Evaluation of Brimonidine Tartrate/Ketotifen Fumarate Combination for the Treatment of Allergic Conjunctivitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Brimonidine Tartrate/Ketotifen Fumarate Combination for the Treatment of Allergic Conjunctivitis (NCT05579730), a randomized phase 3 study. The primary outcome is Ocular Itching.

2. Clinical Question

The trial was designed to assess ocular itching after allergen challenge among people with allergic conjunctivitis. It compared an ophthalmic solution combining brimonidine tartrate 0.025% and ketotifen fumarate 0.035% with each component alone and with vehicle. The study used a conjunctival allergen challenge model, in which the endpoint was assessed following challenge at specified post-instillation times.

The central statistical question is whether the mean ocular itching scores recorded for the combination differ from those recorded for the component treatments and vehicle at the stated assessments. The registry record identifies the outcome and its assessment schedule, but it does not provide the group means, measures of uncertainty, between-group comparisons, or test results. Accordingly, the record does not establish the size or direction of any observed differences, or how precisely those differences were estimated.

The record reports 188 enrolled participants and four treatment groups. It does not report the number included in the primary outcome analysis, the number contributing data at each assessment, or whether participants were excluded from any analysis. It also does not report the population to which the primary analysis was applied. These missing details matter because the interpretation of a comparison depends not only on which treatments were assigned, but also on which participants and observations were included.

3. Trial Design

The registry identifies this as a phase 3, randomized, double-masked, parallel-group trial. Enrollment was 188, and the study is listed as completed. The registry lists a start date of 2022-10-12 and a primary completion date of 2023-07-22. Bausch & Lomb Incorporated is named as the sponsor.

Participants were assigned among four ophthalmic solution groups: the combination of brimonidine tartrate 0.025% and ketotifen fumarate 0.035%, ketotifen fumarate 0.035% alone, brimonidine tartrate 0.025% alone, or vehicle. Randomization means assignment was made using a randomized process, which is intended to support fair comparisons between groups. The record does not report the allocation ratio, the randomization procedure, or whether any stratification was used. Double masking indicates that the study was described as double-masked, but the identities of the masked parties and the practical masking procedures are not reported in the registry record.

The parallel design means participants were assigned to a treatment group rather than being described as crossing among treatments. The trial used a conjunctival allergen challenge model, as stated in its official title. That context is important for reading the endpoint: the outcome is an itching score following challenge at specified times after study medication, rather than a broad measure of symptoms collected without that challenge context.

The record describes assessments at Visit 4b on day 1, eight hours after instillation, and Visit 5 on day 15, fifteen minutes after instillation. It does not report the detailed visit schedule, the duration of treatment between assessments, adherence, participant flow, or the number analyzed in each group. The registry lists two outcome measures, but the available record does not describe the other outcome measure in the registry record for this analysis. Statistical analysis details, including model choice and adjustment procedures, are not reported in the registry record.

Enrollment is a planned or recorded count of people entering the study, not necessarily the number contributing complete outcome data. The record does not supply enough information to determine whether all enrolled participants were randomized, received assigned treatment, or had usable primary outcome measurements. Those distinctions are relevant when interpreting randomized clinical trial results.

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 Assessed at Visit 4b on day 1 (duration of action CAC at 8 hours post-instillation of study medication) and Visit 5 on day 15 (onset of action CAC at 15 minutes post-instillation of study medication)..

The primary outcome is ocular itching, measured as a score on a scale. Participants assessed itching after conjunctival allergen challenge, and the score was the average of the subject’s two eyes. The scale ran from 0-4 units and allowed half-unit increments. Assessments were made at 3 (±1), 5 (±1), and 7 (±1) minutes after challenge.

The registry describes two assessment settings: Visit 4b on day 1, for duration of action at eight hours after study medication was instilled, and Visit 5 on day 15, for onset of action at fifteen minutes after instillation. This schedule means the endpoint concerns itching at multiple post-challenge assessment times and in distinct medication-timing contexts. The record does not provide scores for any of these assessments, nor does it identify a single summary contrast that combines them.

A symptom score is useful because it turns a subjective experience into a structured outcome that can be compared between randomized groups. Averaging the two eyes gives a participant-level score as described in the record; it does not make the outcome an objective laboratory measurement. As a continuous outcome, the reported summary type is a mean, with standard error as the dispersion measure. A mean describes the group’s average score, while a standard error describes uncertainty in estimating that mean. Neither the means nor their standard errors are reported in the registry record, so the magnitude and precision of group differences cannot be assessed.

The registry says the score was assessed at the listed challenge-related minutes. It does not report which time point, if any, was designated as the principal contrast for inference, or how results across these assessments were handled statistically.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-masked, parallel-group trial. Random assignment is intended to make treatment groups comparable on average with respect to both measured and unmeasured characteristics. It does not guarantee that groups will be identical, especially in a finite study. The record does not describe the randomization sequence, allocation concealment, or group allocation ratio, so those procedural details are not available for assessment.

What does a mean and standard error describe?

The primary outcome is a continuous itching score, and the registry identifies the mean as the summary parameter and standard error as the dispersion measure. A mean summarizes the central level of scores in a group. The standard error reflects the uncertainty of the estimated mean; it is not the same as the spread of individual participants’ scores. The registry does not report the group means or standard errors, so these summaries cannot be interpreted for this trial. Nor does the record provide an estimated difference between groups, which would be needed to describe the direction and magnitude of a comparison.

In general, a treatment contrast is an estimate comparing an outcome between groups. For a continuous endpoint, such a contrast might be expressed as a difference in mean scores, depending on the prespecified analysis. That is a general description, not a claim about the analysis used in this trial. The registry does not report the statistical model, the form of the treatment contrast, covariates, or adjustment for repeated measurements.

Why do the assessment times matter?

The primary endpoint description includes itching scores at 3 (±1), 5 (±1), and 7 (±1) minutes after challenge. The time of assessment relative to study medication also varies: the record describes a duration-of-action assessment at Visit 4b on day 1, eight hours after instillation, and an onset-of-action assessment at Visit 5 on day 15, fifteen minutes after instillation. Repeated assessments from the same participant are related rather than independent observations. In general, an analysis of repeated measurements needs to account for that dependence or define a particular assessment as the main comparison. Which approach was used, if any, is not reported in the registry record.

The existence of several assessment times also raises a multiplicity question. In general, making many statistical comparisons can increase the chance of finding an apparently unusual result even when no true group difference exists. Prespecified testing strategies or multiplicity adjustments can address that issue, but the registry record does not report whether either was used. The record also does not state whether the several within-challenge minute scores were analyzed separately, combined, or summarized in another way.

How should uncertainty be understood?

In general, a confidence interval pairs an estimate with a range expressing sampling uncertainty under the specified method. A narrow interval indicates greater precision than a wide interval, all else equal. A p-value is a measure calculated under a null hypothesis and model assumptions; it is not an effect-size measure and does not tell readers whether a difference is meaningful. No confidence intervals or p-values for the primary outcome are reported in the registry record. As a result, precision and statistical compatibility with a null comparison cannot be described for ocular itching.

The summary-statistic type does not by itself identify an analysis model. For example, a mean and standard error can be presented alongside results from different models or from unadjusted summaries. The record does not say whether the primary analysis was adjusted, whether baseline or other covariates were included, or how data from the two eyes were handled beyond the stated average of each subject’s eyes. Any more specific account of the analysis would be speculation.

What do the planning illustrations represent?

Planning illustrations use a two-sided significance level of 0.05, equal allocation between the two arms being compared, and a normal approximation. Their target effect is stated as a fraction of the observed effect. Such values describe hypothetical sample sizes for planning under those assumptions, not the study’s observed statistical power. Sample-size estimates based on an observed effect are sensitive to that effect estimate, and they do not replace the trial’s own prospective design rationale. The study’s original sample-size justification is not reported in the registry record. Numerical planning estimates and the effect estimates used for them are not reported in the registry record analyzed.

In general, power is a design property tied to a specified effect, variability, analysis method, significance level, and sample size. It is not an after-the-fact probability that a reported finding is true. A planning illustration should therefore be read as conditional on its assumptions, not as proof that the study was adequately powered or that a particular result is reliable. No statement about observed power can be made from the registry record.

Finally, the record reports no statistical analyses for the primary outcome. It therefore does not permit confirmation of model assumptions, standard error calculations, handling of repeated observations, or robustness checks. These are important features of a statistical analysis, but their use or results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is assessed at multiple post-challenge minutes and in two medication-timing contexts. The record does not describe how those assessments were prioritized or whether any adjustment was made for multiple testing. It also does not report which comparisons among the combination, component treatments, and vehicle were designated as primary. Without a stated testing strategy, the error rate associated with a collection of comparisons cannot be evaluated.

Missing-data procedures are not reported in the registry record. The record does not provide the number of participants with an ocular itching score at each visit or assessment, the reasons observations might be missing, or the method used to handle incomplete outcomes. It does not report whether any imputation, sensitivity analysis, or other missing-data approach was used. The enrollment count alone cannot establish how many observations contributed to the endpoint analyses.

Analysis populations are also not reported. The registry record does not specify whether analyses included all randomized participants, only those who received treatment, only participants with outcome measurements, or another defined group. It does not describe protocol deviations or exclusions. These details can affect the interpretation of a randomized comparison, particularly if the analyzed participants differ from those initially assigned.

Interim analyses and stopping rules are not reported in the registry record. Their absence from the record should not be treated as evidence that none were planned or conducted; the record does not establish either way. Overall, the registry does not provide enough information to assess multiplicity control, missing-data handling, or the populations used for analysis.

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 registry lists serious adverse event counts and other adverse event counts separately for each treatment group, along with the number at risk for each category. For the combination group, the serious adverse event count is 0 and the other adverse event count is 3, with 47 at risk. For ketotifen fumarate, the corresponding figures are 0 and 6, with 48 at risk. For brimonidine tartrate, they are 0 and 6, with 47 at risk. For vehicle, they are 0 and 4, with 46 at risk. The deaths count is 0 in each group.

These are the counts listed in the registry record, not estimates of comparative risk. No percentages or between-group safety analyses are reported, and none should be inferred from the counts alone. The record does not provide event descriptions for the other adverse events or clarify their severity, timing, relatedness to treatment, or whether participants could have experienced multiple events. No serious adverse event terms are listed.

Zero serious events recorded for a group does not establish that serious events are impossible or that groups have equivalent safety. The counts are limited to the information recorded in the registry, and the record does not supply further follow-up or adjudication details. These figures should be read as descriptive counts, not as a complete characterization of safety.

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

This trial record describes a randomized, double-masked comparison of a brimonidine tartrate/ketotifen fumarate combination with its two components and vehicle in an allergic conjunctivitis challenge model. It identifies ocular itching as the primary outcome and specifies the score scale and assessment schedule. Those design details indicate what the trial set out to measure, but they do not tell readers what the measured outcomes were.

The registry record does not report numerical primary outcome results, group comparisons, or inferential statistics. It therefore cannot establish whether the combination group had higher or lower itching scores than any comparator, whether differences were estimated precisely, or whether any observed difference was statistically distinguishable from chance under a particular analysis. It also cannot show whether any difference was large enough to matter to participants.

The recorded adverse-event counts provide limited descriptive safety information. They do not support a complete comparison of harms because the record does not give event-level details, comparative analyses, or further information about follow-up and attribution. The counts of zero serious adverse events in the groups should not be interpreted as evidence that risk is absent or identical.

More generally, a trial’s design and its results are distinct. Randomization and masking can support credible comparisons when appropriately implemented and analyzed, but they do not substitute for outcome estimates. To interpret the primary question, readers would need the numerical scores or contrasts, uncertainty measures, analysis populations, and methods used to handle repeated assessments and missing data. Those items are not reported in the registry record.

The registry describes a completed phase 3 study with enrollment of 188, but completion and enrollment alone do not indicate the direction or precision of a treatment effect. The available information supports a description of the trial’s setup and recorded adverse-event counts. It does not support a conclusion that one treatment is superior, equivalent, or ineffective.

13. Why This Trial Matters Statistically

The trial illustrates why a clear endpoint definition and a reported analysis are both necessary for statistical interpretation. Ocular itching is recorded using a defined scale, averaged across each subject’s two eyes, and assessed after challenge at specified times. This gives readers a concrete description of the outcome, but without the group-level results it remains impossible to quantify what the comparison showed.

The design includes a combination treatment, each of its individual components, and vehicle. That structure can address more than one scientific contrast: the combination can be compared with the components and with vehicle. Multiple treatment groups and assessment times make it especially important to distinguish prespecified primary comparisons from additional analyses and to understand any multiplicity strategy. The registry record does not report those details or the statistical analyses.

The record also demonstrates the difference between descriptive safety counts and a comparative safety analysis. Counts of serious and other adverse events are listed for each group, but the record does not provide event-level detail or comparative estimates. These counts are informative as a registry entry, yet they cannot answer every question about relative safety or precision.

Finally, enrollment should not be confused with analyzed sample size, and planning illustrations should not be confused with observed evidence. The record reports enrollment of 188, while the analysis population and endpoint-specific participant counts are not reported. The planning assumptions describe conditional sample-size illustrations, not observed power. Together, these points emphasize that transparent outcome reporting, analysis methods, missing-data information, and participant flow are needed to evaluate how strongly a clinical trial supports its statistical conclusions.

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 principal limitation for interpreting this trial from the registry record is the absence of numerical primary outcome results. No means, standard errors, contrasts, confidence intervals, or p-values for ocular itching are reported. Consequently, effect direction, magnitude, and precision cannot be assessed. The record also lists no statistical analyses, so the method used to compare treatment groups is not available.

The outcome is described at multiple assessment times after challenge and at two medication-timing visits. The record does not state which time point or contrast was the primary inferential target, or how repeated scores were handled. The way multiple treatment comparisons and assessment times were addressed is not reported. This limits the ability to understand the intended interpretation of the endpoint.

Several design and analysis details that would inform appraisal are not reported in the registry record, including eligibility criteria, allocation ratio, randomization procedures, analysis populations, participant flow, endpoint-specific sample sizes, and missing-data methods. The record does not provide the original sample-size justification, an interim-analysis plan, or details of statistical model assumptions. These omissions should be treated as unknowns, not as evidence that a particular method or procedure was or was not used.

The adverse-event information is limited to group counts for serious and other events, at-risk counts, and deaths. Event descriptions and comparative safety analyses are not reported. Thus, those figures provide only a narrow descriptive view of safety and cannot resolve questions about event type, timing, attribution, or relative risk.

Finally, the conjunctival allergen challenge model defines the context in which itching was assessed. The registry record does not provide enough information to characterize how the study population or challenge assessments relate to other settings. The findings’ broader applicability cannot be determined from the record, particularly because the numerical outcome results themselves are not reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of Brimonidine Tartrate/Ketotifen Fumarate Combination for the Treatment of Allergic Conjunctivitis — NCT05579730.
• Registry record last updated 2025-02-14; status last verified 2025-01.
• Results first posted 2025-02-14.
• 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

NCT05579730 is listed as a completed phase 3, randomized, double-masked, parallel-group trial sponsored by Bausch & Lomb Incorporated. The registry reports 188 enrolled participants and study dates from 2022-10-12 to primary completion on 2023-07-22. The trial evaluated brimonidine tartrate 0.025%/ketotifen fumarate 0.035% ophthalmic solution against ketotifen fumarate 0.035%, brimonidine tartrate 0.025%, and vehicle in an allergic conjunctivitis conjunctival allergen challenge model.

The primary outcome was ocular itching, scored from 0-4 with half-unit increments and averaged across each subject’s two eyes. Assessments followed challenge at 3 (±1), 5 (±1), and 7 (±1) minutes, with visits described for eight hours and fifteen minutes after instillation. Numerical primary outcome results and statistical analyses are not reported in the registry record. The record lists zero serious adverse events and zero deaths in each group, alongside other adverse-event counts of 3, 6, 6, and 4 for the combination, ketotifen fumarate, brimonidine tartrate, and vehicle groups, respectively.