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 Drug-drug Interaction Trial Between Rifampicin and BI 409306 in Healthy Volunteers (NCT03151499), a na phase 1 study. The primary outcome is Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03151499 |
| Phase | Phase 1 |
| Condition | Healthy |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
Healthy male subjects were enrolled. The registry record reports enrollment of 15 participants. The primary analysis population was defined as a pharmacokinetic parameter analysis set, with eligibility based on contributing at least one primary or secondary pharmacokinetic parameter that was not flagged for specified reasons.
Intervention
The test condition was BI 409306 after prior rifampicin. The registry summary describes prior 7-day intake of rifampicin tablets. The arm description identifies rifampicin pretreatment during the second period and BI 409306 administration afterward.
Comparator
The reference condition was BI 409306 without prior rifampicin. The arm description reports a single 50 mg oral dose of BI 409306 with 240 mL of water in the first period. The design was open-label and used a fixed sequence, rather than a randomized comparison.
Primary question
The primary objective was to investigate the relative bioavailability of BI 409306 after rifampicin pretreatment compared with BI 409306 without pretreatment. The primary endpoint was plasma AUC from time zero to the last quantifiable data point, AUC0-tz. The registry record does not report the endpoint estimates or a numerical comparison between conditions.
3. Trial Design
This was a phase 1, open-label, single-group, two-period fixed-sequence trial, marked completed in the registry record. Enrollment was 15, and the study population was healthy male subjects. The trial started on 2017-05-30, with primary completion on 2017-07-11. Allocation was recorded as not applicable, and masking was none.
The registered sequence began with reference treatment: a single oral dose of 50 mg BI 409306 with 240 mL of water in Period 1. The test condition followed in Period 2, after rifampicin pretreatment. The registry summary describes 7-day prior intake of rifampicin tablets; the arm description places rifampicin administration on Days -7 to -1 of Period 2. The description of the regimen is truncated in the registry record, so details beyond those statements are not available.
The study therefore addresses a pharmacokinetic comparison within a fixed sequence, rather than a randomized parallel-group contrast. Sequence matters when interpreting results: the record does not describe randomized treatment order, masking, or a separate untreated control group. It also does not report whether all enrolled participants completed both periods or how many contributed endpoint data.
The stated primary objective was to assess relative bioavailability. The secondary objective was to evaluate and compare several pharmacokinetic parameters using descriptive statistics. The registry record lists AUC0-∞ as a secondary outcome, while the full set of secondary measures and their numerical results are not reported in the record. The registered primary outcome is AUC0-tz, measured in nmol·h/L.
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: All subjects were screened for eligibility to participate in the trial. Subjects attended one specialist site which would then ensure that they (the subjects) met all inclusion/exclusion criteria. The subjects were not included into the trial if any one of the specific entry criteria were violated.
Period 1 (R)
| Stage | BI 409306 (R), Then BI 409306 After Pretreatment With Rifampicin (T) |
|---|---|
| STARTED | 15 |
| COMPLETED | 15 |
| NOT COMPLETED | 0 |
Period 2 (T)
| Stage | BI 409306 (R), Then BI 409306 After Pretreatment With Rifampicin (T) |
|---|---|
| STARTED | 15 |
| COMPLETED | 15 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) parameter analysis set (PKS): all subjects in the TS who provided at least one primary or secondary PK parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
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 (TS): This subject set includes all subjects who were entered and dispensed study medication and were documented to have taken at least one dose of investigational treatment.
| Characteristic | Unit | BI 409306 (R), Then BI 409306 After Pretreatment With Rifampicin (T) |
|---|---|---|
| Participants analysed | 15 | |
| Age, Continuous | years | 38.7 (SD 9.6) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 15 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 15 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz), measured over Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration..
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | nanomole*hour/liter (nmol·h/L) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the area under the plasma concentration-time curve for BI 409306 from time zero to the last quantifiable data point, abbreviated AUC0-tz. It is expressed in nanomole*hour/liter (nmol·h/L). The registry describes the reported statistic as a least-squares mean with standard error. Numerical estimates are not reported in the registry record.
In general, an area under a concentration-time curve summarizes measured drug concentration over time. It is used in pharmacokinetic studies as a measure of systemic exposure across the sampled interval. The “last quantifiable data point” boundary means this endpoint ends at the final sample for which the concentration can be quantified; it is distinct from AUC0-∞, which is listed as a secondary outcome and refers to an interval extrapolated to infinity.
For this trial, blood sampling was scheduled within 3 hours (h) before dosing and at 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, and 24h after administration. In general, the amount and timing of concentration measurements inform how well the observed exposure curve is characterized. The registry record does not report participant-level concentration profiles or endpoint estimates, so the exposure pattern and its precision cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The trial’s primary question concerned the relative bioavailability of BI 409306 after rifampicin pretreatment compared with BI 409306 without pretreatment. Its primary endpoint was AUC0-tz, a continuous pharmacokinetic measure. However, the registry record does not report the least-squares mean estimates, standard errors, or a numerical contrast between the conditions. It therefore does not show the direction or magnitude of the observed difference, nor the precision of any estimated comparison.
The record identifies 15 participants as enrolled, but does not state how many contributed to the primary endpoint analysis. The analysis population definition indicates that eligible subjects had to contribute at least one primary or secondary pharmacokinetic parameter that was not flagged for exclusion because of a relevant protocol violation or pharmacokinetic non-evaluability. The number meeting this definition is not reported in the registry record.
In general, an estimate describes the value calculated from the observed data, while a standard error describes the estimated uncertainty of that estimate. A confidence interval would provide a range of values compatible with the data under the analysis assumptions. Neither confidence limits nor a p-value for the primary comparison are reported in the registry record. Without an estimate and an uncertainty measure, the posted results do not permit assessment of how precisely the trial characterized the pharmacokinetic comparison.
The fixed sequence is important context. Participants received the reference condition first and the rifampicin-pretreated condition second, rather than being assigned at random to different treatment orders. A contrast across periods can therefore be affected by period or sequence conditions as well as the treatment condition. The registry record does not describe an adjustment for such effects or provide enough analysis detail to determine how the comparison was estimated. This does not establish that any particular bias occurred; it identifies a design feature relevant to interpreting a reported contrast, if one were available.
The posted results should not be read as evidence for a particular direction or size of effect. The objective and endpoint are documented, but the primary numerical results are not reported in the registry record. The same limitation applies to the listed secondary pharmacokinetic outcome, AUC0-∞: its title is present, but its estimates are not. The registry record also does not report a statistical conclusion that would resolve the primary question.
The sample-size planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. These are planning assumptions, not a description of this fixed-sequence trial’s allocation. Such illustrations are not observed power and do not replace the missing endpoint estimates. Because the observed effect is not reported in the registry record, the planning rows cannot be interpreted as evidence about the trial’s actual result.
9. Statistical Methods Explained
What does the primary measure represent?
The primary outcome is a continuous pharmacokinetic measure: AUC0-tz for BI 409306 in plasma. In general, AUC summarizes concentration over a specified time interval and is used to characterize drug exposure. AUC0-tz ends at the last quantifiable concentration, whereas the secondary outcome AUC0-∞ extends the interval by extrapolation. They are related measures, but they are not interchangeable endpoints. The registry record does not report values for either outcome.
What does the reported statistic mean?
The primary outcome is described as a least-squares mean, with standard error as its dispersion measure. In general, a least-squares mean is an estimate derived from a statistical model. Its interpretation depends on the model, including the terms and assumptions used. The model specification is not reported in the registry record, so it is not possible to say which adjustments were made or how the estimate was constructed.
In general, a standard error describes uncertainty in an estimated mean; it is not the same as the spread of individual participant values. A standard deviation describes participant-level variability, while a standard error concerns precision of an estimate. A confidence interval combines an estimate and its uncertainty to show a range of values compatible with the data under specified assumptions. No standard errors, confidence intervals, or numerical least-squares means for the primary endpoint are reported in the registry record.
How should the sequence be considered?
The design is identified as a single-group, open-label, two-period fixed-sequence trial. The recorded sequence gives BI 409306 without rifampicin first, followed by BI 409306 after rifampicin pretreatment. Allocation is not applicable and masking is none. Thus, this is not a randomized parallel-arm comparison. In general, fixed order means that treatment condition and period occur together in a particular sequence. Potential period or sequence influences are relevant considerations when interpreting a contrast, but the registry record does not report a model or analysis addressing them.
The sample-size illustrations use equal allocation between two arms and a normal approximation. Those assumptions do not match the recorded single-group fixed sequence as a description of how participants were assigned. The illustrations are planning calculations tied to fractions of an observed effect, not observed power. The trial’s own sample-size justification is not reported in the registry record, and the primary observed effect is also not reported.
What do sampling and outcome definitions contribute?
The primary outcome timeframe includes measurements within 3 hours (h) before administration and at 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, and 24h after administration. In general, the sampling schedule determines which portions of the concentration-time profile are observed directly. AUC0-tz uses the observed profile only through its last quantifiable point, while an extrapolated endpoint relies additionally on an estimate beyond observed quantifiable concentrations. The record gives the outcome definition and timeframe but not the resulting concentration measurements or exposure estimates.
The stated secondary objective was to evaluate and compare several pharmacokinetic parameters using descriptive statistics. AUC0-∞ is the named secondary outcome in the registry record. The record reports three outcome measures and three analyses, but does not identify all measures or provide their numerical results. It also does not report whether inferential comparisons were made for those secondary outcomes.
What cannot be established from the statistical record?
The registry record does not report the full statistical analysis plan, the exact model, missing-data procedures, imputation methods, handling of values below quantification limits, or any interim analyses. It does not report a p-value or confidence interval for the primary comparison. These omissions prevent a detailed assessment of the inferential procedure and of how uncertainty was handled. In general, such details help readers determine what data entered an analysis, which assumptions were used, and how planned comparisons were distinguished from exploratory ones. Their absence does not establish that a particular method was or was not used; it means the method is not documented in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists three outcome measures and three analyses. It names AUC0-∞ as a secondary outcome, while the primary outcome is AUC0-tz. The other outcome measures are not identified in the record. The record says secondary objectives were to be assessed using descriptive statistics, but does not report the numerical results or specify whether any formal testing was conducted for secondary outcomes.
Multiplicity arises in general when several outcomes or hypotheses are examined: the more comparisons considered, the greater the opportunity for chance findings if each is interpreted separately. Statistical approaches can account for multiple testing, but the registry record does not report a multiplicity adjustment or a hierarchy for interpreting outcomes. It is therefore not possible to determine whether or how multiplicity was addressed.
The primary analysis population is defined as the pharmacokinetic parameter analysis set. It includes subjects in the TS who provided at least one primary or secondary pharmacokinetic parameter not flagged for exclusion due to a protocol violation relevant to pharmacokinetic evaluation or due to pharmacokinetic non-evaluability. The registry record does not explain the abbreviation TS, report the number of participants in this analysis set, or give the number included in each endpoint analysis.
Missing-data handling is not reported in the registry record. No imputation method, rule for incomplete concentration profiles, or sensitivity analysis is described. Interim analyses and the statistical plan are also not reported in the registry record. These gaps limit assessment of whether the analysis followed prespecified procedures and how incomplete or unevaluable pharmacokinetic data affected the results.
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 |
|---|---|---|---|
| R: BI 409306 | 0 | 15 | 0.0% |
| Test Treatment, T: Rifampicin Pretreatment | 0 | 15 | 0.0% |
| Test Treatment, T: BI 409306 Subsequent to Rifampicin Pretreatment | 0 | 15 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| R: BI 409306 | 0 of 15 |
| Test Treatment, T: Rifampicin Pretreatment | 0 of 15 |
| Test Treatment, T: BI 409306 Subsequent to Rifampicin Pretreatment | 0 of 15 |
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 |
|---|---|
| R: BI 409306 | 1 of 15 |
| Test Treatment, T: Rifampicin Pretreatment | 15 of 15 |
| Test Treatment, T: BI 409306 Subsequent to Rifampicin Pretreatment | 1 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | R: BI 409306 | Test Treatment, T: Rifampicin Pretreatment | Test Treatment, T: BI 409306 Subsequent to Rifampicin Pretreatment |
|---|---|---|---|---|
| Chromaturia | Renal and urinary disorders | 0 of 15 | 15 of 15 | 0 of 15 |
| Headache | Nervous system disorders | 0 of 15 | 1 of 15 | 1 of 15 |
| Photopsia | Eye disorders | 1 of 15 | 0 of 15 | 0 of 15 |
| Haematoma | Vascular disorders | 0 of 15 | 1 of 15 | 0 of 15 |
The registry record reports serious adverse events for three treatment group entries, each with 15 participants at risk. It reports 0 participants affected by serious adverse events in the reference BI 409306 group, the rifampicin pretreatment group, and the BI 409306 following rifampicin pretreatment group. Deaths are recorded as 0 in each group. No serious adverse event terms are listed in the registry record.
For other adverse events, the record reports 1 affected participant among 15 at risk in the reference BI 409306 group, 15 among 15 in the rifampicin pretreatment group, and 1 among 15 in the BI 409306 following rifampicin pretreatment group. These are registry counts for the listed group entries; they do not indicate event severity beyond the distinction between serious and other events. The record does not provide event descriptions or further detail in the registry record reported.
In general, adverse-event counts describe what was recorded in the study and should be read in the context of the group definitions, observation periods, and data collection methods. The registry record does not provide enough detail to compare risks or attribute events to a particular treatment. The figures are not a substitute for the missing pharmacokinetic results and do not establish a causal explanation for events.
12. What the Result Does, and Does Not, Mean
This record documents a phase 1 pharmacokinetic trial asking whether prior rifampicin changes the relative bioavailability of BI 409306 in healthy male subjects. It specifies a primary measure, AUC0-tz, and identifies a fixed order of reference treatment followed by rifampicin pretreatment and BI 409306. Those design details establish the intended question and the conditions under which the comparison was planned.
The result itself cannot be characterized from the registry record because no primary endpoint estimate, standard error, confidence interval, or numerical comparison is reported. The direction, magnitude, and precision of the observed pharmacokinetic difference are therefore unknown from the posted results. The named secondary outcome AUC0-∞ also has no numerical result in the registry record. No conclusion about the direction or size of a pharmacokinetic change should be inferred from the objective or endpoint definition alone.
In general, pharmacokinetic exposure measures describe drug concentrations over time. They do not by themselves establish a clinical benefit or harm. This trial enrolled healthy male subjects and does not report a clinical outcome that would answer a treatment-effect question in patients. The registry information therefore supports description of the study question and methods, but not a clinical conclusion.
The fixed sequence and lack of random allocation are also relevant to what the design can establish. The record does not describe randomized treatment order, and it does not report how period or sequence effects were handled analytically. Without the results and model details, it is not possible to evaluate how those features influenced the estimated comparison.
The sample-size illustrations are planning tools based on stated assumptions and fractions of an observed effect. They are not observed power and cannot fill the gap left by unreported endpoint results. Overall, the record identifies the intended pharmacokinetic comparison but does not provide enough numerical evidence to quantify or interpret its result.
13. Why This Trial Matters Statistically
This trial is statistically notable because its question is a within-sequence pharmacokinetic comparison rather than a conventional randomized parallel-group contrast. The registry identifies a single-group, two-period fixed sequence: BI 409306 reference treatment first, followed by BI 409306 after rifampicin pretreatment. Recognizing that structure helps prevent readers from treating the conditions as independently randomized arms.
The primary endpoint is AUC0-tz, a continuous measure of exposure defined over the observed quantifiable interval. The endpoint definition and sampling schedule communicate what was intended to be measured, while the least-squares mean and standard error specify the kinds of summary statistics registered. Yet the registry record does not report the estimates or their uncertainty. This makes the distinction between a registered analysis and a reported result especially important: a well-defined question does not reveal the answer when the result is absent.
The record also illustrates why design and analysis details matter together. A fixed order makes period and sequence context relevant, while the model specification is not reported. The population definition gives eligibility criteria for the pharmacokinetic analysis set, but the number analyzed is absent. Without these details and the endpoint values, readers cannot judge the precision of the comparison or assess how exclusions and incomplete data affected it.
Finally, planning illustrations should be kept separate from observed evidence. The stated assumptions use equal allocation between two arms, although the registered design is a single-group fixed sequence. Such calculations can illustrate planning under their assumptions, but they do not establish observed power or a result for this trial. The statistical lesson is to distinguish study objectives, design features, planned assumptions, and numerical findings.
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 most important trial-specific limitation in interpreting the posted results is that the primary endpoint estimate is not reported in the registry record. The least-squares means, standard errors, confidence intervals, and numerical comparison are absent. This prevents assessment of both the estimated effect and its precision. The record likewise does not provide numerical results for the named secondary outcome, AUC0-∞.
The study enrolled 15 healthy male subjects and used a fixed treatment sequence without masking. Allocation is recorded as not applicable, so the design is not a randomized comparison of treatment order. The registry record does not describe adjustment for period or sequence effects. These design characteristics constrain interpretation of any comparison, although the absent numerical results preclude judging their practical influence.
The record does not state the number of participants in the pharmacokinetic analysis set or the number contributing to each outcome. It gives an analysis-population definition involving pharmacokinetic data availability and exclusions, but missing-data handling, sensitivity analyses, and treatment of non-evaluable measurements are not reported. The regimen description is truncated, limiting detail about the second-period administration.
The registry record lists three outcome measures and three analyses, but does not identify every measure or describe multiplicity control. It also does not report the full statistical model, an analysis plan, interim analyses, or the trial’s sample-size justification. These gaps limit reproducibility and evaluation of prespecification. The results should therefore be interpreted as insufficiently documented for quantitative assessment, not as evidence of a particular pharmacokinetic outcome.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Drug-drug Interaction Trial Between Rifampicin and BI 409306 in Healthy Volunteers — NCT03151499.
- Registry record last updated 2024-03-07; status last verified 2023-08.
- Results first posted 2024-03-07.
- 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.
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18. Record Summary
NCT03151499 is a completed phase 1, open-label, single-group, two-period fixed-sequence trial sponsored by Boehringer Ingelheim. It enrolled 15 healthy male subjects. The registered sequence compared BI 409306 without prior rifampicin with BI 409306 after rifampicin pretreatment.
The primary outcome was plasma AUC0-tz, described as a least-squares mean with standard error. AUC0-∞ was listed as a secondary outcome. The registry record does not report numerical pharmacokinetic estimates or uncertainty measures, and does not state how many participants contributed to the endpoint analysis. Serious adverse events and deaths were recorded as 0 in each of the three group entries, while other adverse events were recorded for 1, 15, and 1 participants, respectively.
The record defines the study question and provides design and endpoint details, but it does not provide the primary numerical results, a full statistical model, or missing-data and multiplicity procedures. The trial’s observed pharmacokinetic comparison cannot be quantified from the posted results.