Phase 2/3 Dose-Ranging Study of the Safety and Efficacy of OTX-101 in the Treatment of Keratoconjunctivitis Sicca: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2/3 Dose-Ranging Study of the Safety and Efficacy of OTX-101 in the Treatment of Keratoconjunctivitis Sicca (NCT02254265), a randomized phase 2, phase 3 study. The primary outcome is Conjunctival Staining.

2. Clinical Question

The primary measure is a staining score recorded by the investigator for areas of each eye. Its stated scale runs from 0, meaning no punctate stain in a zone, to 3, meaning densely concentrated micropunctate stain spots. The posted primary results describe mean change from baseline, rather than the day-84 score alone.

The statistical comparison is between each concentration and the vehicle group. This setup addresses whether the average change in staining score differed between assigned groups over the stated treatment period. The record also lists tear film break-up time, corneal staining score, Schirmer's Test, and patient satisfaction as secondary outcomes. Those measures provide additional outcome domains, but they do not replace the primary comparison or establish a broader treatment effect on their own.

The registry record does not report a minimum clinically important difference for the primary score, nor does it explain how a change of a particular size should be interpreted by patients or clinicians. Statistical differences therefore need to be read alongside the score's scale, the uncertainty in the estimates, and the trial's reporting limitations.

3. Trial Design

This was a randomized, multicenter, double-masked, vehicle-controlled dose-ranging study in Phase 2/3. The registry record lists quadruple masking and a parallel-group model. Enrollment was 455. The study is marked completed, with a listed start of 2014-09 and primary completion of 2015-05.

Three groups are described: OTX-101 0.05%, OTX-101 0.09%, and vehicle. Each regimen was one drop in both eyes twice daily for 84 days. The two active concentrations were each compared with the vehicle group for the posted primary outcome. The parallel-group model means the registry describes assigned groups followed under their respective regimens, rather than a crossover between treatments.

Randomization can help balance measured and unmeasured characteristics between groups on average, while masking is intended to reduce influences of treatment knowledge on care, assessment, or reporting. The record identifies these design features but does not report the random sequence method, allocation concealment procedures, which parties were masked, or how masking was maintained.

The posted primary outcome is mean change from baseline to day 84 in the lissamine green conjunctival staining score for the designated study eye. The stated analysis population is intent to treat, with last observed carried forward. The record lists six outcome measures and four posted secondary outcomes. It does not describe a trial-specific statistical analysis plan, justify the sample size, or give details of outcome-assessment timing beyond the stated baseline-to-84-day timeframe.

The primary completion date indicates when primary outcome collection was completed in the record, not necessarily when all study activity ended. A full study completion date is 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent to treat population, last observed carried forward approach

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

6. Primary Endpoint

The registry lists the primary outcome as Conjunctival Staining, measured over Baseline to 84 days.

The primary endpoint is mean change from baseline to day 84 in lissamine green conjunctival staining score in the designated study eye. The investigator records scores for areas of each eye on a scale from 0, no punctate stain in a zone, to 3, densely concentrated micropunctate stain spots. The registry describes the outcome as a score on a scale and reports group means and standard deviations.

Staining is used as an observable measure of the ocular surface condition being studied. A change score summarizes how the recorded score at follow-up compares with baseline for participants in each group. Because higher scale descriptions reflect more visible staining, a more negative change corresponds numerically to a larger reduction in score. That numerical direction does not, by itself, establish how noticeable or important the change is to participants; a threshold for clinical importance is not reported in the registry record.

For the primary outcome, the registry specifies the intent-to-treat population and a last observed carried forward approach. This means the posted summary is intended to include the assigned population while carrying forward the last available observation under the stated approach. The record does not explain how many measurements were missing or the timing and reasons for missingness, so the effect of that procedure on the estimate cannot be assessed from the listed information alone.

7. Results Posted in the Registry

• OTX-101 0.05%: mean -1.90 versus -1.20 on control; difference -0.70 (95% CI -1.19 to -0.21), standardized effect d = -0.32; z-test p = 0.005.
• OTX-101 0.09%: mean -1.80 versus -1.20 on control; difference -0.60 (95% CI -1.10 to -0.10), standardized effect d = -0.27; z-test p = 0.018.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Tear Film Break up Time (TBUT)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • OTX-101 0.05%: mean 0.43 versus 0.39 on control; difference 0.04 (95% CI -0.44 to 0.52), standardized effect d = 0.02; z-test p = 0.871.
  • OTX-101 0.09%: mean 0.53 versus 0.39 on control; difference 0.14 (95% CI -0.41 to 0.69), standardized effect d = 0.06; z-test p = 0.621.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OTX-101 0.05% and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OTX-101 0.09% and the control. The interval gives the range of effects that remain compatible with the data.

Corneal Staining Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • OTX-101 0.05%: mean -1.40 versus -0.60 on control; difference -0.80 (95% CI -1.48 to -0.12), standardized effect d = -0.27; z-test p = 0.021.
  • OTX-101 0.09%: mean -1.40 versus -0.60 on control; difference -0.80 (95% CI -1.43 to -0.17), standardized effect d = -0.28; z-test p = 0.013.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for OTX-101 0.05% than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for OTX-101 0.09% than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Schirmer's Test

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • OTX-101 0.05%: mean 0.41 versus -0.08 on control; difference 0.49 (95% CI 0.19 to 0.79), standardized effect d = 0.38; z-test p = 0.001.
  • OTX-101 0.09%: mean 0.37 versus -0.08 on control; difference 0.45 (95% CI 0.15 to 0.75), standardized effect d = 0.35; z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for OTX-101 0.05% than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for OTX-101 0.09% than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover several distinct domains: tear film break-up time, corneal staining score, Schirmer's Test, and patient satisfaction. The posted numerical comparisons show a broader pattern in which some measures have estimated differences in a direction favoring a greater change in the active groups, while the tear film break-up time comparisons are less conclusive by their confidence intervals. A posted patient-satisfaction result is not included in the secondary summaries.

This pattern adds context to the primary staining result, but it is not a single unified confirmation. These outcomes measure different features, use different scales, and have different amounts of variability. Agreement in direction across measures can be informative, but it does not demonstrate that they all measure the same underlying effect. Conversely, less conclusive results on one measure do not negate a result on another.

The secondary comparisons are unadjusted in the posted summaries. When several outcomes and contrasts are examined, the chance of obtaining at least one apparently unusual result can increase. Without a reported multiplicity strategy, individual secondary p-values carry less weight as confirmatory evidence than a prespecified primary comparison would. The registry record does not give a hierarchy among the secondary measures or identify which were intended to be confirmatory.

The record lists no reported analyses for the secondary outcomes. The available group summaries and comparisons can be described, but the registry does not provide further analysis details, including any adjusted models or sensitivity analyses. These results are best treated as supporting or hypothesis-generating information rather than as independent proof of a broad effect across all measured outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Tear Film Break up Time (TBUT)
• Corneal Staining Score
• Schirmer's Test
• Patient Satisfaction

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a mean change in a numerical staining score. A mean gives the arithmetic average of the observed changes within a group. The standard deviation describes how dispersed individual observations are around that group average. These two summaries answer different questions: the mean describes the center of the group data, while the standard deviation describes variation among observations. Neither one alone tells the full shape of the outcome distribution.

What does the comparison estimate?

Each active concentration is compared with vehicle using a mean difference. The estimate is the active-group mean change minus the vehicle-group mean change, as represented in the posted comparison. A negative difference means the active-group average change is more negative than the vehicle-group average change. Because the scale's higher descriptions indicate more staining, this is a direction toward a larger average reduction in staining score, not a claim that all participants improved or that the difference is clinically important.

The registry gives the group means and comparison estimates. For example, the primary mean changes are -1.9, -1.8, and -1.2 across the two concentrations and vehicle, with comparison estimates of -0.7 and -0.6. Those estimates are accompanied by confidence intervals. The differences are not adjusted for any covariates in the summaries presented in the record; whether other adjusted analyses were carried out is not reported in the registry record.

How should the confidence intervals be read?

A confidence interval is a range of values compatible with the data and the statistical procedure, under its assumptions. Narrower intervals indicate more precise estimates; wider intervals indicate greater uncertainty. For a mean difference, an interval that includes zero is compatible with no difference under the interval procedure, while an interval entirely on one side of zero is evidence of a difference in that direction under the same procedure. This general explanation does not establish clinical importance, and the interval is not a range expected to contain every individual participant's result.

The listed primary intervals do not include zero. The corresponding p-values are explicitly unadjusted. A p-value describes how unusual data at least as incompatible with a zero-difference hypothesis would be under the assumed model; it is not the probability that the hypothesis is true, nor a measure of effect size. The record does not report adjustment for multiple comparisons, so the p-values should not be interpreted as accounting for the full set of outcomes or treatment contrasts.

What does the analysis population and carry-forward approach mean?

The primary outcome is listed for the intent-to-treat population, with last observed carried forward. Intent-to-treat generally refers to analyzing participants according to their randomized assignment, regardless of later adherence, although the exact implementation is not described in the registry record. Last observed carried forward is a missing-data approach in which a participant's last available measurement is used in place of a later missing measurement. As a general statistical matter, this approach relies on assumptions about what the missing value would have been. The record does not report the amount or pattern of missing data, or sensitivity analyses testing alternative assumptions.

The record lists standard deviations for the group outcomes. The posted comparisons use pooled standard deviations for the planning illustrations. A pooled standard deviation combines variability across two groups for the purpose of an unadjusted comparison, under assumptions appropriate to that calculation. These recalculated comparisons are simple unadjusted summaries based on posted statistics; they should not be mistaken for a fully specified trial analysis. The discrepancy indicator is false, so there is no recorded discrepancy requiring the sponsor's own analysis to take precedence.

Why can variability matter?

When outcomes are highly variable relative to a difference between group means, it is harder to estimate that difference precisely. Larger samples can generally improve precision, all else being equal. The primary score's standard deviations describe substantial variation in the score changes compared with the group mean differences, which is why the intervals and the underlying variability both matter when interpreting an average effect. This is a general statistical point, not a separate conclusion about the clinical value of the observed contrast.

The registry labels the study randomized and masked but does not report the randomization procedure, the analysis model, assumptions about the distribution of change scores, handling of repeated measurements, or a protocol-specific adjustment strategy. Those details are not reported in the registry record. Without them, the posted numerical summaries can be interpreted, but the precise analysis specification cannot be reconstructed.

11. Confidence Intervals and Precision

The primary comparison intervals are -1.189 to -0.211 for OTX-101 0.05% versus vehicle and -1.099 to -0.101 for OTX-101 0.09% versus vehicle. Both lie below zero, matching the negative direction of the estimated mean differences. The intervals indicate uncertainty around the group-level estimates: the precise magnitude is not known, even though the listed ranges are on the same side of zero.

These intervals do not describe the spread of individual participant results. The group standard deviations, 2.17 for OTX-101 0.05%, 2.27 for OTX-101 0.09%, and 2.17 for vehicle, describe variation in the observed changes. An interval around a mean difference answers a different question: how precisely the between-group contrast is estimated from the available data.

Precision should not be confused with clinical relevance. The registry record does not state a threshold for a meaningful change in staining score, so the interval cannot be classified against such a threshold from the record alone. Nor does an interval fully capture possible uncertainty from missing-data assumptions, analysis choices, or multiple comparisons. The confidence intervals are useful summaries of statistical uncertainty under their calculation, but they are not a substitute for those unreported details.

For the secondary outcomes, the intervals vary in whether they include zero. This illustrates that precision and direction can differ across measures. The registry record does not report a multiplicity adjustment for these comparisons, and the intervals should be read as individual comparisons rather than as a family-wise guarantee across all outcomes.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the original trial's design assumptions. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. For these continuous outcomes, the figures are participants per arm, not total events.

The 80% power column gives the planned number of participants per arm that the calculation estimates would be needed to have an 80% chance of detecting the chosen effect under those assumptions, if that effect and the model assumptions held. The 90% power column uses a higher chance of detection and therefore generally requires more participants per arm. The figures are not a statement about how much power the completed trial actually had.

Each planning row uses a different fraction of the observed effect. Planning for 75% of the observed effect or 50% of the observed effect means targeting a smaller difference than the full observed estimate. Smaller effects are harder to detect and require more participants per arm under the calculation assumptions. The figures can therefore change substantially across the rows, especially when the observed comparison is small relative to variability.

This is not observed power. It is a forward-looking illustration that reuses the observed effect estimate as an input; it does not establish the probability that the trial's findings are true. The original sample-size justification, target effect, allowance for loss to follow-up, and trial-specific power assumptions are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.700; pooled standard deviation σ = 2.170.
2. n = 2 × (1.96 + 0.842)² × 2.170² / -0.700² = 150.9, rounded up to 151 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.7                      # observed difference in means
sigma <- 2.17                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2254265)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 151 (80% power), 202 (90% power)
 75% of observed effect: n per arm = 269 (80% power), 360 (90% power)
 50% of observed effect: n per arm = 604 (80% power), 808 (90% power)
power.t.test: 151.8 
Simulated power at n = 151 per arm: 0.801 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and multiple secondary outcomes, with comparisons of each OTX-101 concentration against vehicle. The primary comparisons have unadjusted p-values. No multiplicity adjustment or testing hierarchy is reported in the registry record. When multiple outcomes or contrasts are tested, the chance of at least one nominally small p-value can increase. This is a general statistical concern; it does not mean that any particular reported result is false. It does mean that unadjusted results should be interpreted as individual comparisons rather than as a controlled family of tests.

The record specifies the intent-to-treat population and last observed carried forward approach for the primary outcome. It does not report the number of missing primary measurements, reasons for missingness, or the timing of missing observations. It also does not describe sensitivity analyses under alternative missing-data assumptions. Carrying forward a participant's last observation may not represent what would have been measured later, especially if the outcome could change over time. The impact cannot be quantified from the registry record.

The exact analysis population and missing-data handling for each secondary measure are not reported in the registry record. Nor are details of the randomization sequence, allocation concealment, analysis model, covariate adjustment, or protocol deviations. These omissions limit assessment of how closely the posted summaries follow the trial's planned analysis.

The registry gives a primary endpoint timeframe and a stated analysis approach, but it does not report a complete statistical analysis plan or the original sample-size justification. It also lists no reported analyses for the secondary outcomes. As a result, it is not possible to determine from the record whether additional planned tests, sensitivity analyses, or multiplicity controls were performed elsewhere.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: peripheral nerve decompression (0.7%), hypokalaemia (0.7%), humerus fracture (0.7%), cerebrovascular accident (0.7%), bipolar disorder (0.7%).

The registry reports serious adverse event counts among participants at risk: 1 for OTX-101 0.09%, 0 for OTX-101 0.05%, and 4 for vehicle. No deaths are listed in any group. The five serious-event terms listed at 0.7% each are peripheral nerve decompression, hypokalaemia, humerus fracture, cerebrovascular accident, and bipolar disorder. These are reported terms, not evidence that every event was caused by the assigned treatment.

The registry also reports participants affected by other adverse events: 37 for OTX-101 0.09%, 31 for OTX-101 0.05%, and 30 for vehicle. These counts should be read separately from the serious-event counts. They are counts of affected participants in the listed groups, not a measure of event severity or causal relationship.

Safety counts are descriptive. The record does not provide event-level timing, duration, recurrence, attribution, or comparative statistical analyses. The figures therefore do not establish whether group differences are meaningful, and they cannot rule out uncommon harms or events not captured in the record.

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

The posted primary results show lower mean staining-score changes in both OTX-101 groups than in the vehicle group, with mean differences of -0.7 and -0.6. The listed intervals for those contrasts are below zero. In the context of the score descriptions, the estimates point toward a greater average reduction in staining score for the active groups over the stated baseline-to-day-84 timeframe.

That is a description of the recorded group averages, not an individual prediction. The data do not imply that every participant had the same experience, and the standard deviations indicate that observed changes varied within groups. The record also does not identify a threshold for a change that participants would consider important, so statistical evidence for a difference cannot on its own answer whether the size matters in practice.

The findings are limited to the measured outcome, the listed population, and the 84-day treatment regimen. The results do not establish longer-term effects, effects on outcomes not measured, or effects in populations not represented in the record. The secondary summaries add information across other outcome domains, but they are not a substitute for the primary result and have no reported multiplicity adjustment.

Safety counts likewise require cautious interpretation. Serious and other adverse events are listed descriptively, without enough information to determine causation or provide a full comparative safety assessment. The registry record does not report detailed analysis methods, missing-data patterns, or a clinical-importance threshold for the primary score.

In short, the record supports a statistical description of the posted group comparisons, with intervals that quantify some uncertainty under their calculation. It does not establish a comprehensive benefit-risk conclusion or resolve the importance of the observed score differences.

17. Why This Trial Matters Statistically

This trial illustrates why a clinical result should be read through several statistical lenses. The primary estimates describe the direction and size of average group differences, the confidence intervals describe precision, and the standard deviations show that individual score changes vary. No one of these summaries is sufficient alone.

It also illustrates the distinction between statistical evidence and clinical importance. The primary intervals lie below zero, but the registry record does not specify a meaningful-change threshold for the score. A statistically distinguishable average difference is not automatically a difference that patients would notice or value. Such interpretation requires clinical context that is not included in the record.

The dose-ranging design offers two active concentrations against a common vehicle group, but the posted comparisons do not establish a dose-response pattern by themselves. The estimated differences are close in direction and size, and the registry record does not report a formal comparison between the two active concentrations. The evidence should therefore be read as two active-versus-vehicle comparisons, not as a demonstrated ranking of concentrations.

Finally, the record highlights the importance of prespecified analysis plans. Multiple outcomes and contrasts, missing-data assumptions, and the definition of analysis populations can affect interpretation. Here, the primary population and carry-forward approach are named, but multiplicity procedures, the original sample-size assumptions, and several analysis details are not reported. These gaps matter when judging how strongly the numerical summaries support broader conclusions.

18. 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.

Several trial-specific limitations are apparent from the registry record. The treatment and primary outcome timeframe is 84 days, so the posted endpoint does not describe longer-term outcomes. The primary measure is a score on a scale, and the record does not identify a clinically important difference or explain how a given change relates to patient experience.

The primary outcome uses last observed carried forward, but the record does not report the extent or pattern of missing data or sensitivity analyses. This leaves uncertainty about how missing measurements may affect the group estimates. Details of the randomization method, allocation concealment, masking procedures, and analysis model are also not reported in the registry record.

The comparisons are listed with unadjusted p-values, and the record does not describe a multiplicity strategy despite several secondary outcomes and treatment contrasts. The registry lists no reported secondary analyses. Patient satisfaction is named as a secondary outcome, but its numerical results are not included in the posted secondary summaries.

Finally, the original sample-size justification and trial-specific design assumptions are not reported. The planning illustrations based on observed effects do not replace that missing design rationale. These limitations do not invalidate the posted summaries, but they constrain conclusions about robustness, clinical importance, and how the results relate to the full set of outcomes examined.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Phase 2/3 Dose-Ranging Study of the Safety and Efficacy of OTX-101 in the Treatment of Keratoconjunctivitis Sicca — NCT02254265.
• Registry record last updated 2022-08-29; 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.

22. Record Summary

NCT02254265 is a completed randomized, multicenter, double-masked, vehicle-controlled Phase 2/3 dose-ranging study of OTX-101 for keratoconjunctivitis sicca. The parallel-group trial lists OTX-101 0.05%, OTX-101 0.09%, and vehicle, each dosed in both eyes twice daily for 84 days.

The primary outcome is mean change from baseline to day 84 in lissamine green conjunctival staining score for the designated study eye. The posted mean differences versus vehicle are -0.7 for OTX-101 0.05% and -0.6 for OTX-101 0.09%; both listed confidence intervals lie below zero. The record specifies intent-to-treat analysis with last observed carried forward for this outcome.

Secondary outcomes cover tear film break-up time, corneal staining score, Schirmer's Test, and patient satisfaction. Unadjusted comparisons and descriptive adverse event counts are available, while multiplicity procedures, the original sample-size justification, and several analysis details are not reported in the registry record.