination with Yasmin®, or a comparison with the reference treatment period. The record reports 28 participants at risk for this group, while enrollment is listed as 29; it does not explain the difference. The safety data also lack reported serious-event terms in the record details, as well as a comparative analysis.

The registry identifies the primary endpoint and one secondary outcome, but the full details of all three outcome measures are not reported. It does not report a statistical analysis model, missing-data strategy, multiplicity approach, interim analysis plan, or a trial-specific sample-size justification. These absences limit assessment of the planned inferential methods. The record also does not provide participant characteristics beyond the healthy female population description, limiting any further description of who enrolled.

Because no pharmacokinetic endpoint values exist, the study cannot establish the direction, magnitude, or precision of a possible treatment-related exposure change. These limitations concern the evidence available from this trial record; they do not imply a particular pharmacokinetic outcome.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood — NCT05934942.
• Registry record last updated 2025-02-24; status last verified 2025-02.
• Results first posted 2025-02-24.
• 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.

18. Record Summary

NCT05934942 was a Phase I, open-label, fixed-sequence, two-period, single-group study sponsored by Boehringer Ingelheim. It was intended to assess the effect of multiple doses of BI 1358894 on steady-state pharmacokinetics of ethinylestradiol and drospirenone in healthy female subjects. The record lists enrollment of 29 and describes Yasmin® use during a run-in period.

The study is listed as terminated and was discontinued after run-in. None of the intended treatments were received, no pharmacokinetic parameter values were collected, and the protocol-defined pharmacokinetic analysis set was not applicable. Thus, the primary pharmacokinetic comparison has no reported estimate or statistical analysis.

For the Yasmin® run-in group, the record lists 28 participants at risk, 0 serious adverse events, 9 other adverse events, and 0 deaths. These are descriptive run-in figures, not comparative results for the planned treatment conditions. Further details about the reason for discontinuation and several statistical procedures are not reported in the registry record.