A Single-Center, Phase 2 Study Evaluating Bilastine Ophthalmic Solution in the CAC® Model: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Single-Center, Phase 2 Study Evaluating Bilastine Ophthalmic Solution in the CAC® Model (NCT03231969), a randomized phase 2 study. The primary outcome is Ocular Itching.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, vehicle-controlled phase 2 study at a single center. The registry record lists enrollment as 121 and status as completed. It lists four regimens: bilastine ophthalmic solution at 0.2%, 0.4%, and 0.6%, and bilastine 0%, described as vehicle. Each regimen's description specifies 1 drop in each eye at 3 separate times during a 25 day period.

The official title describes the study as double-masked, while the registry's masking classification is triple. The record does not explain this difference or specify which roles were masked. Allocation is listed as randomized, but the randomization sequence and allocation concealment procedures are not reported in the registry record.

The endpoint assessment used the Conjunctival Allergen Challenge (Ora-CAC) model. Ocular itching was assessed after challenge at Visit 4b (Day 1, 16h post treatment), Visit 5b (Day 15 ±3, 8h post treatment), and Visit 6 (Day 22 ±3, 15 minutes post treatment). The registry record gives start and primary completion dates, but dates alone do not establish how long each participant was followed.

Details such as eligibility criteria, baseline characteristics, treatment adherence, and the precise analysis population are not reported in the registry record. The record also does not give the number assigned to each regimen or explain whether every enrolled participant contributed data at every visit.

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.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Ocular Itching, measured over The outcome measure was assessed at Visit 4b (Day 1, 16h post treatment), Visit 5b (Day 15 ±3, 8h post treatment), and Visit 6 (Day 22 ±3, 15 minutes post treatment)..

The primary efficacy measure was ocular itching reported by the subject after a Conjunctival Allergen Challenge. The Ora Calibra scale ranges from 0 to 4: 0 is none, described as normal with no itching, and 4 is incapacitating itch. The outcome is described as a mean, with standard deviation as the dispersion measure, and its unit is units on a scale.

Itching is a symptom directly experienced by the participant, so a rating provides a way to quantify symptom intensity rather than relying only on a clinical sign. In this study, assessment after allergen challenge focuses the measurement on itching in the challenge model. The registry record specifies assessments at Visit 4b (Day 1, 16h post treatment), Visit 5b (Day 15 ±3, 8h post treatment), and Visit 6 (Day 22 ±3, 15 minutes post treatment). These are distinct assessment occasions and should not be treated as one result unless an analysis explicitly combines them.

As a general statistical point, a mean describes the average score, while a standard deviation describes variability among scores. Because the scale is bounded and ordered, a mean alone may not describe the full pattern of participant ratings. The registry record does not report the observed means, standard deviations, or distributions at the visits.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes the primary outcome as a mean of ocular itching scores and gives standard deviation as the measure of dispersion. It does not state which statistical test or model was used. The explanations below are general statistical context, not a claim about the analysis performed in this study.

What does a mean describe?

A mean combines individual scores into an average. It can make groups easier to compare, but it does not show whether most participants had similar scores or whether scores were widely spread. The standard deviation describes the spread of observations around the mean. A larger standard deviation indicates more variability in scores; it does not, by itself, show that the average is higher or lower.

The itching scale is bounded from 0 to 4 and uses ordered categories. As a general consideration, means can be useful summaries of such ratings, but the same mean can arise from different distributions of individual scores. Reporting distributions or additional summaries can help readers understand whether scores cluster near one end of the scale. Those summaries are not reported in the registry record.

What would a treatment contrast mean?

A treatment contrast would quantify the difference in average score between a bilastine regimen and vehicle at a specified assessment. Its direction depends on the subtraction convention used; the registry record does not report the contrasts or define a convention. The scale itself gives the clinical direction: lower scores correspond to less reported itching. A contrast needs to be read alongside its uncertainty and the time point it represents.

A confidence interval is a general way to express uncertainty around an estimated contrast. It describes a range of values compatible with the data and the statistical procedure, rather than proving that every value in the range is equally plausible. A narrow interval indicates greater precision than a wide interval. No confidence intervals are reported in the registry record, so the precision of the study's primary comparisons cannot be assessed from the posted results.

Why do the visits need attention?

The endpoint was assessed at Visit 4b, Visit 5b, and Visit 6, with different post-treatment intervals. If a participant contributes scores at more than one visit, those observations are related rather than independent. As a general statistical principle, an analysis of repeated measurements may need to account for within-participant correlation. Treating related observations as independent can misstate uncertainty. The registry record does not report how repeated assessments were handled, or whether the analyses treated each visit separately.

Repeated assessment can also create a multiplicity issue: when many comparisons are made, the chance of at least one apparently unusual result can increase. This is a general concern, not a claim that the study's results are false. The record lists 9 analyses, but does not describe which comparisons they represent or whether any adjustment or hierarchy was used. The actual statistical plan and its handling of multiplicity are not reported in the registry record.

What can randomization contribute?

In general, random assignment is intended to make treatment groups comparable on average with respect to measured and unmeasured characteristics. It does not guarantee that groups will be identical in a particular trial, especially in a modest-sized study. Baseline characteristics and the allocation procedures would help readers evaluate this aspect, but they are not reported in the registry record. The parallel design indicates that participants were assigned to regimen groups rather than a crossover sequence, but further design details are not given.

What does the sample-size approach tell readers?

The registry record describes a planning illustration based on an observed effect. It states a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. This describes assumptions for planning illustrations, not the trial's own design rationale. The record does not report the resulting planning sample sizes, nor does it report a sample-size justification used to design the trial. Planning illustrations are not observed power and do not reveal whether a study result is precise.

More broadly, a complete statistical interpretation would use the estimates, uncertainty intervals, analysis populations, missing-data handling, and prespecified analysis plan. These details are not reported in the registry record. Without them, the outcome description supports understanding what was measured, but not a reconstruction of the statistical analysis or its conclusions.

10. Multiplicity, Missing Data and Analysis Populations

The record identifies one primary outcome measure, ocular itching, but assesses it at Visit 4b, Visit 5b, and Visit 6. It also lists 9 analyses without describing the contrasts or showing their numerical results. The exact relationship between those analyses, the visits, and the four regimens is not reported in the registry record.

When multiple comparisons are conducted, the chance of finding at least one seemingly notable result can increase. Statistical plans may address this through a prespecified hierarchy or an adjustment to the inference procedure. Whether this trial used such an approach is not reported in the registry record. The record does not identify a primary time point among the listed assessments or explain how conclusions across visits were intended to be combined.

Missing-data handling is also not reported in the registry record. There is no description of how many participants had endpoint observations at each visit, how missing scores were treated, or whether any sensitivity analyses were conducted. The analysis population is not reported in the registry record, so it is not possible to determine whether results were based on all randomized participants, participants who received treatment, or another defined group.

These omissions limit assessment of the robustness and interpretability of the efficacy analyses. They do not show that data were missing or that multiplicity was mishandled; they mean that the registry record does not document those details.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures list 0 affected in the bilastine 0.2% group, with 30 at risk; 0 affected in the bilastine 0.4% group, with 30 at risk; 0 affected in the bilastine 0.6% group, with 31 at risk; and 0 affected in the bilastine 0% vehicle group, with 30 at risk. Deaths are listed as 0 for each group.

These counts mean that no serious adverse events or deaths are recorded for the listed groups in the registry results. A zero count is not proof of zero risk: it describes what was recorded during the study and does not establish that an event could never occur. The registry record does not report the serious-event definitions, the event-collection procedures, or the duration of safety follow-up.

Other adverse events are listed separately, with affected counts of 8, 3, 1, and 7 in the bilastine 0.2%, 0.4%, 0.6%, and 0% groups, respectively. Those counts should not be interpreted as serious adverse events. Details of the events and their severity are not reported in the registry record.

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

This study's registry record establishes the question and measurement approach: ocular itching after allergen challenge was assessed on a 0 to 4 scale at three stated visits, comparing three bilastine concentrations with vehicle. It also records a completed, randomized, parallel-group phase 2 study at a single center, with enrollment listed as 121.

The record does not report the primary outcome values or statistical comparisons. It therefore does not show whether itching scores differed between any bilastine regimen and vehicle, how large a difference might have been, or how precise an estimate was. No conclusion about benefit or lack of benefit can be drawn from the outcome description alone. The same limitation applies to judging whether results were consistent across visits or concentrations.

In general, a treatment comparison is most informative when it includes the estimated difference, an uncertainty interval, and a clear account of the analysis. A p-value, if reported, would address compatibility with a specified statistical null model; it would not by itself express the magnitude or practical importance of a difference. None of these efficacy results is reported in the registry record.

The safety counts offer a limited description: serious adverse events and deaths are recorded as 0 in each listed group. They do not establish the absence of all harms, and the record does not give enough information about ascertainment or follow-up to make broader safety claims. The other adverse event counts are separate from the serious-event counts and lack event-level detail.

Accordingly, the registry record is useful for identifying the study design, symptom scale, assessment schedule, and recorded safety counts. It is not sufficient to determine the efficacy results or to evaluate the full statistical analysis.

13. Why This Trial Matters Statistically

The trial raises statistical issues that are common in clinical research using symptom scales. Ocular itching is measured on a bounded 0 to 4 rating scale, and the registry describes the outcome using means and standard deviations. Understanding such summaries requires attention to both the average score and how participant ratings are distributed. A mean alone may not convey whether responses were concentrated or varied widely.

The three assessments occur at different visits and different post-treatment intervals. This makes the timing of each estimate important: a comparison at one visit answers a different question from a comparison at another. If measurements from the same participants are analyzed together, their relationship must also be considered when estimating uncertainty. The registry record does not report how these issues were addressed.

Multiplicity is another relevant consideration because the record lists 9 analyses while the endpoint is measured at three visits across four regimens. The precise comparisons and any plan for controlling or organizing multiple inferences are not reported. Readers cannot establish from the record whether the reported analyses were prespecified or how they were interpreted.

Finally, the record distinguishes the planned clinical question from the information available for evaluating it. It documents randomization, a vehicle comparator, the assessment scale, and serious adverse event counts, but it does not report the primary outcome estimates or their uncertainty. That distinction is important: knowing what a study set out to measure is not the same as knowing what its results show.

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 primary limitation for interpreting efficacy is that the registry record describes the ocular itching endpoint but does not report its observed results. Means, standard deviations, treatment contrasts, confidence intervals, and p-values are not reported in the registry record. This prevents assessment of effect direction, magnitude, and precision.

The endpoint is assessed at three visits, but the record does not identify one primary assessment time among them or explain how the visit-specific results were analyzed. Although 9 analyses are listed, their content and relationship to the visits and regimens are not reported. Multiplicity procedures are not reported in the registry record.

Further limitations include the absence of reported participant characteristics, group assignment counts, baseline outcome values, analysis populations, and missing-data procedures. Details of randomization and allocation concealment are also not reported. The official title calls the study double-masked, while the registry classification lists masking as triple; the record does not explain the difference.

The safety information is limited to counts. Event definitions, collection procedures, follow-up duration, and details of the other adverse events are not reported in the registry record. These gaps restrict interpretation of both safety and efficacy, but do not establish that any particular method or procedure was absent from the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Single-Center, Phase 2 Study Evaluating Bilastine Ophthalmic Solution in the CAC® Model — NCT03231969.
• Registry record last updated 2023-03-16; status last verified 2021-10.
• Results first posted 2021-11-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

This completed, single-center, randomized, parallel-group phase 2 study evaluated bilastine ophthalmic solution at 0.2%, 0.4%, and 0.6% against vehicle in allergic conjunctivitis using the Conjunctival Allergen Challenge model. Enrollment is listed as 121. The official title describes the study as double-masked; the registry classification lists masking as triple.

The primary measure was subject-reported ocular itching on a 0 to 4 Ora Calibra scale, assessed after challenge at Visit 4b, Visit 5b, and Visit 6. The registry record does not report numerical efficacy results, analysis populations, missing-data handling, or multiplicity procedures. Serious adverse events and deaths are listed as 0 in each regimen group; other adverse event counts are also recorded, without event details.