Efficacy of AC-170 for the Treatment of Allergic Conjunctivitis in the Conjunctival Allergen Challenge (CAC) Model: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of AC-170 for the Treatment of Allergic Conjunctivitis in the Conjunctival Allergen Challenge (CAC) Model (NCT01332188), a randomized phase 2, phase 3 study. The primary outcome is Ocular Itching at Duration of Action (16 Hours Post-dose).

2. Clinical Question

The study asked whether different concentrations of AC-170, compared with vehicle, affected signs and symptoms of allergic conjunctivitis in a conjunctival allergen challenge (CAC) model. Its primary question focused on ocular itching at the duration-of-action assessment: a CAC was conducted 16 hours after drop instillation, and participants rated itching at 3, 5, and 7 minutes after the challenge. The registry identifies the primary analysis population as the Intent to Treat population and describes the outcome as the mean of the itching scores averaged over both eyes.

The question is specific to symptoms elicited under the CAC procedure and to the stated post-instillation assessment. It is not a question about symptoms in everyday settings or about outcomes outside those recorded for the study. Although the registry lists secondary outcomes involving redness, chemosis, and other assessment times, numerical findings for those outcomes are also not included in the record. Consequently, the study question can be described, but the posted information does not establish the direction, size, or precision of any treatment-group difference.

3. Trial Design

The registry describes a randomized, double-masked, parallel-group study at a single center, with vehicle control. Its listed phase is Phase 2 and Phase 3, and its status is completed. The record gives enrollment as 101 and identifies allergic conjunctivitis as the condition. The listed study period runs from 2011-04 to primary completion in 2011-06. The sponsor is Aciex Therapeutics, Inc.

Four intervention groups are listed: AC-170 0.05%, AC-170 0.1%, AC-170 0.24%, and AC-170 0%. The last is the vehicle comparator. The arm-description fields contain no further descriptions. Randomized allocation means participants were assigned among the listed groups, but the sequence-generation procedure, allocation-concealment details, and group-specific enrolled totals are not reported in the registry record. Double masking is stated; which individuals were masked and how masking was maintained are not reported.

The primary endpoint was measured in an allergen-challenge setting. A treatment efficacy CAC was performed 16 hours after drop instillation. Participants assessed ocular itching on a scale from 0, meaning none, to 4, meaning severe, at 3, 5, and 7 minutes after CAC. The reported endpoint definition specifies an average itching score over both eyes. The primary outcome population is listed as Intent to Treat.

The registry lists 37 outcome measures. Secondary outcomes include ciliary redness, episcleral redness, and chemosis at specified onset or duration assessments. The record does not describe the timing or procedure for every listed outcome in detail. It also does not give a full protocol, a statistical analysis plan, or numerical primary-outcome results. Thus, the design features and intended outcome can be outlined, while important operational and analytical details remain unavailable 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: 101 subjects were enrolled, 7 subjects discontinued, and 94 subjects completed the study. The 101 subjects that met all inclusion criteria and none of the exclusion criteria were randomized to receive AC-170 0.05%, AC-170 0.1%, AC-170 0.24% or AC-170 0%. Note: All solutions were "early formulations" and not the final to-be-marketed formulation.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT)

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 at Duration of Action (16 Hours Post-dose), measured over 3, 5, 7 minutes post-CAC.

The primary endpoint is ocular itching at the duration-of-action assessment, described as taking place 16 hours after drop instillation. Participants rated itching after the treatment efficacy CAC at 3, 5, and 7 minutes. The registry defines the scale from 0, none, to 4, severe, and states that the average score over both eyes was analyzed. The outcome is characterized as a continuous measure summarized by a mean and standard deviation.

Itching is a symptom reported by the participant, so it captures a subjective experience rather than an examiner-rated sign. In general, a prespecified symptom measure can provide a focused way to compare groups under a common assessment procedure. The CAC model supplies a controlled allergen-challenge context for eliciting and assessing symptoms; the registry’s stated objective is to evaluate prevention of signs and symptoms in that model. The endpoint’s timing makes it relevant to the study’s duration-of-action question, but it does not by itself establish how symptoms behave at other times or in settings outside the challenge.

The definition clarifies the scoring range, assessment timing, and two-eye averaging, but does not give group means, standard deviations, treatment contrasts, confidence intervals, or p-values. Those numerical results are not reported in the registry record. Without them, the endpoint can be interpreted as the planned measure, but the magnitude and precision of any observed difference cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry gives several elements needed to understand the intended statistical question, but it does not provide the analysis results or a full statistical plan. The distinctions below separate what the record states from general explanations of the statistical ideas involved.

What does a mean represent for this endpoint?

The primary outcome is described as a mean of a continuous measure. Each participant rated ocular itching using a scale from 0, none, to 4, severe. The registry says the average score over both eyes was analyzed, with assessments at 3, 5, and 7 minutes after CAC. A group mean would summarize the average score among the participants included in that group’s analysis. It would not show every participant’s response or how responses were distributed. The registry identifies standard deviation as the measure of dispersion, but no group means or standard deviations are reported in the registry record.

In general, a standard deviation describes how spread out individual observations are around their mean. Greater spread means participants’ values are more dispersed; it does not by itself indicate a larger or smaller average treatment effect. Both the mean and the dispersion would be useful for describing this endpoint, but neither can be interpreted comparatively without the corresponding reported values.

What can the randomized design contribute?

The design is labeled randomized, double-masked, and parallel-group. In general, random assignment aims to make treatment groups comparable with respect to measured and unmeasured characteristics, on average. A parallel-group design assigns participants to a group and compares outcomes between groups. Masking can help limit the influence of treatment expectations on participant ratings or study assessments. These are general design principles, not a guarantee that bias was absent in this study. The procedure used to generate assignments, conceal allocation, and preserve masking is not reported in the registry record.

The registry names the primary outcome population as Intent to Treat. In general, an Intent to Treat analysis seeks to retain participants in their assigned groups, regardless of whether they fully followed the assigned treatment. The exact implementation can vary, especially when outcome values are missing or participants do not complete assessments. The registry does not report the handling of missing observations, deviations from assigned treatment, or the specific participant set used in any numerical analysis.

How should uncertainty be assessed?

In general, a confidence interval gives an estimate together with a range expressing statistical uncertainty under the method used to calculate it. A narrow interval indicates more precision than a wide interval, while the interval’s location helps show which effect sizes remain compatible with the data. A p-value, when reported, summarizes how unusual data at least as extreme as those observed would be under a specified null model and assumptions. Neither measure alone communicates the full design quality or practical importance of an effect.

The registry record does not report a confidence interval, a p-value, a treatment contrast, or the primary group summaries. It also does not identify the inferential model or test used. Therefore, it is not possible to assess the statistical uncertainty around the primary comparison or to verify an analysis from the posted record. No model should be inferred solely from the description of the endpoint as a mean with standard deviation.

What does multiplicity mean for this study?

Multiplicity is the issue that arises when many outcomes, time points, groups, or comparisons are examined. In general, a larger family of statistical tests can increase the chance that at least one apparently notable result occurs by chance if each test is interpreted separately. Possible approaches include defining a primary comparison in advance, adjusting inference across a family of tests, or treating secondary findings as exploratory. The registry lists 37 outcome measures and multiple AC-170 concentrations, but does not report a multiplicity strategy or the actual analysis comparisons. It is therefore not possible to determine how multiplicity was addressed.

What do the planning assumptions tell the reader?

The registry’s planning-assumption text describes an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect, and distinguishes participant counts per arm from total event counts for time-to-event settings. These are planning assumptions, not evidence that the trial was designed using those assumptions. The registry does not report the trial’s own sample-size justification, and the numerical planning outputs are not reported in the registry record.

In general, sample-size calculations depend on assumptions about the target effect, variability, significance level, allocation, and analysis method. A planning illustration based on an observed effect is retrospective and cannot establish the design rationale used before enrollment. Such counts are planning aids, not observed power and not an estimate of the chance that a result is true. No planning count should be treated as an observed study result.

What can be checked from the posted record?

The record identifies an enrollment of 101 and reports no analyses. This combination means the intended design and endpoint can be described, but the primary result cannot be reproduced or independently checked using the registry information presented. The analysis model, handling of repeated time assessments, any covariate adjustment, and treatment of missing outcome data are not reported in the registry record. General statistical principles can explain why these details matter, but they cannot fill in the study-specific methods.

The endpoint has repeated assessment times after CAC, and scores are averaged over both eyes. General analyses of repeated measurements may account for correlation among observations from the same participant. However, the record does not state whether the time-specific scores were analyzed jointly, reduced to a single measure, or handled by another method. No particular approach can be attributed to the investigators from the registry description.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 37 outcome measures, including the primary itching endpoint and secondary measures of redness and chemosis at specified assessment times. The listed treatment groups also create more than one possible comparison with vehicle. In general, testing multiple outcomes, time points, or treatment contrasts raises a multiplicity issue: when many tests are considered, some apparently unusual results may occur by chance even if there is no underlying difference. A statistical plan can specify which outcome and contrast are primary and whether adjustments or other interpretive safeguards will be used.

The primary outcome is identified, but a multiplicity strategy is not reported in the registry record. The registry also lists zero analyses, so it does not provide enough information to identify which comparisons were performed or whether inferential claims were adjusted. There are no posted estimates or p-values for the listed outcomes to interpret in light of multiplicity.

Missing-data methods are not reported in the registry record. The record does not state how absent itching ratings, incomplete visits, or other unavailable measurements were handled. In general, the consequences of missing data depend on how much information is missing and on the reasons it is missing; those details are needed to judge possible bias. The primary outcome population is identified as Intent to Treat, but the definition alone does not explain how missing observations were addressed or how that population was implemented.

Other analysis-population details, including any per-protocol or safety population definitions, are not reported in the registry record. The reported at-risk counts for adverse events do not define the population used for efficacy analysis. Without these methods and the numerical outcome results, neither the influence of missing data nor the robustness of the efficacy analysis can be assessed.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The safety information reports serious adverse events for each listed group. The AC-170 0.05% group had 0 serious adverse events among 25 participants at risk; the AC-170 0.1% group had 0 among 26; the AC-170 0.24% group had 0 among 25; and the AC-170 0% group had 0 among 25. These are descriptive counts in the registry record. Zero reported events in a group does not establish that the risk is zero, nor does it demonstrate equivalence between groups.

The record also lists other adverse events affecting 6 participants in the AC-170 0.05% group, 3 in the AC-170 0.1% group, 4 in the AC-170 0.24% group, and 2 in the AC-170 0% group. These counts should not be confused with serious adverse events. The registry does not provide further event-level descriptions in the information recorded here, so their clinical nature and severity cannot be characterized from these counts alone.

Deaths are not reported in the registry record. The adverse-event figures are limited summaries and do not give comparative estimates or uncertainty intervals. They should be read as reported safety counts, not as a complete assessment of safety or a basis for claims about treatment effects.

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

The registry record establishes that a randomized, double-masked, vehicle-controlled, parallel-group study was conducted to evaluate AC-170 concentrations in a CAC model. It identifies ocular itching at the 16-hour duration-of-action assessment as the primary outcome and specifies how that symptom was scored. It also records selected safety counts. These details help define what the trial set out to examine.

They do not establish the result of the primary comparison. Numerical group summaries, treatment contrasts, confidence intervals, and p-values are not reported in the registry record. Without these estimates, the direction and magnitude of any difference are unknown from the posted information, as is its statistical precision. The absence of results cannot be interpreted as evidence that the groups had the same outcomes, nor as evidence that one treatment performed better.

The study’s endpoint is situated within a controlled allergen challenge and a specified assessment schedule. In general, evidence from a model-based challenge addresses the conditions and measurements of that model. It cannot automatically answer questions about outcomes in other contexts or at other times. The registry’s listed secondary outcomes broaden the planned measurement scope, but their numerical findings and analysis methods are not reported.

The sample-size planning assumptions described in the record should not be confused with the trial’s original design justification or with observed power. The registry does not report the trial’s own sample-size justification. Likewise, the stated randomized and masked design features are informative but do not replace details about implementation or analysis.

The safest statistical conclusion is therefore limited: the record describes the design, outcome definitions, enrollment, and some adverse-event counts, but does not provide the primary efficacy results needed to estimate or interpret treatment differences. No claim about efficacy, equivalence, or comparative safety follows from the information recorded.

13. Why This Trial Matters Statistically

This trial is statistically notable for its structured comparison of three AC-170 concentrations with a vehicle group in a controlled CAC setting. Its randomized, double-masked, parallel-group design gives a clear framework for asking how an outcome differs across assigned groups. The primary endpoint is also defined with useful specifics: it concerns participant-rated ocular itching, averages scores over both eyes, and is tied to a stated post-instillation challenge and assessment schedule.

Those design and measurement details illustrate why an endpoint definition matters. A symptom score is not interchangeable with an examiner-rated sign, and an outcome measured at one specified challenge time does not automatically represent symptoms at other times. The record separately lists redness and chemosis outcomes, emphasizing that multiple clinical measures can be collected within one study. In general, such breadth can help characterize different aspects of a condition, while also making a clear analysis plan important.

The record also demonstrates the difference between a trial description and a statistical result. Enrollment, treatment groups, phase, endpoint definitions, and adverse-event counts are available, but numerical efficacy estimates are not. Without those estimates, the main comparison cannot be evaluated for size or precision. A well-defined question is not itself an answer to that question.

For biostatistical interpretation, the missing analysis information is consequential. The registry does not report the inferential method, handling of missing outcomes, or multiplicity strategy, and it lists zero analyses. Those omissions limit reproducibility and prevent readers from assessing how the outcome data were converted into conclusions. The case therefore highlights the value of reporting group summaries, treatment contrasts, uncertainty intervals, and methods alongside the design record.

The statistical importance lies in both what is specified and what remains unavailable. The endpoint and design are sufficiently described to frame the intended comparison, but the posted record does not permit an efficacy assessment.

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.

A key limitation is that the registry record does not report numerical results for the primary outcome. Group means, standard deviations, treatment contrasts, confidence intervals, and p-values are absent, so the magnitude, direction, and precision of any difference cannot be assessed. The record lists zero analyses, further limiting the ability to determine which statistical comparisons were conducted.

The methods description is incomplete for independent interpretation. The randomization procedure, allocation concealment, masking implementation, analysis model, and handling of repeated assessments are not reported in the registry record. Missing-data methods and the operational definition of the Intent to Treat analysis are also not reported. Although the primary population is named, that label alone does not clarify how incomplete outcome data or protocol deviations were handled.

The registry lists 37 outcome measures and several treatment concentrations, but a multiplicity strategy is not reported. This leaves unclear how the primary and secondary comparisons were distinguished for inference. Secondary outcome names are available, but their numerical results are not.

The study is described as single-center and uses the CAC model. These features define the setting and assessment context; the registry does not provide enough information to judge how findings might extend beyond that model. In any case, no efficacy estimates are posted to assess within-study effects. The enrollment total does not replace outcome results, and the safety counts are descriptive rather than comparative estimates. Death counts are not reported in the registry record.

Finally, the planning assumptions in the record are described as an illustration based on an observed effect, not as the trial’s own design rationale. The trial’s sample-size justification is not reported in the registry record. These limitations mean that the study can be characterized from its registration details, but its efficacy findings cannot be independently evaluated from the posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy of AC-170 for the Treatment of Allergic Conjunctivitis in the Conjunctival Allergen Challenge (CAC) Model — NCT01332188.
• Registry record last updated 2017-08-30; status last verified 2017-07.
• Results first posted 2017-08-30.
• 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

The registry record describes a completed, single-center, randomized, double-masked, vehicle-controlled, parallel-group study of AC-170 for allergic conjunctivitis in the CAC model. It lists Phase 2 and Phase 3, enrollment of 101, and four groups: AC-170 0.05%, AC-170 0.1%, AC-170 0.24%, and AC-170 0% vehicle.

The primary outcome is mean ocular itching at the 16-hour duration-of-action CAC assessment, based on participant ratings at 3, 5, and 7 minutes and averaged over both eyes. The primary population is identified as Intent to Treat. The record lists 37 outcome measures and zero analyses.

Serious adverse events are recorded as zero in each group; other adverse-event counts are also listed. Numerical efficacy results, death counts, detailed analysis methods, missing-data methods, and the trial’s sample-size justification are not reported in the registry record. The posted information therefore describes the intended comparison but does not permit an assessment of the primary treatment effect.