An Open-Label Extension of a Phase 3 Study of OTX-101 in the Treatment of Keratoconjunctivitis Sicca: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Extension of a Phase 3 Study of OTX-101 in the Treatment of Keratoconjunctivitis Sicca (NCT02845674), a na phase 3 study. The primary outcome is Adverse Events.

2. Clinical Question

The central question is how many participants reported adverse events during the 40-week open-label extension of OTX-101 0.09% for keratoconjunctivitis sicca. The registry record identifies the primary outcome as the count of participants reporting any adverse events. This is a safety question, not a test of comparative efficacy.

The record reports 55 participants with any adverse event in Group 1 and 69 in Group 2; each group had 129 participants at risk for this outcome. These are descriptive counts. Because everyone received the same open-label treatment during the extension, differences between the groups cannot be read as a randomized estimate of treatment effect. The groups carry forward their earlier treatment histories, and the registry record does not report an analysis that adjusts for those histories or other differences.

3. Trial Design

NCT02845674 is a Phase 3, completed, open-label extension study of OTX-101 in keratoconjunctivitis sicca. Its official title identifies it as an extension of a randomized, multicenter, double-masked, vehicle-controlled study, but those design features describe the earlier study, not the extension itself. The extension is recorded as having no masking and a single-group model, with allocation listed as not applicable.

The registry record states that the extension enrolled participants from Study OTX-101-2016-001 (NCT02688556) and was intended as a safety extension. Enrollment is listed as 258. The safety population is divided into Group 1 and Group 2 according to whether participants received masked OTX-101 0.09% or vehicle, respectively, in the earlier study. In the extension, all participants received open-label OTX-101 0.09%. Each group has 129 participants at risk for the reported adverse-event outcomes.

The listed study dates are 2016-07-29 for the start and 2017-08-15 for primary completion. The primary outcome timeframe is 40 weeks. The registry record does not report the extension’s detailed visit schedule, eligibility criteria, treatment administration instructions, or procedures for collecting adverse-event information.

It is important to distinguish the extension from its predecessor. Randomization and masking in the earlier study do not make the extension a randomized comparison. Within the extension, treatment was open-label and there was no concurrent vehicle arm. The two groups are useful for describing event counts by prior-study treatment history, but they do not provide a like-for-like control comparison of current treatment.

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: Group 1 and Group 2 consisted of subsets of subjects who received masked treatment with OTX-101 0.09% or with Vehicle, respectively, in OTX-101-2016-001. All subjects received open-label treatment with OTX-101 0.09% in OTX-101-2016-002.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety population: Group 1 and Group 2 consisted of subsets of subjects who received masked treatment with OTX-101 0.09% or with Vehicle, respectively, in OTX-101-2016-001. All subjects received open-label treatment with OTX-101 0.09% in OTX-101-2016-002.

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; Group 1 and Group 2 consisted of subsets of subjects who received masked treatment with OTX-101 0.09% or with Vehicle, respectively, in OTX-101-2016-001. All subjects received open-label treatment with OTX-101 0.09% in OTX-101-2016-002

6. Primary Endpoint

The registry lists the primary outcome as Adverse Events, measured over 40 weeks.

The primary endpoint is the number of participants reporting any adverse events during the 40-week timeframe. It is expressed as a count of participants, rather than as a measure of event severity, duration, or frequency. A participant is counted for this endpoint if they reported an adverse event; the registry record does not state how many separate events each participant could have had or how repeated events were handled.

As a general statistical principle, a broad adverse-event endpoint is used to describe the overall occurrence of events recorded during a study. It can help characterize the safety experience of participants during the specified follow-up period. A participant count is different from an event count: one participant may experience more than one event, but the primary outcome is defined as the number of participants reporting any adverse event.

The registry record reports 55 participants with any adverse event in Group 1 and 69 in Group 2. Each group had 129 participants at risk. These counts describe the observed safety experience in this extension; they do not establish whether an event was caused by treatment. The registry record does not report an adverse-event definition, severity grading approach, attribution procedure, or a statistical comparison for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record lists one primary outcome measure: adverse events, measured as the count of participants reporting any adverse event over 40 weeks. The reported outcome is a participant-level count. It is not a count of all events, and the record does not state whether event counts were also analyzed. The posted results give the number at risk and the number with an event for each of the two prior-treatment groups.

What does a participant count represent?

As a general statistical explanation, a binary outcome classifies each participant according to whether the event occurred during the defined observation period. Reporting the number with an event is a direct description of the observed participants. It should be distinguished from a rate based on person-time, from a count of repeated events, and from a time-to-event analysis. The registry record does not report those other measures for the primary outcome.

The listed primary measure is broad: any adverse events. The record does not provide a detailed event definition, rules for coding events, severity categories, or attribution to treatment. Those omissions matter because a count depends on what qualifies as an event and how it is collected. Without those details, the count can be described as posted, but the underlying classification process cannot be independently characterized from the registry record.

Why is the group structure not a treatment comparison?

Group 1 and Group 2 were defined by treatment received in the earlier OTX-101-2016-001 study. All participants received open-label OTX-101 0.09% in this extension. In a randomized comparison, treatment assignment creates groups intended to support a fair comparison of outcomes. Here, the registry record lists allocation as not applicable and describes a single-group extension. The predecessor study’s randomization does not create a concurrent randomized control group in the extension.

As a general principle, a treatment contrast requires an appropriate comparison and an analysis that reflects the design. Counts in groups distinguished by previous treatment may be useful descriptively, but their difference cannot be attributed to the current treatment solely from this record. The registry record reports no adjusted analysis, confidence interval, p-value, or other inferential result for the primary outcome.

What does the sample-size illustration mean?

The planning illustration is not the trial’s own design justification and is not observed power. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. The registry record does not report the trial’s sample-size justification. Because the extension is not a randomized two-arm comparison, such a hypothetical planning framework should not be mistaken for evidence that the extension was designed to test a treatment contrast.

As a general explanation, a sample-size calculation is a planning exercise that asks how many participants would be needed under specified assumptions to detect a target effect with a chosen operating characteristic. It does not describe what was observed, and it cannot establish that a study had a particular probability of detecting an effect after the results are known. The planning assumptions are therefore distinct from the observed participant counts in this extension.

What is not reported about the analysis?

The registry record reports zero analyses. It does not report a statistical analysis plan, inferential methods, multiplicity procedures, handling of missing observations, or a detailed definition of the analysis populations beyond the safety-population description. These are not details that can be inferred from the study title or from the predecessor study’s design. The posted counts should consequently be read as descriptive registry results, without adding assumptions about unreported methods.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Group 1", "Group 2")
n      <- c(129, 129)
events <- c(68, 81)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Group 1  129  68  52.7  43.7  61.6  44.1  61.1  44.1  61.1
ARM  Group 2  129  81  62.8  53.8  71.1  54.2  70.6  54.2  70.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one outcome measure, adverse events, and reports zero analyses. It does not report a prespecified hierarchy of outcomes, a multiplicity adjustment, or a plan for controlling the chance of false-positive findings across multiple statistical tests. Since no inferential analyses are reported, there are no reported p-values to interpret in relation to multiplicity.

As a general statistical explanation, multiplicity arises when several hypotheses or outcomes are tested. If each is judged independently at a chosen significance threshold, the chance of at least one false-positive finding can increase. Methods for managing this issue depend on the analysis plan and the questions being tested. The registry record does not state that such a plan was used, so none should be assumed.

The safety population is described as Group 1 and Group 2, subsets based on masked treatment received in the earlier study; all participants received open-label OTX-101 0.09% in the extension. The record reports 129 participants at risk in each group for the adverse-event outcomes. It does not report whether those at-risk counts include every enrolled participant throughout follow-up or how withdrawal and incomplete observation affected the endpoint.

Missing-data methods, the number of participants with incomplete safety follow-up, and reasons for missing observations are not reported in the registry record. As a general principle, missing outcome information can affect interpretation if the participants without recorded outcomes differ from those with complete observation. Without details on follow-up completeness and handling of missing data, that potential cannot be assessed from the posted results.

12. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: osteoarthritis (1.6%), cerebrovascular accident (1.6%), wound dehiscence (0.8%), dehydration (0.8%), femur fracture (0.8%).

The serious adverse-event figures are participant counts, not estimates of comparative risk. Group 1 had 4 participants with serious adverse events among 129 at risk; Group 2 also had 4 among 129 at risk. The record reports zero deaths in each group. All participants received open-label OTX-101 0.09% during the extension, so the group labels indicate earlier masked treatment rather than current treatment assignment.

The listed serious-event terms include osteoarthritis and cerebrovascular accident, each at 1.6%, followed by wound dehiscence, dehydration, and femur fracture, each at 0.8%. The registry record does not give the event counts for each term or specify the denominator behind those percentages. These term listings should not be treated as a complete account of all serious events or as evidence that treatment caused an event.

As a general statistical point, safety counts describe what was recorded in the observed participants and follow-up period. They do not alone establish whether an event is attributable to a treatment, and a lack of a reported event is not proof that it cannot occur. The registry record does not report comparative statistical analyses, follow-up completeness, or event-attribution methods for these serious-event results.

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

The posted results describe adverse events reported during a 40-week open-label extension in which all participants received OTX-101 0.09%. The primary outcome is the number of participants reporting any adverse event. The record reports 55 in Group 1 and 69 in Group 2, with 129 participants at risk in each group. It also reports 4 participants with serious adverse events in each group and zero deaths in each group.

These findings are descriptive. The groups were defined by masked treatment received in the earlier study, not by randomized assignment in the extension. Because both groups received the same open-label treatment during this study, the group counts do not provide a like-for-like treatment comparison. The posted results do not include confidence intervals, p-values, adjusted estimates, or a formal comparison.

The record therefore does not establish that OTX-101 caused or prevented any reported event, nor does it establish a comparative safety effect. It also does not report an efficacy outcome in this extension. The title’s reference to efficacy in the treatment of keratoconjunctivitis sicca does not change the stated purpose of this extension as a safety study or the primary endpoint.

As a general statistical principle, interpretation depends not only on the observed counts but also on study design, outcome definitions, follow-up, and analysis. The registry record does not report enough detail to evaluate event attribution, missing safety observations, or the precision of a comparison between the prior-treatment groups. The appropriate reading is limited to the reported safety experience in the enrolled participants, with the limitations of an open-label extension and no concurrent control.

14. Why This Trial Matters Statistically

This study is statistically instructive because an extension can preserve participant follow-up while changing the question that can be answered. The predecessor study is described as randomized, multicenter, double-masked, and vehicle-controlled. The extension, by contrast, is open-label, has allocation listed as not applicable, and is recorded as a single-group study. Design features from the earlier trial should not be carried forward as though they governed this extension.

The two safety groups provide context about prior masked treatment, but both received OTX-101 0.09% during the extension. That structure illustrates why a group label is not itself evidence of a randomized comparison. Descriptive counts can characterize recorded events in each group, while causal comparisons require a design and analysis that support attribution.

The endpoint also illustrates the distinction between people and events. The primary outcome counts participants reporting any adverse event, rather than the total number of events. Those measures answer different questions. The record does not report additional detail on recurrent events, severity, or attribution, so interpretation must remain tied to the participant count that is defined.

Finally, the registry record contains descriptive safety results but reports zero analyses. This makes it especially important to distinguish observed counts from inferential evidence. No precision estimate or formal comparison is reported. The record is useful for describing what was posted for this extension, while leaving important questions about analysis methods and completeness of follow-up unanswered.

15. 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 limitation is the absence of a concurrent control group. Although Group 1 and Group 2 reflect different masked treatments in the predecessor study, both received open-label OTX-101 0.09% in the extension. The registry record explicitly describes the extension as a single-group study with allocation not applicable. The groups are therefore not a like-for-like randomized comparison of current treatment.

The primary result is a count of participants reporting any adverse event over 40 weeks. The record does not report the detailed adverse-event definition, collection procedures, severity grading, attribution methods, or handling of multiple events in one participant. It also does not report confidence intervals, p-values, adjusted estimates, or a statistical comparison.

The safety population description identifies the earlier-study treatment history used to define the groups, but detailed participant characteristics and analyses of group comparability are not reported in the registry record. Follow-up completeness, discontinuations, missing safety observations, and methods for handling missing data are also not reported. These gaps limit assessment of how fully the posted counts represent the intended observation period.

The serious-event term listings give percentages but do not report the term-specific counts or explain the denominators. The registry record reports zero deaths in both groups, but it does not provide broader details on ascertainment or follow-up. Finally, the record does not report the trial’s sample-size justification or a statistical analysis plan. These omissions preclude conclusions about the precision or comparative meaning of the results beyond the descriptive counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open-Label Extension of a Phase 3 Study of OTX-101 in the Treatment of Keratoconjunctivitis Sicca — NCT02845674.
• Registry record last updated 2021-11-19; status last verified 2021-11.
• Results first posted 2018-12-14.
• 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.

19. Record Summary

NCT02845674 is a completed Phase 3 open-label extension for keratoconjunctivitis sicca. The registry record describes it as a safety extension enrolling participants from OTX-101-2016-001 (NCT02688556). All participants received open-label OTX-101 0.09%, described as a 0.09% cyclosporine nanomicellar solution.

The primary outcome was the number of participants reporting any adverse event over 40 weeks. The safety population was divided according to prior masked treatment in the earlier study. Each group had 129 participants at risk; any adverse events were reported for 55 participants in Group 1 and 69 in Group 2. Serious adverse events were reported for 4 participants in each group, and zero deaths were reported in each group.

The extension was not a randomized comparison, and the registry record reports zero analyses. The posted counts should be interpreted as descriptive safety results, not as evidence of a comparative treatment effect.