Efficacy and Safety of AL-4943A Ophthalmic Solution in Patients With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of AL-4943A Ophthalmic Solution in Patients With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model (NCT01479374), a randomized phase 3 study. The primary outcome is Mean Ocular Itching at Onset of Action.

2. Clinical Question

The study asked whether AL-4943A could be evaluated for safety and efficacy for ocular itching associated with allergic conjunctivitis in a controlled allergen-challenge setting. CAC is the model specified in the study title and description; the result therefore concerns itching assessed following that challenge, not every possible setting in which allergic conjunctivitis may occur.

The intervention and comparator arms allow a study to make comparisons against vehicle and an active control, but the registry record does not identify a particular pairwise contrast as the one primary comparison. It also does not give arm-level primary endpoint means, a difference between arms, confidence intervals, or a p-value. Consequently, the clinical question can be described, but a numerical answer cannot be recovered from the posted primary outcome information.

3. Trial Design

This was a phase 3, randomized, parallel-group study of AL-4943A ophthalmic solution in patients with allergic conjunctivitis. The registry lists the study as completed and records enrollment of 397. It identifies Alcon Research as the sponsor. The recorded study start is 2012-01 and primary completion is 2012-03.

Three interventions are described: AL-4943A, its vehicle, and olopatadine hydrochloride ophthalmic solution, 0.2%, identified as Pataday in the arm descriptions. Each arm description states that one drop was given to each eye on 3 nonconsecutive days. The official title identifies AL-4943A as a 0.77% solution and describes the study as multi-center, randomized, double-masked, vehicle and active controlled. The registry's masking field lists triple masking. These are both features of the record; further detail resolving the difference in masking terminology is not reported in the registry record.

The primary endpoint was assessed on Day 21 of treatment, after a treatment efficacy CAC. The description says the challenge was performed 27 minutes after drop instillation. It also specifies assessment of itching at 3, 5, and 7 minute timepoints following CAC. The registry describes the measure as an average of itching scores over both eyes, reported as a mean on a 0-4 scale.

The reported enrollment and the group counts in the adverse-event record are different types of information. The record does not explain the relationship between them, and the adverse-event counts should not be treated as a substitute for the enrollment figure. A protocol, detailed allocation counts, and a full 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: Of the 397 enrolled, 195 subjects did not qualify for treatment and were exited without exposure to product. Participant flow and baseline characteristics are presented for the 202 subjects qualifying for treatment and randomized 1:1:1 to receive AL-4943A, Vehicle, or Pataday.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT). The analysis population included all randomized patients who received treatment and had post CAC data.

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 Mean Ocular Itching at Onset of Action, measured over 3, 5, and 7 minute timepoints, post-CAC on Day 21 of receiving treatment.

The primary endpoint was mean ocular itching at onset of action. Participants rated itching on a 0-4 scale, where 0 means none and 4 means incapacitating itch. The score was averaged over both eyes. Assessments occurred at the 3, 5, and 7 minute timepoints after CAC on Day 21 of treatment. The treatment efficacy challenge was performed 27 minutes after drop instillation.

Itching is the symptom named in the study purpose, so a patient-rated itching score directly represents the symptom the trial set out to assess. Averaging scores across the eyes yields one summarized measure per participant at each stated assessment time. The score is bounded and ordered: higher values correspond to more severe reported itching. Treating the average as a continuous measure allows a mean to describe the group, although that summary alone does not show the full distribution of individual ratings.

“Onset of action” refers to the early post-challenge assessment period defined in the endpoint description. It should not be read as a measure of duration or as evidence about effects outside the CAC setting. Other listed outcomes concern redness and itching at additional timepoints, but the registry record does not give their numerical results.

No arm-level means, dispersion estimates, treatment contrast, confidence interval, or significance test for this primary endpoint are reported in the registry record. The scale and assessment schedule are described, but the magnitude and precision of any between-group difference cannot be assessed from the primary outcome entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous in the registry’s outcome classification and is described as a mean with standard deviation. It comes from a bounded patient rating: 0 means no itching and 4 means incapacitating itch. The score averages the two eyes, with assessments at the 3, 5, and 7 minute timepoints after CAC. These details define the outcome, but they do not reveal which statistical model was used to compare groups.

What does a mean describe?

In general, a mean is a measure of the group’s average score. It is useful for describing the central level of a continuous outcome and for expressing an average contrast between groups when one is specified. A mean does not show every participant’s response. Two groups can have similar means but different distributions, and a mean alone does not show how many people experienced a particular score.

The standard deviation describes spread among observed scores around a group mean. It is not the same as the uncertainty in the mean or the uncertainty in a between-group comparison. In general, a confidence interval for an estimated mean or contrast communicates that inferential uncertainty. The registry record provides neither the endpoint’s standard deviations nor confidence intervals for a primary contrast.

How should the repeated timepoints be understood?

The primary outcome description includes assessments at 3, 5, and 7 minutes after CAC. These are multiple measurements within the endpoint schedule, rather than a single timepoint result. In general, repeated measurements from the same participant are related; they should not automatically be treated as independent observations. An analysis may summarize timepoints separately, define a combined summary, or model the repeated pattern. Which approach was used is not reported in the registry record.

The record notes that the primary outcome has several categories or timepoints and was not reduced to one comparison. Accordingly, the listed timing should not be collapsed into an unreported average or selected timepoint. The registry does not supply estimates for each timepoint or a rule for choosing among them.

What does randomization contribute?

In general, random allocation is intended to make study groups comparable at baseline, on average, so that differences in outcomes can be interpreted as comparisons between assigned groups under the study conditions. Randomization does not ensure that every measured or unmeasured characteristic is balanced in a particular trial. Details of the allocation sequence and concealment are not reported in the registry record.

The registry describes the study as randomized and parallel-group. The official title calls it double-masked, while the registry masking field says triple. Masking is generally intended to reduce the influence of expectations or knowledge of assigned treatment on care, reporting, or assessment. The record does not explain who was masked or how the two masking descriptions relate.

What can be concluded from significance testing?

In general, a p-value evaluates how compatible the observed data are with a specified null hypothesis under a statistical model. It does not state the probability that a treatment effect is true, and it does not convey the size or clinical importance of an effect. A p-value is not reported for a primary comparison in this record. No hypothesis, test statistic, or analysis model for such a comparison is reported either.

In general, confidence intervals are important alongside significance tests because they show a range of effect sizes compatible with the data and analysis assumptions. Without a contrast estimate and interval, readers cannot judge whether the available data are consistent with a small effect, a larger effect, or effects in different directions. This limitation is about the registry record’s reported results; it is not evidence that no analysis was performed outside the record.

What do planning calculations mean?

In general, a sample-size calculation asks how many participants per arm would be needed under specified assumptions to detect a chosen effect with a chosen power and significance level. The described planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are framed around fractions of an observed effect. Such illustrations are hypothetical planning aids, not the trial’s enrollment rationale, not the actual allocation, and not observed power. The registry does not report the trial’s own sample-size justification or statistical plan. No additional planning result can be inferred from the primary endpoint entry.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is recorded across the 3, 5, and 7 minute timepoints after CAC, and the registry explicitly notes that it has several categories or timepoints and was not reduced to one comparison. A trial with multiple timepoints or multiple comparisons raises a multiplicity issue: in general, the chance of at least one false-positive finding can increase when many hypotheses are tested without an appropriate strategy. A prespecified hierarchy, adjustment, or other analysis plan can address this concern, but the strategy used is not reported in the registry record.

The registry lists additional secondary outcomes for redness and itching at other assessment times. It does not provide their numerical results or describe how they were incorporated into an overall testing strategy. The number of outcome measures is listed as 7, but that count does not itself explain which tests were conducted, whether they were prespecified, or how multiplicity was handled.

The described intent-to-treat population includes randomized patients who received treatment and had post-CAC data. The number of participants included in the primary analysis, the amount of missing endpoint data, and the reasons for missingness are not reported in the registry record. Rules for imputation, exclusion, or sensitivity analyses are also not reported. In general, missingness matters because an analysis restricted to participants with observed data can be biased if the chance of having data is related to outcome or treatment. The record does not provide enough information to assess that possibility.

The outcome registry lists 0 analyses. This means the registry entry does not present a primary comparison to interpret; it does not establish whether analyses were conducted elsewhere. The statistical analysis plan, handling of repeated measurements, and prespecified method for addressing multiple comparisons are not reported in 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.

The registry reports serious adverse-event counts of 0 for AL-4943A, 0 for Vehicle, and 0 for Pataday. For the other adverse-event category, it also reports 0 for each group. The corresponding participants at risk are recorded as 66 for AL-4943A, 68 for Vehicle, and 68 for Pataday. These are the figures listed in the registry’s adverse-event entry; they should be read as recorded event counts alongside the listed at-risk counts.

A zero count in this summary means that no event in the specified category was reported for the listed group in this record. It does not establish that no adverse experiences of any kind occurred, that all possible harms were assessed, or that the treatments are equivalent in safety. The record does not include a list of common non-serious events or additional detail on event ascertainment in this entry.

Deaths are marked as not reported in the registry record. That is different from a reported zero death count, so no conclusion about deaths should be drawn from this entry. The record also does not report exposure-adjusted rates or confidence intervals for adverse-event comparisons. These summaries describe what is entered in the registry and do not quantify uncertainty around differences between groups.

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

The registry record is informative about the study question and its structure. It describes a randomized phase 3, parallel-group CAC study in allergic conjunctivitis, with AL-4943A, vehicle, and olopatadine arms. It specifies a patient-rated itching scale, the early post-challenge assessment times, and the intent-to-treat population definition. Those details allow readers to understand what the primary outcome was meant to capture.

However, the record does not present the numerical primary endpoint results as a single comparison. There are no posted arm means, no treatment-effect estimate, and no confidence interval or p-value for that comparison. Thus, the registry entry does not quantify how much the groups differed, how precise any difference was, or whether the data were compatible with a range of effects. It cannot support a conclusion about the magnitude or statistical evidence of an effect on the basis of the primary endpoint.

The same distinction applies to safety. The record lists zero serious and zero other adverse events in the specified groups, but deaths are not reported, and the entry is not a comprehensive description of every safety measure or its uncertainty. A registry summary is not equivalent to a full clinical study report.

In general, trial results should be interpreted in the context of outcome definitions, analysis methods, missing data, and prespecified comparisons. Here, the multiplicity strategy, model for repeated assessments, and missing-data methods are not reported in the registry record. That limits the ability to assess the robustness of any result even if a numerical finding is available elsewhere.

The trial’s setting also matters: the endpoint is itching after a conjunctival allergen challenge on Day 21, not a measure of every symptom, duration, or real-world circumstance. The record establishes the trial’s intended assessment but does not provide enough result information to infer a treatment effect or its broader relevance.

13. Why This Trial Matters Statistically

This study illustrates why a trial’s question and its results are separate pieces of evidence. The registry gives a relatively specific description of the primary outcome: a patient-rated itching score averaged over both eyes, measured at several early timepoints following CAC. That specificity helps readers distinguish the endpoint from the listed redness outcomes and from later itching assessments.

At the same time, the record does not reduce the multiple primary assessment times to one reported comparison, and it provides no numerical primary outcome results. Without an estimate and uncertainty interval, readers cannot judge the scale or precision of any group difference. A trial can have a clear design and outcome definition while still leaving the registry reader without the central quantitative result needed for statistical interpretation.

The entry also highlights the importance of transparent analysis reporting. Repeated measurements can be handled in different ways, and a study with multiple outcomes and timepoints needs a clear account of its prespecified comparisons and multiplicity strategy. Those methods are not reported. Likewise, the intent-to-treat definition depends on treatment receipt and post-CAC data, but the number analyzed and missing-data handling are absent.

Finally, summary safety counts need careful boundaries. The listed zeros describe specific adverse-event categories and groups; they do not provide a complete safety profile or uncertainty assessment, and the death counts are not reported. Taken together, the record offers useful design and measurement details while demonstrating that statistical value depends not only on a trial’s planned question but also on complete, interpretable reporting of estimates, uncertainty, and analysis decisions.

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 most important limitation for interpreting efficacy is that the registry record does not report a numerical result for the primary endpoint. It gives neither means by arm nor a contrast, confidence interval, or p-value. The record also says the primary outcome involves several categories or timepoints and was not reduced to one comparison. The direction, size, and precision of a primary effect therefore cannot be evaluated from this entry.

The endpoint is tied to a specific CAC assessment schedule on Day 21, with itching recorded at the 3, 5, and 7 minute timepoints after challenge. The record does not give results for each timepoint or explain how they were analyzed together. Results from this setting, even if reported elsewhere, would address the challenge-based measure described rather than every aspect of allergic conjunctivitis.

Important analysis details are absent. The registry does not report a statistical analysis plan, the method for repeated measures, multiplicity adjustment, sample-size justification, or handling of missing endpoint data. It defines the intent-to-treat population as randomized patients who received treatment and had post-CAC data, but does not state how many were analyzed or how many had missing data.

The registry gives both a double-masked description in the official title and triple masking in its masking field; it does not explain the terminology. It also reports an enrollment figure separately from the at-risk counts in the adverse-event entry without explaining their relationship. These record-level details should not be reconciled by assumption. The safety entry is limited to the recorded categories, and death counts are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of AL-4943A Ophthalmic Solution in Patients With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model — NCT01479374.
• Registry record last updated 2013-06-04; status last verified 2013-05.
• Results first posted 2013-05-23.
• 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

NCT01479374 is a completed phase 3 randomized, parallel-group study of AL-4943A ophthalmic solution in patients with allergic conjunctivitis, using the CAC model. The registry records enrollment of 397 and lists AL-4943A, vehicle, and olopatadine hydrochloride ophthalmic solution, 0.2% as study interventions. The primary endpoint was mean ocular itching on a 0-4 scale at the 3, 5, and 7 minute timepoints following CAC on Day 21.

The registry defines the primary analysis population as randomized patients who received treatment and had post-CAC data. It does not report a single primary comparison, endpoint estimates, or their uncertainty. The record lists zero serious and zero other adverse events in each group; deaths are not reported in the registry record. Statistical details for multiplicity, repeated measures, and missing data are also not reported.