Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 1015550 Powder for Oral Solution: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 1015550 Powder for Oral Solution (NCT01835899), a randomized phase 1 study. The primary outcome is Percentage of Subjects With Drug-related Adverse Events.

2. Clinical Question

3. Trial Design

The registry describes a completed, randomized, double-blind, parallel-group phase I trial sponsored by Boehringer Ingelheim. Its official title specifies multiple rising oral doses of BI 1015550 powder for oral solution in healthy male volunteers, once or twice daily for 14 days, with placebo control within dose groups. The trial’s stated purpose was to investigate safety, tolerability, and pharmacokinetics.

The registry lists enrollment of 24 participants. For the primary endpoint, the reported group sizes are 6 for placebo, 9 for 1 mg BI 1015550, and 9 for 6 mg BI 1015550. These group counts total the listed enrollment, but the record does not explain participant flow or give a separate accounting of withdrawals, exclusions, or missing outcome observations.

The registry lists the study as completed. The start is recorded as 2013-04 and primary completion as 2013-06. The primary endpoint’s stated timeframe runs from first drug administration until last drug administration, up to 18 days. The official title describes 14 days of treatment, but the registry record does not provide group-specific dosing schedules or clarify the timing of individual assessments.

The posted primary outcome concerns drug-related adverse events. Secondary outcomes listed in the record concern pharmacokinetic measures, including Cmax and several AUC measures. The registry lists no analyses for the outcome summary used here, and outcome values for the secondary measures are not reported in the registry record. Details of randomization implementation, concealment, and the statistical analysis plan 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: This study of multiple doses over 14 days was randomised, double-blind, and placebo-controlled within dose groups.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The treated set (TS) included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.

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: The treated set (TS) included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects With Drug-related Adverse Events, measured over From first drug administration until last drug administration, upto 18 days..

The primary endpoint is the percentage of participants with investigator-assessed drug-related adverse events. Its timeframe is from first drug administration until last drug administration, up to 18 days. The analysis population is the treated set: participants dispensed study medication and documented as having taken at least one dose of investigational treatment.

In general, a binary safety endpoint records whether a participant experienced at least one event meeting the endpoint definition during the specified observation period. Reporting a percentage makes the frequency easy to describe across treatment groups. It does not, by itself, convey the number, severity, duration, or clinical character of the events, nor does it establish that treatment caused them. The investigator’s assessment of drug relation is part of this endpoint’s definition.

The registry reports 16.7% for placebo, 44.4% for 1 mg BI 1015550, and 11.1% for 6 mg BI 1015550. It does not report confidence intervals for these percentages or a formal between-group analysis. The endpoint is relevant to the stated safety and tolerability purpose, while the separate pharmacokinetic outcomes address drug exposure. Those pharmacokinetic results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

For a binary outcome, each participant is classified according to whether the defined event occurred during the observation period. The group percentage summarizes the proportion classified with the event. Here, the endpoint is the percentage with investigator-assessed drug-related adverse events during the stated timeframe. It does not describe the total number of episodes per participant, and it does not by itself summarize event severity or duration.

As a general statistical concept, a percentage is an estimate based on the participants observed in that group. With small groups, the estimate can change noticeably if the outcome status of a participant changes. The record reports group sizes of 6, 9, and 9 and percentages of 16.7%, 44.4%, and 11.1%, respectively. Confidence intervals would communicate uncertainty around the estimates, but intervals are not reported in the registry record.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method. It helps readers assess precision rather than relying only on a point estimate. The registry record does not report confidence intervals for the primary percentages. No interval can therefore be used to assess the uncertainty around those specific results from the posted record.

A confidence interval for each group percentage would answer a different question from a confidence interval for a contrast between groups. The former concerns the uncertainty around an individual group estimate; the latter concerns the uncertainty around a difference or other comparison. Neither kind of interval is reported in the registry record for this endpoint. No comparison estimate or p-value is posted.

What can be inferred from the group pattern?

In general, an observed difference between group estimates can arise from a treatment effect, random variation, or other differences that the analysis does not account for. Randomization is intended to support fair comparisons, but the registry record does not report the allocation procedure or a model for analyzing this endpoint. The observed ordering of the percentages alone cannot distinguish among these possibilities. It should be described as the pattern in the posted data, not as proof of a dose-related trend.

The groups are small, and the outcome is a participant-level percentage. That means the estimates contain limited information about how frequently the event might occur in a broader population. The record does not post inferential results that would quantify the uncertainty of a treatment comparison. A reader should therefore avoid treating the visual or numerical separation among percentages as a settled effect.

What does the sample-size illustration mean?

In general, sample-size calculations estimate how many participants a future study might need to detect a specified effect under stated statistical assumptions. The registry record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes planning for a specified share of the observed effect. Such illustrations are planning exercises, not observed trial outcomes and not the study’s own sample-size justification.

The record does not report the trial’s sample-size justification or protocol calculations. It also does not report a completed inferential analysis of the primary endpoint. A planning illustration cannot establish that the trial had adequate power for a particular comparison, and it must not be described as observed power. The registry record does not contain enough information to evaluate the assumptions behind the trial’s original design.

Why do analysis choices matter?

In general, analysis choices include defining the population, handling missing outcomes, choosing a comparison method, and deciding how to address multiple outcomes or comparisons. Each can affect the interpretation of an estimate. The registry identifies the treated set for the primary endpoint, but it does not report a statistical analysis plan, missing-data method, or adjustment for multiple comparisons. Those details are not reported in the registry record.

The endpoint’s investigator assessment also matters: the reported outcome concerns events judged drug-related, rather than every adverse event. The separately posted serious and other adverse-event counts provide additional safety information, but they do not replace the endpoint or establish the same event classification. Without fuller analysis details and event-level descriptions, interpretation should remain close to the definitions and summaries actually posted.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Placebo to BI 1015550", "1 mg BI 1015550", "6 mg BI 1015550")
n      <- c(6, 9, 9)
events <- c(1, 4, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Placebo to BI 1015550  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  1 mg BI 1015550  9  4  44.4  13.7  78.8  18.9  73.3  18.7  73.8
ARM  6 mg BI 1015550  9  1  11.1  0.3  48.2  2.0  43.5  2.5  44.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five secondary outcomes: Cmax, AUCt,1, AUC0-infinity, Cmax,ss, and AUCt,ss. Their result values are not reported in the registry record. The record does not state whether these outcomes were analyzed with a prespecified hierarchy, whether any adjustment for multiple comparisons was planned, or how the primary and secondary outcomes were prioritized statistically. A multiplicity strategy is therefore not reported in the registry record.

In general, testing multiple outcomes or comparisons increases the chance that at least one result may appear notable by chance if each is interpreted separately. Methods for addressing this issue depend on the design and the intended claims. Because no inferential analyses are posted for the primary endpoint and the secondary outcome results are not present, the record does not permit an assessment of multiplicity handling or its impact on conclusions.

The primary endpoint population is defined as the treated set: participants dispensed study medication and documented to have taken at least one dose. The record does not report how many participants, if any, had missing primary outcome information, nor does it describe a method for handling missing data. It does not provide participant flow details or explain whether all treated participants contributed to the posted percentages.

The registry record also does not report an intention-to-treat analysis population, sensitivity analyses, or imputation methods. These absences limit assessment of whether the posted summaries could be affected by missing observations or exclusions. They do not establish that data were missing or that any particular handling method was used; those details are simply not reported in the registry record.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry lists serious adverse-event counts of 0 for placebo, 0 for 1 mg BI 1015550, and 0 for 6 mg BI 1015550. The corresponding numbers at risk are 6, 9, and 9. These are counts in the posted serious adverse-event grouping; the record does not list serious event terms.

The registry also lists other adverse-event counts of 1 for placebo, 4 for 1 mg BI 1015550, and 1 for 6 mg BI 1015550, with numbers at risk of 6, 9, and 9. These counts should not be read as the primary endpoint percentages: the primary endpoint is specifically the percentage of participants with investigator-assessed drug-related adverse events, while the adverse-event summary uses serious and other groupings. The record does not establish that all events in the other category were considered drug-related.

In general, a count of zero in a small group means that no event in that category was recorded for the observed participants; it does not establish that the event cannot occur. Death counts are not reported in the registry record. The posted figures do not include event descriptions or additional details needed to characterize severity, timing, or relationship for individual events.

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

The registry results show the percentages of treated participants recorded with investigator-assessed drug-related adverse events: 16.7% for placebo, 44.4% for 1 mg BI 1015550, and 11.1% for 6 mg BI 1015550. They also show group sizes of 6, 9, and 9. These are descriptive summaries of the reported groups during the stated observation period.

The figures do not establish that BI 1015550 caused the events or that the observed percentages represent a reproducible pattern. The endpoint depends on investigator assessment, and no formal comparison, confidence interval, or p-value is reported in the registry record. The small group sizes also mean that the percentages should not be treated as precise estimates for a wider population.

The results do not answer questions about participants outside the study population of healthy male volunteers, longer-term use, or outcomes not included in the posted results. The official title describes repeated dosing for 14 days, and the primary outcome timeframe extends up to 18 days. Broader exposure or other clinical settings are not characterized by these data.

The serious adverse-event summary lists 0 events in each group, while the other adverse-event summary lists 1, 4, and 1. Those counts are separate from the primary drug-related endpoint, and the registry does not provide event terms for the serious category. The absence of a listed serious event in these groups should not be interpreted as proof that serious events are impossible.

The registry’s secondary outcomes concern pharmacokinetics, but their result values are not reported in the registry record. As a result, the posted safety percentages cannot be linked to a reported exposure profile. The record supports a limited description of the observations, not a medical recommendation or a definitive treatment conclusion.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between a safety summary and a comparative efficacy-style claim. The primary endpoint is a participant-level percentage for investigator-assessed drug-related adverse events. That measure is useful for describing how many participants in each group met the endpoint definition during the observation period, but its interpretation depends on the event definition, assessment, and analysis population.

The group sizes are small: 6 for placebo and 9 in each of the two BI 1015550 groups. In general, percentages from small groups can be sensitive to the experience of individual participants. Reporting the percentages without confidence intervals or a formal comparison leaves the precision of the estimates unclear. This is an important statistical distinction: observed variation among groups is not automatically evidence of a true underlying difference.

The record also shows why endpoint labels matter. The primary outcome is drug-related adverse events, while the separate safety summary groups events as serious or other. Those summaries address related but nonidentical questions. Reading them together requires attention to their definitions rather than treating their counts as interchangeable.

Finally, the trial’s stated objectives include pharmacokinetics, but the listed secondary outcomes have no result values in the registry record. The contrast between listed objectives and available numerical results is relevant when assessing what a public trial record can support. The result is a bounded account of short-term observations in healthy male volunteers, not a complete statistical or clinical characterization.

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 endpoint percentages are reported without confidence intervals, a comparison estimate, or a p-value. The registry record therefore does not quantify uncertainty around the group estimates or the contrast between groups. The group sizes are 6, 9, and 9, so the summaries describe a limited number of participants.

The record defines the treated set but does not give participant flow, missing outcome counts, exclusions, or a missing-data method. It does not describe the statistical analysis plan, randomization implementation, allocation concealment, or any adjustment for multiple comparisons. These omissions prevent a full assessment of how the analyses were conducted.

The endpoint relies on investigator assessment of whether an adverse event was drug-related. The registry does not provide event-level descriptions for the primary outcome or serious adverse-event terms. The other adverse-event counts do not identify whether those events were judged drug-related. Death counts are not reported in the registry record.

The record lists pharmacokinetic secondary outcomes but does not report their results. It also does not report the trial’s sample-size justification. Planning illustrations based on an observed effect are not a substitute for the original design rationale or for an inferential analysis.

Finally, the population is healthy male volunteers, and the official title describes dosing for 14 days. The primary endpoint timeframe is up to 18 days. These features define the scope of the reported observations; results cannot be assumed to characterize different populations or longer periods of use.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 1015550 Powder for Oral Solution — NCT01835899.
• Registry record last updated 2016-01-22; status last verified 2015-12.
• Results first posted 2016-01-22.
• 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

NCT01835899 is a completed randomized, double-blind, parallel-group phase I trial sponsored by Boehringer Ingelheim. The official title describes multiple rising oral doses of BI 1015550 powder for oral solution, once or twice daily for 14 days, in healthy male volunteers, with placebo control within dose groups. Enrollment is listed as 24.

The primary endpoint is the percentage of participants with investigator-assessed drug-related adverse events from first administration until last administration, up to 18 days. The registry reports 16.7% for placebo, 44.4% for 1 mg BI 1015550, and 11.1% for 6 mg BI 1015550. The corresponding group sizes are 6, 9, and 9. No confidence intervals or formal comparison results are reported in the registry record.

The record lists five pharmacokinetic secondary outcomes but does not report their result values. Details of missing-data handling, multiplicity, and the trial’s sample-size justification are not reported in the registry record.