Effectiveness of Two Different Doses of BI 1026706 on the Overall Peak-to-Peak (PtP) N2/P2-component Amplitude of Laser (Somatosensory, Radiant-heat) Evoked Potentials (LEP) in UVB(Ultraviolet)-Irradiated Skin in Healthy Male Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Two Different Doses of BI 1026706 on the Overall Peak-to-Peak (PtP) N2/P2-component Amplitude of Laser (Somatosensory, Radiant-heat) Evoked Potentials (LEP) in UVB(Ultraviolet)-Irradiated Skin in Healthy Male Volunteers (NCT02037165), a randomized phase 1 study. The primary outcome is Overall Peak-to-Peak(PtP) N2/P2-component Amplitude of Laser (Somatosensory/Radiant Heat) Evoked Potentials (LEP) in Ultraviolet B (UVB) -Irradiated Skin.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, single-blinded, placebo-controlled, single-dose, five-way crossover study. Enrollment was 25, and the listed population was healthy male volunteers. The study began on 2014-01-21, reached primary completion on 2014-04-09, and is listed as completed. Boehringer Ingelheim is named as sponsor.

The five treatment conditions were BI 1026706 at two doses, placebo, celecoxib, and pregabalin. The registry's treatment descriptions indicate that BI 1026706 treatment conditions used matching placebo and that active comparator treatments also used matching placebo to BI 1026706. The adverse-event groups identify the dose labels as 50 mg BI 1026706, 200 mg BI 1026706, 200 mg Celecoxib, and 150 mg Pregabalin.

In a crossover design, participants receive more than one treatment condition in different periods, so comparisons can be made within participants. This general design feature may reduce the influence of stable differences between participants. It also makes the interpretation dependent on period order and on whether effects from a previous treatment persist into a later period. The sequence allocation, period schedule, washout arrangements, and statistical handling of period or carryover effects are not reported in the registry record.

Single-blinding means some aspect of treatment assignment was masked, but the identity of the blinded parties and the masking procedures are not reported in the registry record. The registry describes the study as randomized; details of sequence generation and allocation concealment are not reported. The primary endpoint was measured repeatedly over the stated timeframe. The planned approach to analysing those repeated measurements is 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.

Period 1 (2 Days)

Washout Period 1 (6 Days)

Period 2 (2 Days)

Washout Period 2 (6 Days)

Analysis population for the primary outcome, as defined in the registry: pharmacodynamic set(PDS): included all subjects from the TS who provided in any treatment period a baseline value and at least 1 PD profile post drug administration for the primary or secondary PD endpoint, which was considered evaluable, and without (important) protocol violation(s) with respect to the statistical evaluation of PD endpoints.

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) : all subjects who were dispensed study medication and were documented to have taken at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Overall Peak-to-Peak(PtP) N2/P2-component Amplitude of Laser (Somatosensory/Radiant Heat) Evoked Potentials (LEP) in Ultraviolet B (UVB) -Irradiated Skin, measured over up to 24 hours (h): -2:05h, 0:30h, 1:00h, 2:00h, 3:00h, 4:00h, 5:00h, 6:00h, 22:00h, 24:00h (relative to study drug administration [h:min]).

The primary endpoint was the overall peak-to-peak N2/P2-component amplitude of laser-evoked potentials in UVB-irradiated skin, measured in microvolts (µv). The registry describes laser stimulation as somatosensory or radiant heat and lists the endpoint as a mean with standard deviation. The measurement schedule extended up to 24 hours relative to study drug administration, with listed times of -2:05h, 0:30h, 1:00h, 2:00h, 3:00h, 4:00h, 5:00h, 6:00h, 22:00h, and 24:00h.

In general, an evoked potential records an electrical response associated with a stimulus. Peak-to-peak amplitude expresses the size of the response between the named waveform components. In this study, the endpoint was a physiological measurement of response to laser stimulation in UVB-irradiated skin, rather than a direct report of pain intensity or a clinical outcome.

Such a measure can be used to assess pharmacodynamic effects under controlled study conditions. Its interpretation depends on how the endpoint is defined, when it is measured, and how repeated observations are analysed. The registry record does not report a single summary comparison across the measurement times, the numerical mean and standard deviation results, or an estimate of the treatment contrast. It therefore does not establish the size or precision of a primary-endpoint difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the reported endpoint summary mean?

The primary endpoint is classified as a continuous measure summarized by a mean, with standard deviation as the dispersion measure. In general, a mean describes the central value of a set of observations, while a standard deviation describes how dispersed observations are around that mean. The standard deviation is not the same as the uncertainty in a treatment-effect estimate. An uncertainty interval for a treatment contrast would describe precision in that contrast; no such interval is reported for the primary endpoint in the registry record.

The endpoint was assessed at multiple scheduled times, from -2:05h to 24:00h relative to study drug administration. In general, repeated observations on the same participant are related rather than independent. A statistical analysis should account for that dependence and specify how treatment, time, and any relevant design features are handled. The registry record does not report the model or other method used for the primary endpoint, nor does it report a single primary comparison.

Why does the crossover design matter?

In general, a crossover study compares treatments within participants across different treatment periods. Within-participant comparisons can account for stable characteristics that differ between people. Interpretation also depends on period effects, treatment sequence, and possible carryover from one period to another. A period effect is a change associated with when a measurement occurs; carryover refers to a lingering effect from an earlier treatment period. These are general design considerations, not claims that such effects occurred in this study. The registry record does not report the treatment sequence, washout arrangements, or the analysis used to address period or carryover effects.

Randomization can help balance treatment order, but the record does not describe sequence generation or allocation concealment. The study is labelled single-blinded, while the identity of the blinded parties and the procedures for maintaining masking are not reported in the registry record. These details matter when assessing how treatment assignment and outcome measurement might have influenced the observations.

How should uncertainty and significance be understood?

In general, a confidence interval communicates the uncertainty around an estimate under a specified statistical model. A p-value addresses how compatible data are with a stated null hypothesis under the assumptions of a test; it does not measure the probability that a treatment effect is true. Neither can be interpreted for the primary endpoint without a reported estimate and inferential result. The registry record does not report the primary endpoint's numerical results, confidence interval, or p-value.

The stated sample-size assumptions for planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations are based on fractions of an observed effect, rather than being the trial's own design justification. They are planning illustrations, not observed power. The sample-size justification for the trial is not reported in the registry record. No planning-illustration result can be treated as a result of the crossover trial itself.

What does multiplicity mean for this study?

In general, testing many endpoints, treatment contrasts, or time points can increase the chance of obtaining apparently notable results by chance. The registry lists 9 outcome measures and 162 analyses. Those counts indicate a broad set of outcomes and analyses, but the record does not explain how the analyses map to specific hypotheses or whether they were confirmatory, exploratory, or otherwise grouped. The statistical plan for controlling or addressing multiplicity is not reported in the registry record. The primary endpoint is not reduced to one comparison in the recorded results, so the primary question cannot be resolved by treating an unspecified analysis as definitive.

What analysis population is described?

The primary endpoint description refers to a treated set and a pharmacodynamic set. The latter is described as including subjects from the treated set who provided a baseline value in any treatment period and at least one evaluable post-drug pharmacodynamic profile for a primary or secondary endpoint, without important protocol violations with respect to criteria whose wording is incomplete in the registry record. This description gives some eligibility features but not the full definition. The numbers included in each analysis population and the handling of missing observations are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 9 outcome measures and 162 analyses. The primary endpoint itself was assessed at multiple scheduled times, and the posted primary-outcome information is not reduced to one comparison. When many outcomes, contrasts, or time points are examined, multiplicity is a general concern: the chance of a seemingly notable finding can increase when results are selected from many analyses. The registry record does not report a multiplicity adjustment, a hierarchy of hypotheses, or a distinction between confirmatory and exploratory analyses. The relationship between the listed analyses and any prespecified testing plan is not reported.

The primary endpoint description names a treated set and a pharmacodynamic set. The pharmacodynamic set is described as including participants from the treated set with a baseline value in any treatment period and at least one evaluable post-drug profile for a primary or secondary pharmacodynamic endpoint, subject to protocol-violation criteria. The description ends before fully specifying those criteria. Counts for the treated set and pharmacodynamic set, as well as the number contributing to each endpoint and time, are not reported in the registry record.

Missing-data handling is also not reported in the registry record. This includes whether missing observations were excluded, imputed, or addressed by a model, and how participants with incomplete treatment periods were handled. In general, missingness can affect both the precision and interpretation of results, particularly when analysis inclusion depends on having evaluable measurements. Without the analysis populations, missingness details, and a stated statistical approach, the degree to which the endpoint results represent all enrolled participants cannot be assessed from the registry record.

11. 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 events as affecting 0 participants in each safety group. The numbers at risk for serious adverse events are 25 for placebo, 24 for 50 mg BI 1026706, 25 for 200 mg BI 1026706, 25 for 200 mg Celecoxib, and 25 for 150 mg Pregabalin. These are group-specific figures; they should not be added together to describe unique participants in a crossover study.

The record lists no serious-event terms among its top serious terms. The deaths field is null for each group, so deaths are not reported in the registry record; a null entry should not be read as a reported zero. The record also lists other adverse events affecting 3 participants with placebo, 2 with 50 mg BI 1026706, 3 with 200 mg BI 1026706, 2 with 200 mg Celecoxib, and 17 with 150 mg Pregabalin. These are separate non-serious-event figures and do not change the serious-event counts.

In general, adverse-event counts describe events recorded under the registry's reporting definitions and observation period. The registry record does not provide further details about event types, severity criteria, exposure time, or the method of collection. These figures alone do not establish comparative risk or explain why events occurred.

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

The study was designed to examine pharmacodynamic responses to BI 1026706 in healthy male volunteers, using laser-evoked potential amplitude in UVB-irradiated skin as its primary endpoint. It also included active comparator treatments and other objectives, including capsaicin-related outcomes, pharmacokinetics, safety, and tolerability. This context describes the scope of the investigation; it does not establish a clinical benefit or harm.

The registry record does not report a single primary-outcome comparison or its numerical results. It is therefore not possible to determine from this record the direction, size, or precision of the primary treatment contrast. The absence of a reported result is not evidence that treatments were equivalent, and it is not evidence that an effect was present. No conclusion about treatment effect follows from the design description alone.

In general, a physiological endpoint can be useful for studying a response under controlled conditions, but it is not automatically interchangeable with a symptom or clinical outcome. The primary endpoint was an evoked-potential amplitude measured in a specified skin condition. The secondary outcomes included other physiological measures and visual analogue scales, but their results are not detailed in the registry record. The relationship between this endpoint and outcomes that matter to patients is not reported in the registry record.

The population and setting also define the scope of the evidence. The study concerned healthy male volunteers and was listed as Phase 1. Its findings, if reported, would need to be interpreted in relation to that study population and the experimental conditions. The record does not provide a basis for generalizing beyond those conditions or for making medical decisions. The statistical information available supports describing the study design and endpoint, but not a conclusion that BI 1026706 does or does not work.

13. Why This Trial Matters Statistically

This study is statistically notable for combining a randomized crossover design with a repeated-measure pharmacodynamic endpoint. In general, crossover designs can make within-participant comparisons, while repeated measurements can describe changes over time. Both features require a clear account of how observations are related and how treatment and time are represented in the analysis. The registry record does not report the model or method used for those analyses, making the intended handling of these design features difficult to assess.

The endpoint was recorded at multiple times, but the primary outcome is not reduced to one comparison in the registry record. That distinction matters: a schedule of measurements is not itself a treatment-effect estimate. A clear summary should identify the target contrast and explain how the time-specific observations contribute to it. Without that summary and its uncertainty, readers cannot assess the magnitude or precision of the primary result.

The record also lists 9 outcome measures and 162 analyses. In general, a large analysis set raises questions about prespecification, interpretation, and multiplicity. The registry record does not report whether or how those issues were addressed. This does not show that the analyses were inappropriate; it means the analysis plan and its relationship to the reported results are not documented in the record.

Finally, the record illustrates why a completed study and a detailed design description are not substitutes for accessible outcome estimates. The enrollment, treatment conditions, endpoint definition, and safety counts provide useful context. Yet the primary treatment comparison and the handling of missing data and analysis populations are not reported. Those omissions limit statistical interpretation independently of the study's design.

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.

Several limitations specific to this study affect interpretation of the primary endpoint. The registry record does not report a single primary-outcome comparison, numerical endpoint results, an estimate of the treatment contrast, or its uncertainty. The endpoint was measured at multiple scheduled times, but the method for summarizing or modelling those repeated observations is not reported. As a result, neither the size nor the precision of the primary effect can be assessed from the record.

The study used a five-way crossover design, but the treatment sequence, period schedule, washout arrangements, and handling of period or carryover effects are not reported in the registry record. These are relevant details for understanding within-participant comparisons. The record identifies the study as randomized and single-blinded but does not describe sequence generation, allocation concealment, who was blinded, or how masking was maintained.

The primary-endpoint population description is incomplete. It refers to a pharmacodynamic set requiring a baseline and at least one evaluable post-drug profile, along with protocol-violation criteria, but the full criteria are not reported. Analysis-population counts, missing-data methods, and reasons for any exclusions are not reported in the registry record. The relationship between the 162 analyses and any prespecified statistical plan is also not explained, and multiplicity handling is not reported.

Finally, the study population was healthy male volunteers, and the primary measure was a physiological response in UVB-irradiated skin. Those features constrain the setting to which any findings could apply. The registry record does not report a primary result that would permit assessment of the endpoint's observed response in this trial.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness of Two Different Doses of BI 1026706 on the Overall Peak-to-Peak (PtP) N2/P2-component Amplitude of Laser (Somatosensory, Radiant-heat) Evoked Potentials (LEP) in UVB(Ultraviolet)-Irradiated Skin in Healthy Male Volunteers — NCT02037165.
• Registry record last updated 2019-07-05; status last verified 2019-04.
• Results first posted 2019-07-05.
• 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

NCT02037165 is a completed Phase 1 randomized, single-blinded, placebo-controlled, single-dose, five-way crossover study sponsored by Boehringer Ingelheim. Enrollment was 25, and the study population was healthy male volunteers. The study began on 2014-01-21 and reached primary completion on 2014-04-09.

The primary endpoint was mean overall peak-to-peak N2/P2-component amplitude of laser-evoked potentials in UVB-irradiated skin, measured in microvolts (µv), at scheduled times up to 24 hours. Treatment conditions included two BI 1026706 doses, placebo, celecoxib, and pregabalin. The record lists 9 outcome measures and 162 analyses.

The registry record does not report a single primary-outcome comparison, numerical primary endpoint results, or the statistical approach for repeated measurements. Serious adverse events affected 0 participants in each listed safety group; deaths are not reported in the registry record. The recorded design and safety information provide context, but do not establish a primary treatment effect.