RTA 408 Ophthalmic Suspension for the Treatment of Ocular Inflammation and Pain Following Ocular Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RTA 408 Ophthalmic Suspension for the Treatment of Ocular Inflammation and Pain Following Ocular Surgery (NCT02065375), a randomized phase 2 study. The primary outcome is Absence of Anterior Chamber Cells at Day 15 (Visit 5).

2. Clinical Question

The trial asked whether either of two concentrations of omaveloxolone ophthalmic suspension could be used to address inflammation and pain following ocular surgery. Its primary outcome was the count of participants with absence of anterior chamber cells at Day 15, a measure of ocular inflammation. The registry record also describes safety information for the study eye, the non-study eye, and non-ocular adverse events.

The comparison was between omaveloxolone ophthalmic suspension 1.0%, omaveloxolone ophthalmic suspension 0.5%, and placebo. The registry describes one drop instilled into the study eye twice daily for 14 days, beginning 24 ± 6 hours after surgery. The central statistical question is whether the proportion of participants meeting the primary endpoint differed across the randomized treatment groups. The posted record does not report the group-specific primary endpoint counts or a treatment-effect estimate, so that comparison cannot be evaluated from the endpoint description alone.

This question is about a measured postoperative inflammation outcome. It is distinct from asking whether pain changed, because the posted primary endpoint is absence of anterior chamber cells, not a pain score. The brief summary includes both inflammation and pain as the study purpose, but the registry record does not give a separate pain result in the primary endpoint description.

3. Trial Design

This was a multicenter, randomized, dose-ranging, double-masked, placebo-controlled phase 2 study with a parallel-group model. The registry record lists an enrollment of 109 participants and a completed status. The study start is recorded as 2014-02-28, and primary completion as 2014-09-30. These dates describe the registry record; they do not establish the timing of any later analysis or publication.

Participants were assigned to omaveloxolone ophthalmic suspension 1.0%, omaveloxolone ophthalmic suspension 0.5%, or placebo. In each active group, the stated regimen was a single drop in the study eye twice daily, approximately 12 hours apart, for 14 days. Treatment began 24 ± 6 hours after surgery. The placebo arm received a single drop of the vehicle on the same schedule. The registry identifies the study as double-masked but does not describe exactly who was masked or how masking was maintained.

Randomization supports comparisons between assigned groups by reducing systematic differences at baseline in expectation. It does not guarantee that groups are identical in a particular trial, and it does not by itself establish the size or precision of a treatment effect. The registry record does not report the randomization procedure, allocation concealment details, stratification factors, or group sizes specifically for the primary endpoint analysis. The adverse-event entries list different numbers at risk for the three treatment groups, but those entries should not be substituted for an endpoint analysis population without further record detail.

The trial is dose-ranging because it included two stated concentrations of the active suspension. A placebo arm allows an assessment of each active regimen against the vehicle, while the two active arms also make a dose comparison possible in principle. However, the registry record does not report the planned contrasts or the statistical procedure for comparing the groups. It also does not report a sample-size justification, interim analyses, or a detailed statistical analysis plan. The stated planning illustration assumptions are not a substitute for the trial’s own design justification.

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

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population (all randomized patients with available data). Data for visits after a patient was discontinued for lack of efficacy were imputed as failures and missing data were imputed using last observation carried forward.

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: Intent-to-treat population (all randomized patients with available data)

6. Primary Endpoint

The registry lists the primary outcome as Absence of Anterior Chamber Cells at Day 15 (Visit 5), measured over 15 days after the participant receives the first dose.

The primary endpoint is the count of participants with absence of anterior chamber cells at Day 15, identified as Visit 5. The description says white blood cells were counted and explains that a healthy eye should not have blood cells present in the anterior chamber. A “Yes” response indicates absence of anterior chamber cells. The timeframe is 15 days after the participant receives the first dose.

This endpoint is used as a measure of ocular inflammation after surgery. Counting cells turns an examination finding into an outcome that can be classified for each participant, then compared across randomized groups. In general, a binary endpoint such as presence or absence makes the group result interpretable as the number of participants who meet a defined clinical criterion. Its meaning depends on the assessment method, timing, and rules for handling incomplete follow-up.

The registry specifies that data for visits after a participant was discontinued for lack of efficacy were imputed as failures, and missing data were imputed using last observation carried forward. These rules affect how the endpoint is assigned when a Day 15 observation is unavailable. The registry record does not report the number of missing observations, the number discontinued for lack of efficacy, or the group-specific endpoint counts. It therefore does not permit an assessment of how much these rules influenced the posted comparison.

The endpoint is not itself a direct measure of pain. Although the study’s stated purpose includes inflammation and pain following ocular surgery, the primary outcome described in the record is the absence of anterior chamber cells. Any distinct pain measure or its results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how a study question is converted into a comparison and how uncertainty is described. In this trial, the primary endpoint is a count of participants who had absence of anterior chamber cells at Day 15. Although it is reported as a count, the underlying participant-level status is binary: each participant either meets the stated criterion or does not. The registry record does not provide the arm-level counts or the statistical model used for the primary comparison.

What randomization contributes

General explanation: random assignment is intended to make treatment groups comparable with respect to both measured and unmeasured characteristics, on average. It provides a basis for interpreting between-group differences as associated with assignment, subject to adherence, follow-up, measurement, and analysis considerations. Randomization does not ensure that any particular study has perfectly balanced groups, and it does not remove uncertainty from the estimated effect. The registry identifies randomized allocation, but does not report the method used to generate or conceal the assignment sequence.

Reading a binary endpoint

General explanation: for a binary endpoint, analysts commonly describe the number meeting the criterion and the number assessed in each group. A treatment contrast can be expressed on different scales, such as a difference in proportions or a relative measure. The scale matters because it changes the interpretation of the estimate. The registry record does not report the primary endpoint counts, the treatment contrast, or the chosen effect scale, so no such result can be interpreted from the available endpoint description.

A confidence interval would communicate uncertainty around an estimated contrast. It is not a guarantee that the true value lies within the displayed bounds, but a statistical interval constructed under stated assumptions. A narrow interval generally indicates greater precision than a wide interval, though precision does not establish clinical importance. A p-value addresses how unusual the observed data would be under a specified null hypothesis and analysis model. It does not state the probability that the null hypothesis is true, and it does not measure the size of an effect. Neither confidence intervals nor p-values for the primary endpoint are reported in the registry record.

Planning assumptions are not trial results

The registry describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The planning illustration considers an effect to detect as a stated fraction of the observed effect. Those are assumptions for a planning calculation, not evidence that the trial was designed using those assumptions. The record does not report the trial’s sample-size justification. Any sample-size illustration is a planning aid, not observed power and not a substitute for the treatment-effect estimate and its uncertainty.

General explanation: power calculations depend on assumptions about the effect, variability or event frequency, significance threshold, allocation, and analysis. If the assumed effect differs from the effect that would be relevant in practice, the resulting planning number may not answer the practical design question. In this record, there is no basis to infer a protocol rationale or to treat an illustrative calculation as a description of the study’s original planning.

Multiplicity and model choice

Testing multiple treatment contrasts, endpoints, or time points creates a multiplicity issue: the chance of at least one apparently unusual result can increase when many hypotheses are examined. Statistical approaches may control that risk using prespecified testing strategies or adjustment procedures. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which contrasts were prespecified. The presence of two active concentrations and a placebo makes the intended comparisons important to identify, but their statistical handling is not reported.

Model choice also matters. For binary outcomes, an analysis might compare proportions directly or use a regression model, possibly with covariate adjustment. Different methods can yield different estimates or uncertainty measures, especially with limited data or uncommon outcomes. The registry record does not report the model, covariates, or variance method used for the primary endpoint. No method should be inferred from the fact that the study was randomized or from the endpoint being binary.

Over-dispersion and count outcomes

General explanation: over-dispersion arises when observed variation exceeds what a chosen statistical model expects. It can matter for count data or clustered observations, because an analysis that assumes too little variation may understate uncertainty. The primary endpoint is described as a count of participants meeting a binary criterion, not as a repeated event count. The record does not report an over-dispersion assessment or a model that would require one, so this concept cannot be used to infer how the trial’s endpoint was analyzed.

Overall, the registry supports a clear description of the endpoint and some analysis assumptions used for a planning illustration, but does not provide the detailed statistical plan or the primary results needed to reproduce or evaluate the efficacy analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes multiple treatment groups, with two omaveloxolone concentrations and placebo, and identifies the primary endpoint as absence of anterior chamber cells at Day 15. It does not report which group contrasts were designated for formal testing, whether comparisons were ordered in a hierarchy, or whether any adjustment for testing multiple hypotheses was used. Those details matter because evaluating more than one dose against placebo, or examining multiple outcomes and time points, can affect the interpretation of nominal statistical evidence. The approach to multiplicity is not reported in the registry record.

The primary population is described as the intent-to-treat population, defined in the record as all randomized patients with available data. At the same time, the outcome description says that visits after discontinuation for lack of efficacy were imputed as failures and that missing data were imputed using last observation carried forward. These statements describe the population and certain outcome-handling rules, but the record does not report how many participants were missing, how many discontinued, or how these counts differed by group.

General explanation: last observation carried forward uses an earlier recorded observation in place of an unavailable later measurement. It can simplify the analysis, but it assumes that carrying the prior value forward is an adequate representation of the later outcome. That assumption may be unsuitable when outcomes change over time. Treating visits after discontinuation for lack of efficacy as failures is a separate rule that assigns an unfavorable endpoint status in those circumstances. The record does not report sensitivity analyses that test whether conclusions change under alternative missing-data assumptions.

The registry does not report a detailed analysis population flow, reasons for missingness by group, or a comparison of results under alternative analysis sets. It is therefore not possible to assess the influence of missing data, the robustness of the imputation rules, or whether the analysis followed a prespecified strategy. A sample-size justification, interim analysis plan, and full statistical analysis plan are also not reported in the registry record.

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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists safety counts separately for the study eye, the non-study eye, and non-ocular adverse events. For the 1.0% group, 37 participants were listed at risk for each category: zero serious events and 18 other events for the study eye, zero serious events and zero other events for the non-study eye, and zero serious events and two other events for non-ocular events. For the 0.5% group, 33 participants were listed at risk: zero serious events and 15 other events for the study eye, zero serious events and two other events for the non-study eye, and zero serious events and two other events for non-ocular events. For placebo, 39 participants were listed at risk: zero serious events and 13 other events for the study eye, zero serious events and one other event for the non-study eye, and zero serious events and one other event for non-ocular events.

The record lists zero deaths in each group and no serious-event terms. These are descriptive registry counts. “Other” events are distinct from serious events in the listing; the record does not provide the specific terms for those other events. Nor does it clarify whether the counts refer to people, event occurrences, or participants with at least one event across each category. The eye-specific and non-ocular categories should therefore be read as separate reported categories, not combined into an overall participant count.

Zero recorded serious events does not establish that serious events cannot occur, and these counts alone do not establish a safety difference between regimens. The groups have different numbers at risk, and the registry does not report a comparative safety analysis or uncertainty estimates.

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

The registry record allows readers to identify the question studied: whether two concentrations of omaveloxolone ophthalmic suspension could be compared with placebo for postoperative ocular inflammation and pain, with absence of anterior chamber cells at Day 15 specified as the primary endpoint. It also records the dosing schedule, the randomized double-masked phase 2 design, missing-data rules, and descriptive adverse-event counts.

It does not report the primary endpoint results by treatment group. Without those counts or a treatment-effect estimate, readers cannot determine the observed direction or size of the primary comparison, or how precisely it was estimated. The lack of a reported comparison should not be interpreted as evidence of no difference. Likewise, the registry’s description of the study purpose is not a result, and the primary endpoint should not be conflated with pain outcomes that are not detailed in that endpoint description.

The adverse-event information is also limited. It shows zero serious adverse events and zero deaths in the listed groups, alongside counts for other adverse events divided by eye and non-ocular categories. These observations describe what the registry lists; they do not establish that one regimen is safer than another. The record does not provide event-level terms for the other events, comparative estimates, or uncertainty around safety differences.

General explanation: a trial result is most informative when the estimated effect is read together with its uncertainty, the endpoint definition, the analysis population, and the handling of missing data. Statistical significance alone, if reported, would not establish clinical importance. Here, the primary efficacy estimate and its uncertainty are not reported, so neither statistical significance nor clinical importance can be assessed from the registry record.

The study record is therefore useful for understanding the design and what was intended to be measured, but it is insufficient for a conclusion about efficacy. It is also insufficient for a comparative safety conclusion. These limits concern the information reported in the registry record and do not describe results from other sources.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and an available result are both necessary for statistical interpretation. The registry specifies a concrete primary outcome: participants with absence of anterior chamber cells at Day 15. It also identifies how observations following discontinuation for lack of efficacy and other missing observations were handled. Those details help define what the endpoint means and how it was intended to be assigned.

At the same time, the registry record does not give the group-specific primary outcome counts or a treatment-effect estimate. A study can have a named endpoint, randomized groups, and a detailed schedule, yet still leave readers unable to judge the central comparison if the results are absent from the record. Enrollment alone cannot fill that gap; it does not reveal how many participants met the endpoint or the precision of an estimated contrast.

The dose-ranging structure also makes transparent reporting of the comparison strategy important. The two active concentrations and placebo create more than one potentially relevant contrast. Without a reported testing hierarchy or multiplicity approach, readers cannot establish how evidence across comparisons was intended to be interpreted. This is a general issue in trials with multiple treatment arms, not evidence that a particular procedure was or was not used in this study.

Finally, the safety listings show why categories and denominators must be read carefully. The counts distinguish study-eye, non-study-eye, and non-ocular events, and include different numbers at risk across groups. They do not by themselves yield an overall comparative safety estimate. Keeping descriptive counts separate from efficacy conclusions prevents the safety record from being used as a substitute for the missing primary result.

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 main trial-specific limitation for interpretation is that the registry record does not report arm-level primary endpoint results. It therefore does not provide the observed counts needed to compare the 1.0% suspension, the 0.5% suspension, and placebo on absence of anterior chamber cells at Day 15. The effect estimate, its uncertainty, and a primary-endpoint p-value are not reported in the registry record.

The outcome description includes both a day-specific endpoint and rules for handling unavailable observations. The number of participants affected by last observation carried forward or by the failure imputation after discontinuation for lack of efficacy is not reported. Without those details or sensitivity analyses, readers cannot assess the extent to which the endpoint comparison might depend on the missing-data rules.

The record does not provide the randomization procedure, allocation concealment details, analysis model, covariate strategy, multiplicity procedure, or statistical analysis plan. It also does not report a sample-size justification, interim analyses, or the reasons for missing data. These omissions prevent a detailed appraisal of how the primary comparison was planned and conducted.

Safety information is presented in separate eye-specific and non-ocular categories. The registry does not report the terms of the other adverse events in these entries or clarify whether the listed counts represent unique participants or event occurrences. The counts at risk differ across treatment groups, and no comparative safety estimates are reported. The record also does not provide a separate pain result in the primary endpoint description. These limitations restrict conclusions to what is explicitly recorded, rather than establishing that any unreported analysis was not performed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: RTA 408 Ophthalmic Suspension for the Treatment of Ocular Inflammation and Pain Following Ocular Surgery — NCT02065375.
• Registry record last updated 2025-06-03; status last verified 2025-05.
• Results first posted 2023-04-19.
• 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 record describes NCT02065375, a completed, multicenter, randomized, double-masked, placebo-controlled phase 2 dose-ranging study of omaveloxolone ophthalmic suspension following ocular surgery. Enrollment was 109. Participants were assigned to 1.0%, 0.5%, or placebo, with a single drop instilled in the study eye twice daily for 14 days, beginning 24 ± 6 hours after surgery.

The primary endpoint was the count of participants with absence of anterior chamber cells at Day 15. The record describes failure imputation after discontinuation for lack of efficacy and last observation carried forward for missing data. It also lists serious and other adverse-event counts by study eye, non-study eye, and non-ocular category. Serious adverse events and deaths are listed as zero in the groups.

Arm-level primary endpoint results, comparative effect estimates, confidence intervals, p-values, multiplicity methods, and a detailed statistical analysis plan are not reported in the registry record. The posted information supports a description of the design and outcome definitions, but not an efficacy comparison or comparative safety conclusion.