A Study in Healthy People to Test How 2 Different Formulations of BI 695501 Are Taken up by the Body When Given as an Injection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Healthy People to Test How 2 Different Formulations of BI 695501 Are Taken up by the Body When Given as an Injection (NCT05203289), a randomized phase 1 study. The primary outcome is Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 to 1344 Hours After Dose Administration (AUC0-1344).

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, quadruple-masked, parallel-arm study in healthy people. The registry lists an enrollment of 200 and describes the trial as completed. Its stated start date was 2022-02-18, and its primary completion date was 2022-08-29. Boehringer Ingelheim is listed as the sponsor.

Participants were assigned to a single subcutaneous dose of either BI 695501 40 mg/0.4 mL, the test treatment, or BI 695501 40 mg/0.8 mL, the reference treatment. The official title identifies both male and female subjects. The registry characterizes the study as double blind in that title and separately lists quadruple masking. It does not explain which groups of people were masked or how masking was maintained.

The primary objective was pharmacokinetic comparison, not evaluation of a disease-related clinical endpoint. Plasma concentrations were scheduled for measurement within 1 hour before dosing and at 4, 12, 24, 48, 72, 96, 120, 144, 168, 216, 336, 504, 672, 840, 1008 and 1344 hours after drug administration. The primary endpoint uses measurements over the interval from 0 to 1344 hours.

The pharmacokinetic results include 93 participants in the test arm and 99 in the reference arm. The safety summaries use denominators of 99 and 101, respectively. These are different analysis summaries; the registry record does not explain the reasons for the differences. Randomization, masking, and the parallel-arm structure describe the design, but do not by themselves establish that the compared formulations meet a particular equivalence criterion.

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 prior to participation in the trials. There was no run-in period and subjects did not have to attend a specialist site. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic analysis set (PKS): The pharmacokinetic set consisted of all randomized subjects who received the single dose of trial medication, and had at least one evaluable primary pharmacokinetics (PK) parameter, and were without important protocol deviations or violations thought to have a relevant impact on the PK of BI 695501. Only participants with evaluable results for this PK parameter are reported.

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: All subjects randomized set (RND): All subjects randomized set contained all subjects who provided informed consent for this study (all subjects enrolled set (ENR)) and were randomized to trial medication.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 to 1344 Hours After Dose Administration (AUC0-1344), measured over BI 695501 was measured within 1 hour before and 4, 12, 24, 48, 72, 96, 120, 144, 168, 216, 336, 504, 672, 840, 1008 and 1344 hours after drug administration..

The primary endpoint is the area under the plasma concentration-time curve of BI 695501 from 0 to 1344 hours after dosing, abbreviated AUC0-1344. AUC represents drug exposure across the measured period: it incorporates concentration measurements over time rather than relying on a single blood sample. The registry reports it in microgram * hours / milliliter.

For this study, exposure is relevant because the objective was to compare how much BI 695501 entered the body after administration of the two formulations. AUC is commonly used in pharmacokinetic comparisons because it summarizes concentration over a defined time interval. The time interval matters: the endpoint concerns exposure through 1344 hours, not exposure over an unspecified or unlimited period.

The registry reports adjusted geometric least-squares means for each arm. The model was applied on the logarithmic scale and included fixed effects for treatment, location of trial medication injection, and baseline body weight. The reported dispersion is the geometric coefficient of variation. These statistics describe the pharmacokinetic analysis; they are not direct measures of symptom improvement, disease control, or other clinical benefit.

The registry does not report a prespecified acceptance range for the ratio or identify a decision rule for equivalence. The endpoint and its estimate can therefore be described as a comparison of measured exposure, but the ratio alone should not be treated as proof that the formulations are equivalent under a particular regulatory or clinical standard.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis is a comparison of pharmacokinetic exposure between randomized parallel arms. The outcome is AUC0-1344, and the record reports adjusted geometric least-squares means, a ratio of geometric means, and a 90% confidence interval. Understanding the scale and adjustment helps clarify what these statistics mean.

Why use a geometric scale?

Pharmacokinetic measurements are often analyzed on a logarithmic scale because exposure values can be asymmetric and because ratios are often the relevant comparison. On a log scale, multiplicative differences are represented as additive differences, which can suit an analysis of covariance. After estimation on that scale, results can be expressed as geometric means and a ratio of geometric means.

A ratio answers a different question from a difference. It describes the test-arm geometric mean relative to the reference-arm geometric mean, expressed as a percentage. A ratio of 100% corresponds to equal geometric means. Ratios above or below that value indicate the direction of the estimated relative exposure; they do not, without a prespecified criterion, determine whether a difference is important or whether equivalence has been established.

What does the adjustment do?

The registry says that the presented means were adjusted using an analysis of covariance model on the logarithmic scale. The model included fixed effects for treatment, location of trial medication injection, and baseline body weight. In general, adjustment estimates the treatment comparison while accounting for the listed model terms. It does not mean that the estimate is free of all possible bias, nor does it show that every relevant factor was measured and included.

The adjusted geometric least-squares means are model-based summaries. They need not match unadjusted summaries calculated directly from participant-level outcomes. The reported ratio and interval are the sponsor’s stated analysis results; they should not be reconstructed by taking a ratio of rounded arm summaries. The registry does not provide enough participant-level information to reproduce the fitted model independently.

How should the confidence interval be read?

A confidence interval conveys uncertainty about an estimated quantity under the analysis assumptions. A narrower interval indicates greater precision than a wider interval, while the point estimate marks the central reported estimate. The 90% confidence interval for the ratio is 93.31% to 111.23%. It describes uncertainty about the ratio, not the spread of individual participants’ AUC values.

For an equivalence assessment, interpretation usually depends on comparing the confidence interval with prespecified bounds. The registry does not report such bounds or a formal equivalence decision rule. Consequently, the interval’s relation to 100% can be described, but a formal equivalence conclusion cannot be derived from the registry entries alone. The registry also gives no p-value for this primary comparison.

What does geometric coefficient of variation describe?

The geometric coefficient of variation is a measure of variability on a multiplicative, geometric scale. It helps characterize dispersion in pharmacokinetic measurements when values are analyzed after logarithmic transformation. The reported value is 37.6% in each arm. It is not a confidence interval, is not the percentage difference between treatment means, and does not indicate that each participant’s value falls within a particular range.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. When variability is underrepresented, uncertainty may be understated and intervals may be too narrow. This is a general statistical concern, not a finding reported for this study. The record gives geometric coefficients of variation but does not report an over-dispersion assessment or a method specifically addressing it.

What can the analysis say about the design?

Randomization supports a planned comparison between the assigned formulations, while the parallel-arm structure means participants received a treatment in one arm rather than crossing over between formulations. Masking can reduce some forms of influence on study conduct and assessment. These design features do not replace examination of the analysis population, missing observations, protocol deviations, or the prespecified analysis plan. Details of those procedures are not reported in the registry record beyond the partial description of the pharmacokinetic analysis set.

The assumptions listed for the separate planning illustrations are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence about the study’s actual design justification. Specific planning results are not reported in the registry record summarized in this analysis.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as an adjusted ratio of geometric means of 101.88%, with a 90% confidence interval from 93.31% to 111.23%. This is the reported inferential result for the primary endpoint. The arm-level adjusted means are 1415 for the test formulation and 1389 for the reference formulation, with geometric coefficients of variation of 37.6% in both arms.

The registry record does not report a separate recalculated ratio or confidence interval that can be compared numerically with the sponsor’s analysis. The arm summaries alone are not sufficient to reproduce the adjusted model, which includes treatment, injection location, and baseline body weight on the logarithmic scale. A calculation based only on rounded summaries would not replace the model-based sponsor result.

The registry does not flag a discrepancy between the reported analysis and a recalculation. That does not amount to an independent reproduction of the model. The sponsor’s reported estimate and interval therefore remain the available analysis for interpretation. The record does not report the equivalence bounds or a formal decision rule, so the sponsor’s numerical result should be read as an exposure estimate with stated uncertainty rather than as a documented equivalence determination.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies AUC0-1344 as the primary outcome measure and reports a primary comparison. It lists zero posted secondary outcome measures. Although the record indicates three outcome measures and three analyses overall, the additional endpoint details and results are not available in the registry record for this interpretation. No multiplicity adjustment or hierarchy for testing multiple outcomes is reported in the registry record.

Multiplicity matters when several outcomes or comparisons are tested, because repeated testing can increase the chance of a false-positive result. A prespecified testing strategy can address that concern, but the registry record does not report such a strategy. The absence of a reported adjustment should not be taken to mean that an adjustment was or was not used outside the information in the record.

The record describes a pharmacokinetic analysis set that includes randomized participants who received the single dose, had at least one evaluable primary pharmacokinetic parameter, and were without important protocol deviations or violations thought to have an effect. The final clause of that description is incomplete in the registry record. The record does not report a full accounting of exclusions from this set, the handling of missing concentrations, or the approach to incomplete concentration-time profiles.

The pharmacokinetic results include 93 participants in the test arm and 99 in the reference arm. The safety summaries use 99 and 101 participants, respectively. These different denominators indicate that the reported analyses do not use the same group counts, but the reasons are not reported in the registry record. They should not be combined or treated as interchangeable.

The registry does not report the statistical plan, an interim analysis plan, or detailed sensitivity analyses for missing data and protocol deviations. Without those details, readers cannot assess whether the posted analysis follows a prespecified strategy or how robust it is to alternative population definitions. These are reporting limits, not evidence that a particular analysis procedure was omitted from the conduct of the trial.

12. 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 safety summary reports zero serious adverse events among 99 participants in the BI 695501 40 mg/0.4 mL arm and zero among 101 participants in the BI 695501 40 mg/0.8 mL arm. It also reports zero deaths in both arms. The record lists no top serious adverse event terms.

Other adverse events are reported for 6 of 99 participants in the test arm and 13 of 101 participants in the reference arm. These are the registry’s counts and denominators; they should not be interpreted as evidence of a causal difference between formulations. The registry record does not provide event-level descriptions for these other events in the registry record, or details about severity, timing, duration, or relationship to treatment.

Serious adverse events and other adverse events are distinct categories in the posted summary. A count of zero serious events does not establish that no adverse events occurred, as the separate other-event counts demonstrate. Conversely, counts of other events do not establish that the formulations differ in safety. The safety denominators also differ from the pharmacokinetic analysis counts, and the record does not explain why.

These figures describe reported events during the study; they do not establish safety in other populations or with repeated dosing. The trial involved healthy people and a single administration. The registry record does not provide enough detail to assess uncommon harms or to make a broad comparative safety conclusion.

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

The primary result describes systemic exposure following one subcutaneous administration of BI 695501 in healthy people. The adjusted ratio of geometric means was 101.88%, and its 90% confidence interval was 93.31% to 111.23%. Those values summarize the estimated relative AUC0-1344 and its statistical uncertainty under the reported model.

The result does not establish that the two formulations are equivalent under a particular standard. The registry record does not state the acceptance bounds, a formal equivalence decision rule, or a p-value for the primary comparison. A confidence interval that includes 100% is not by itself a test of equivalence. The interpretation depends on the prespecified criteria, which are not reported in the registry record.

The study also does not answer whether the formulations produce the same outcomes after repeated administration, in people with a medical condition, or in settings unlike this phase 1 study. Its population was healthy male and female subjects, and its primary endpoint was pharmacokinetic exposure rather than a measure of clinical benefit. No claim about symptom improvement or disease control follows from this endpoint.

The posted results do not establish that either formulation is preferable. The ratio is an estimate, and the interval communicates uncertainty; neither identifies the practical importance of any difference without a relevant, prespecified threshold. The reported geometric coefficient of variation describes variability on a geometric scale, but does not show how an individual participant’s exposure relates to the group estimate.

Safety results should be read in the same bounded way. The summary reports no serious adverse events or deaths in either arm, alongside the reported counts of other adverse events. These observations do not establish the absence of risk, nor do the counts alone show a causal safety difference. The study’s size, population, duration and single-dose design limit what can be inferred beyond the recorded observations.

14. Why This Trial Matters Statistically

This trial illustrates how a pharmacokinetic comparison can focus on exposure rather than a clinical outcome. AUC0-1344 integrates plasma concentration over a specified period, while the ratio of geometric means expresses the relative exposure between formulations. Those measures are suited to a formulation comparison, but their interpretation depends on the analysis scale and the prespecified decision criteria.

The study also shows why an estimate should be read together with its confidence interval. A point estimate near 100% does not convey the full uncertainty, and the interval does not supply an equivalence conclusion without prespecified bounds. Reporting both makes the precision of the comparison more transparent, while the absence of the acceptance criteria in the registry record leaves an important interpretive element unresolved.

Model adjustment is another important feature. The reported means account for treatment, injection location, and baseline body weight in an analysis on the logarithmic scale. These details make clear that the result is model-based, not simply a comparison of raw averages. They also demonstrate why rounded arm summaries cannot reproduce the sponsor’s adjusted estimate.

Finally, the trial highlights the importance of understanding analysis populations and denominators. Pharmacokinetic and safety summaries have different reported counts, and the registry does not explain the difference. Clear reporting of participant flow, missing measurements, and analysis-set exclusions would help readers assess how the estimates relate to the randomized study population. The record’s incomplete description of the pharmacokinetic set further limits that assessment.

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 primary outcome is a pharmacokinetic measure in healthy people after a single dose. It does not directly measure clinical benefit, and the study does not address repeated administration or people with a medical condition. The results should therefore be understood within the population, dose, route, and measurement period described in the registry record.

The registry reports an adjusted ratio and a 90% confidence interval but does not report acceptance bounds for a bioequivalence assessment or a formal decision rule. No p-value for the primary comparison is reported. Without the criteria used to interpret the interval, the numerical result cannot independently establish a formal equivalence conclusion.

The pharmacokinetic analysis counts are 93 in the test arm and 99 in the reference arm, while the safety denominators are 99 and 101. Reasons for the difference are not reported in the registry record. The record also does not provide a complete accounting of participant exclusions, missing measurements, or the handling of incomplete concentration-time data. Its description of the analysis population ends mid-clause.

The registry does not report the complete statistical analysis plan, multiplicity procedures, interim analyses, sensitivity analyses, or the rationale for the planned enrollment. The reported adjusted means and ratio cannot be independently reproduced from the arm summaries because the participant-level data and full model output are not reported. The geometric coefficients of variation describe dispersion but do not replace individual-level data or uncertainty measures for the arm-specific estimates.

The safety summary provides event counts and denominators but limited detail about the other adverse events. It does not, in the information summarized, provide event timing, severity, duration, or treatment relatedness. These limits restrict interpretation of both comparative safety and the range of harms that can be assessed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study in Healthy People to Test How 2 Different Formulations of BI 695501 Are Taken up by the Body When Given as an Injection — NCT05203289.
• Registry record last updated 2024-03-15; status last verified 2023-08.
• Results first posted 2024-03-15.
• 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.

19. Record Summary

NCT05203289 is a completed phase 1 randomized, quadruple-masked, parallel-arm study sponsored by Boehringer Ingelheim. It enrolled healthy male and female subjects and compared a single subcutaneous dose of BI 695501 40 mg/0.4 mL with BI 695501 40 mg/0.8 mL. The registry lists an enrollment of 200, a start date of 2022-02-18, and a primary completion date of 2022-08-29.

The primary endpoint was AUC0-1344 in plasma. The adjusted geometric least-squares means were 1415 and 1389 microgram * hours / milliliter, with geometric coefficients of variation of 37.6% in both arms. The reported ratio of geometric means was 101.88%, with a 90% confidence interval from 93.31% to 111.23%.

The registry does not report bioequivalence acceptance bounds, a formal decision rule, or a p-value for this comparison. Its safety summary reports zero serious adverse events and zero deaths in both arms, and other adverse events for 6 of 99 and 13 of 101 participants. The pharmacokinetic and safety denominators differ, and the reason is not reported.