Safety and Tolerability of PRO-087 Versus Xyel Ofteno® and Systane Ultra®, on the Ocular Surface of Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability of PRO-087 Versus Xyel Ofteno® and Systane Ultra®, on the Ocular Surface of Healthy Subjects (NCT03524157), a randomized phase 1 study. The primary outcome is Goblet Cell Density (GCD).

2. Clinical Question

This was a Phase I randomized parallel-group study with 30 participants enrolled. Its stated objective was to evaluate the safety and tolerability of PRO-087 on the ocular surface of clinically healthy subjects, with Xyel Ofteno and Systane Ultra as comparators. The hypothesis in the study description was that PRO-087 would have a safety and tolerability profile similar to the comparators.

The primary endpoint was goblet cell density measured at the end of treatment. The record reports group means and standard deviations, a Kruskal-Wallis analysis across the groups, and a recalculated pairwise comparison of PRO-087 with Xyel Ofteno. These are different summaries of the data and address the results in different ways. The posted record does not report a corresponding pairwise comparison with Systane Ultra.

Interpretation is limited by the small group sizes, the short treatment period, and the fact that the study enrolled healthy subjects. The results describe measurements in this study; they do not establish what would happen in people with an ocular condition. Details such as the original sample-size justification, non-inferiority margin, and full analysis plan are not reported in the registry record.

3. Trial Design

The registry identifies this as a Phase I randomized, parallel-group study with triple masking. The brief study description calls it controlled, parallel, randomized, and exploratory, and describes it as double blind. The difference between the registry masking classification and the brief-description wording is present in the record; which people were masked is not reported in the registry record.

The study compared three groups: PRO-087, Xyel Ofteno, and Systane Ultra. Each arm description specifies one drop in both eyes four times a day during the waking period for 10 days. The PRO-087 formulation is described as preservative-free. Xyel Ofteno and Systane Ultra have different listed active ingredients and product descriptions. The study began on 2017-07-17, reached primary completion on 2018-02-12, and is listed as completed.

The registry reports an enrollment of 30. For the primary goblet cell density outcome, the posted group summaries include 10 participants for PRO-087, 10 for Xyel Ofteno, and 9 for Systane Ultra. The reason the primary outcome summary has 9 participants in the Systane Ultra group is not reported in the registry record. It also does not explain whether the endpoint analysis used an intention-to-treat, per-protocol, or another analysis population.

The study description identifies the trial as exploratory and says it evaluated safety and tolerability in clinically healthy subjects. Although the primary analysis is labelled non-inferiority, the registry record does not report the margin, the planned statistical test, or the criteria used to reach a non-inferiority conclusion. Nor does it report the original sample-size justification or details about interim analyses. Those omissions matter when assessing whether a small study was designed to support a formal non-inferiority claim.

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

Reasons for not completing this period:

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: Clinical and ophthalmologically healthy subjects who met the inclusion criteria

6. Primary Endpoint

The registry lists the primary outcome as Goblet Cell Density (GCD), measured over will be evaluated at the end of the treatment at the final visit (day 10).

The primary endpoint is goblet cell density, abbreviated GCD, measured in cells/mm2 by impression cytology at the final visit on day 10. Goblet cells are cells on the ocular surface; the registry describes their density as a continuous measure and reports group means with standard deviations. The record states that the normal value is higher than 500 cells per square millimeter.

A continuous endpoint preserves information about the measured quantity across participants rather than reducing it to a simple yes-or-no category. Group means describe the average observed density, while standard deviations describe how spread out the individual measurements are within each group. Neither summary alone shows the full distribution of participant values.

The measure was chosen as an assessment of the ocular surface in a study whose stated objective was safety and tolerability. It can provide a numerical comparison across treatment groups at the end of the 10-day treatment period. The registry does not explain why this endpoint was selected as primary, how it relates to the study’s safety hypothesis, or whether the day 10 measurement was chosen for a specific biological or clinical reason.

The posted means were 282.5 for PRO-087, 326.8 for Xyel Ofteno, and 291.5 for Systane Ultra. Each is below the registry’s stated normal-value description of higher than 500. This comparison is descriptive only: the record does not provide participant-level data, a reference-group analysis, or an explanation of how the stated normal value should be used to interpret a treatment comparison. The endpoint therefore needs to be read alongside the uncertainty in the group comparisons and the limits of the study design.

7. Results Posted in the Registry

• Xyel Ofteno: mean 326.80 versus 282.50 on control; difference 44.30 (95% CI -47.69 to 136.29), standardized effect d = 0.42; z-test p = 0.345.

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.

Intraocular Pressure (IOP)

• 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:
  • Xyel Ofteno: mean 12.55 versus 12.80 on control; difference -0.25 (95% CI -2.02 to 1.52), standardized effect d = -0.12; z-test p = 0.782.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Xyel Ofteno and the control. The interval gives the range of effects that remain compatible with the data.

Breakup Time (BUT)

• 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:
  • Xyel Ofteno: mean 7.30 versus 8.80 on control; difference -1.50 (95% CI -3.34 to 0.34), standardized effect d = -0.71; z-test p = 0.110.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Xyel Ofteno and the control. The interval gives the range of effects that remain compatible with the data.

The listed secondary outcomes span safety events and several ocular measurements, including intraocular pressure, epithelial defects, breakup time, conjunctival hyperemia, chemosis, ocular burning, and foreign body sensation. The posted secondary summaries shown in the tables should be read as supporting context, not as substitutes for the primary endpoint. The registry’s objective emphasizes safety and tolerability, while the primary endpoint is goblet cell density.

For the secondary analyses with detailed results, the record includes group summaries and a recalculated pairwise comparison for intraocular pressure, and group summaries, a pairwise recalculation, and a reported overall Kruskal-Wallis result for breakup time. The numerical results and intervals are presented in the tables; they should be interpreted with the same care as the primary comparison. Other listed secondary measures do not have detailed numerical findings in the registry record available for this analysis.

The secondary findings do not change the primary result, which remains an overall reported analysis and a separate pairwise recalculation with limited precision. Secondary endpoints can help describe patterns across aspects of ocular status, but multiple outcomes create more opportunities for apparently notable results to arise by chance. The record does not report whether secondary analyses were prespecified, how many comparisons were planned, or whether any adjustment for multiple testing was used.

For that reason, unadjusted secondary results carry less weight than a clearly specified primary analysis, especially in an exploratory study with several outcomes. A secondary p-value should not be treated as confirmatory evidence in isolation. The appropriate reading considers the outcome’s role, the estimate and uncertainty, whether the analysis was planned, and whether a multiplicity strategy was used; those planning details are not reported in the registry record.

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

• Presence of Adverse Events (AEs)
• Intraocular Pressure (IOP)
• Epithelial Defects (ED)
• Breakup Time (BUT)
• Conjunctival Hyperemia (CH)
• Chemosis
• Ocular Burning (OB)
• Foreign Body Sensation (FBS)

9. Statistical Interpretation

10. Statistical Methods Explained

The posted results combine a sponsor-reported analysis with summary statistics that allow a simple unadjusted recalculation for selected comparisons. These methods answer related but distinct questions. The reported method for the primary endpoint is Kruskal-Wallis across three groups. The recalculated comparison of PRO-087 with Xyel Ofteno is expressed as a mean difference with a confidence interval and an unadjusted p-value. Neither should be mistaken for the other.

What does a group mean describe?

For a continuous measure such as goblet cell density, the mean summarizes the average observed value in a group. The standard deviation describes the dispersion of participant measurements around that group mean. A mean difference compares the averages of two groups; the sign depends on the order of subtraction used in the reported comparison. In the posted primary comparison, the mean difference is 44.3 cells/mm2 for Xyel Ofteno relative to PRO-087. The estimate is a summary of this sample, not a guarantee about the difference that would be seen in a larger or different population.

Means and standard deviations are useful summaries, but do not show whether values are skewed, whether there are unusual observations, or how individual participant measurements relate across visits. Participant-level values and distribution plots are not reported in the registry record. The registry reports an overall Kruskal-Wallis analysis, a rank-based method that compares group distributions rather than directly testing a difference in means. That distinction helps explain why the sponsor-reported overall analysis and a summary-based pairwise mean comparison are not identical analyses.

How should the Kruskal-Wallis result be read?

The Kruskal-Wallis test is an omnibus, or overall, comparison of groups. Here it is reported for all three groups. Its p-value of 0.273 does not quantify the size of a treatment difference, and it does not say which pair of groups differs. A p-value describes how unusual the observed data, or data more extreme, would be under the test’s null model. It is not the probability that the null hypothesis is true, and it does not establish that groups are equivalent when it is not small.

The registry labels this analysis as non-inferiority, but a non-inferiority assessment depends on a prespecified margin and a decision rule. The margin defines how much worse an intervention could be while still meeting the non-inferiority objective. The margin and the sponsor’s detailed analysis procedure are not reported in the registry record. Without them, the reported Kruskal-Wallis p-value cannot independently establish whether a non-inferiority criterion was met.

What does the recalculated comparison add?

The recalculated pairwise result focuses on PRO-087 and Xyel Ofteno. It reports a mean difference of 44.3 cells/mm2 and a 95% confidence interval from -47.69 to 136.3, with an unadjusted p-value of 0.345. This provides an estimate of the size and uncertainty of one pairwise mean contrast. It is unadjusted, so it should not be read as accounting for multiple comparisons or for a prespecified analysis plan. The registry also reports an overall three-group test, which has a different scope from this two-group contrast.

A confidence interval gives a range of values compatible with the data under the method used and its assumptions. A wide interval indicates limited precision. An interval spanning zero means the data do not rule out no mean difference at the conventional two-sided level, but it also does not establish equivalence. A formal equivalence or non-inferiority conclusion requires its own defined margin and analysis procedure; neither can be reconstructed from the interval alone.

Why can over-dispersion matter?

General statistical explanation: when measurements vary substantially within groups, the uncertainty around a group comparison tends to be larger than it would be with less variation, all else equal. In clinical data, variability can arise from differences between participants, measurement variation, or other sources. Standard deviations help describe this spread. The primary endpoint standard deviations vary across the three groups, and the group sizes are small, so the mean estimates and their contrasts should be interpreted with attention to uncertainty. The record does not provide individual measurements or diagnostics that would allow a fuller assessment of distributional assumptions.

Rank-based methods can be useful when a mean-based model’s assumptions are doubtful, but the registry does not give the rationale for selecting Kruskal-Wallis or describe checks of assumptions. A rank-based test does not automatically answer a question about equality of means or prove non-inferiority. The estimand, endpoint scale, and test need to be considered together.

What is the role of p-values?

A p-value is a measure of compatibility between the data and a particular null hypothesis under the chosen model. It is not a measure of clinical importance, precision, or the probability that a treatment works. The primary overall p-value and the recalculated pairwise p-value address different comparisons. The pairwise p-value is explicitly unadjusted; multiplicity procedures are not reported in the registry record. P-values should therefore be read together with the effect estimate, interval, design, and analysis details rather than used as standalone conclusions.

General statistical explanation: confidence intervals and p-values are closely related when they arise from the same model and hypothesis, but the reported overall test and the recalculated pairwise comparison are not the same test. They need not yield matching values. The record does not describe the sponsor’s complete statistical plan, so it is not possible to determine from the registry alone which additional analyses were planned, whether any were prespecified, or how secondary comparisons were handled.

11. Confidence Intervals and Precision

The primary pairwise recalculation is accompanied by a 95% confidence interval from -47.69 to 136.3 cells/mm2 for the mean difference between Xyel Ofteno and PRO-087. The interval includes zero, so the posted summary data are compatible with no mean difference under the method used. It also includes values in either direction, so it does not establish the direction of the underlying difference with precision.

The interval is wide relative to the point estimate. This reflects the limited precision of the comparison, in the context of small groups and variability in the outcome. The standard deviations reported for the primary endpoint are 78.6 for PRO-087, 125.9 for Xyel Ofteno, and 135.3 for Systane Ultra. The interval should not be read as covering every possible true value with certainty; it is a model-based range with a stated confidence level.

A confidence interval is not a probability statement that the true difference lies within this particular interval. Rather, in general, the procedure used to construct intervals has a stated long-run coverage under its assumptions. Here, the exact assumptions and procedure behind the recalculated interval are not described in the registry record beyond the summary-based recalculation. Participant-level data are not available in the record to assess the distribution or independently verify the interval.

Most importantly, the interval is not a non-inferiority interval in the absence of a reported margin and prespecified decision rule. It cannot demonstrate equivalence merely because it includes zero. The overall Kruskal-Wallis result does not supply a pairwise confidence interval. The posted results therefore offer limited precision for the primary pairwise contrast and do not fully specify the uncertainty relevant to a formal non-inferiority conclusion.

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 section is a planning illustration based on the observed effect in the recalculated comparison of PRO-087 and Xyel Ofteno. The figures are participants per arm, not total participants and not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect.

The 80% power column gives the number of participants per arm in the illustration for an 80% chance of detecting the specified effect under those assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding number per arm for a 90% chance. These are hypothetical planning quantities, not counts observed in this trial. This is not observed power.

The table shows planning values for detecting 100%, 75%, and 50% of the observed effect. Smaller target effects generally require more participants because a smaller signal is harder to distinguish from variability. The figures are tied to the observed effect in a small study, so they should not be treated as a definitive design recommendation. In particular, the original trial’s sample-size justification and design assumptions are not reported in the registry record.

The sample-size illustration covers the PRO-087 versus Xyel Ofteno comparison. It does not describe a three-arm non-inferiority design, and the record does not report a non-inferiority margin that could be used to plan such a study. The table and curve are most useful for showing how sample requirements change under the listed assumptions, not for reconstructing the trial’s original planning or proving whether the completed trial had adequate power.

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 = 44.300; pooled standard deviation σ = 104.949.
2. n = 2 × (1.96 + 0.842)² × 104.949² / 44.300² = 88.1, rounded up to 89 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 <- 44.3                      # observed difference in means
sigma <- 104.949440208131                     # 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(3524157)
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 = 89 (80% power), 118 (90% power)
 75% of observed effect: n per arm = 157 (80% power), 210 (90% power)
 50% of observed effect: n per arm = 353 (80% power), 472 (90% power)
power.t.test: 89.1 
Simulated power at n = 89 per arm: 0.803 (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. Analyses Reported by the Sponsor

The registry reports a sponsor analysis of the primary endpoint using a Kruskal-Wallis test across PRO-087, Xyel Ofteno, and Systane Ultra, with p = 0.273. It labels this result as non-inferiority. The posted recalculation is a separate, unadjusted comparison of the PRO-087 and Xyel Ofteno group means, with a mean difference of 44.3 cells/mm2, a 95% confidence interval from -47.69 to 136.3, and p = 0.345.

These results should not be treated as competing estimates of the same test. The sponsor’s analysis is an overall rank-based comparison across three groups; the recalculation is a pairwise mean comparison for two groups. They differ in both the groups included and the statistical quantity assessed. The registry does not report enough detail about the sponsor’s non-inferiority procedure to determine how the test relates to a margin or what decision rule was used.

The record does not flag a discrepancy between the posted and recalculated results. Even so, the sponsor-reported analysis is the study’s reported analysis, while the recalculation is a simple unadjusted analysis of summary statistics. Neither alone resolves the missing information about the non-inferiority margin, analysis population, multiplicity handling, or prespecified plan. The sponsor’s result should be described as reported, not extended beyond the details available in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The study includes a primary endpoint, multiple secondary outcomes, three randomized groups, and at least one overall analysis and pairwise recalculation. When a study examines multiple outcomes or comparisons, the chance of obtaining one apparently notable result can increase if each test is considered separately. Statistical plans often address this by identifying a primary comparison, specifying how secondary analyses will be interpreted, or using a multiplicity adjustment. The registry record does not report whether an adjustment was planned or applied.

The primary analysis is reported as a Kruskal-Wallis test across three groups, while the posted recalculation is an unadjusted pairwise mean comparison of PRO-087 and Xyel Ofteno. It is not reported whether that pairwise contrast was prespecified, whether other pairwise comparisons were planned, or how these analyses fit into the sponsor’s complete testing hierarchy. The word unadjusted describes the recalculated p-value; it does not establish what adjustment, if any, was used for the sponsor’s analysis.

The record also does not report the non-inferiority margin or the detailed decision rule for the labelled primary non-inferiority analysis. Without a margin, the reader cannot assess what degree of difference would have been considered acceptable. The registry does not provide a statistical analysis plan that would clarify the estimand, hypotheses, test assumptions, or handling of secondary outcomes.

Missing-data methods and analysis populations are also not described. Although 30 participants were enrolled, the primary outcome summaries show 10 participants in PRO-087, 10 in Xyel Ofteno, and 9 in Systane Ultra. The reason for the difference between enrollment and the available primary summary is not reported in the registry record. It is not reported whether missing observations were imputed, excluded, or handled in another way, or whether safety and efficacy populations differed.

These gaps do not show that the analyses were inappropriate; they limit what can be verified from the registry. A fuller assessment would require the prespecified analysis plan, the non-inferiority margin, the participant flow and analysis populations, and the methods used for missing observations and multiplicity.

16. 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 non-serious adverse event terms

The posted serious adverse event summaries report 0 serious events affecting participants in each arm, with 10 participants at risk in each arm. The record also reports 0 deaths in each group. These are counts during the study as represented in the registry; they do not establish that serious events cannot occur or that the groups have identical safety profiles.

The registry separately reports other adverse events affecting 5 of 10 participants in the PRO-087 group, 4 of 10 in the Xyel Ofteno group, and 5 of 10 in the Systane Ultra group. Those are not serious-event counts, and they should not be conflated with the serious adverse event figures. The registry does not provide serious-event terms, and its list of top serious-event terms is empty.

Safety interpretation is constrained by the small group sizes and 10-day treatment period. A lack of recorded serious events in this study is a description of what was observed, not evidence that rare or longer-term harms are absent. The record does not provide additional detail about event severity, relatedness, timing, or how events were adjudicated. These summaries should therefore be read as limited descriptive safety information from this trial.

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

This trial provides a small, short-term comparison of PRO-087 with Xyel Ofteno and Systane Ultra in clinically healthy subjects. It reports day 10 group summaries for goblet cell density, an overall Kruskal-Wallis analysis labelled as non-inferiority, and adverse-event counts. The primary pairwise recalculation for PRO-087 versus Xyel Ofteno has a broad confidence interval that includes zero and values on either side. The results describe the observed sample; they do not settle the size or direction of a population difference.

The record’s non-inferiority label should be interpreted cautiously because the margin and decision rule are not reported. A non-significant result is not the same as evidence of equivalence, and a study cannot demonstrate non-inferiority from a p-value label alone without the relevant margin and analysis details. Likewise, the observed means do not establish a clinically meaningful benefit or harm.

The results also do not establish what would occur in people with dry eye or another ocular condition. The study objective and population description concern healthy subjects, and the treatment period was 10 days. The registry does not report a longer follow-up period or outcomes that would support conclusions beyond the measurements and events recorded in the study.

For safety, the record reports no serious adverse events or deaths during the study, alongside counts for other adverse events. These observations are reassuring only as a description of the limited trial experience; the small groups and short duration cannot rule out uncommon or later events. No medical recommendation follows from these data. The useful conclusion is narrower: the registry offers an exploratory snapshot of measured ocular outcomes and safety events, with substantial uncertainty and important design details not reported.

18. Why This Trial Matters Statistically

Statistically, this study illustrates why the design label, endpoint, reported test, and intended claim need to be read together. The primary endpoint is continuous goblet cell density, but the reported sponsor analysis is a rank-based overall test across three groups and is labelled non-inferiority. A separate recalculation gives a pairwise mean difference for two groups. Those analyses answer different questions, and the registry does not report the margin needed to evaluate the non-inferiority claim.

The small group sizes make precision central to interpretation. The pairwise confidence interval spans values in either direction, so the point estimate alone cannot give a stable account of the underlying difference. This makes the study useful as an example of why statistical uncertainty matters even when group means and p-values are available.

The record also demonstrates the importance of transparency around analysis populations, missing observations, multiplicity, and sample-size planning. Enrollment is reported, but the primary outcome summary has a different number for one arm, and the reason is not given. Several secondary outcomes are listed, while adjustment and prespecification details are not reported. Those gaps restrict reproducibility and the strength of conclusions, without showing that the underlying work was necessarily flawed.

Finally, the trial’s exploratory Phase I context and healthy-subject population set clear boundaries on what the results can address. The data can be described, compared, and used to illustrate planning assumptions, but they do not resolve the clinical implications of the formulations or establish a formal non-inferiority conclusion from the registry information alone.

19. 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 limitations specific to this trial affect how confidently the posted results can be interpreted. The primary outcome summaries include only 10 participants in the PRO-087 group, 10 in the Xyel Ofteno group, and 9 in the Systane Ultra group. The registry reports 30 participants enrolled but does not explain the smaller primary outcome count for Systane Ultra or how any unavailable measurements were handled.

The study lasted 10 days, and the primary endpoint was measured at the final visit. Longer-term outcomes are not reported in the registry record. The study description focuses on clinically healthy subjects, which limits the population to which these observations can be applied. The listed conditions should not be taken to mean that participants with those conditions were enrolled.

The primary analysis is labelled non-inferiority, but the margin, detailed statistical procedure, and decision rule are not reported. The record also does not report the original sample-size justification, the analysis populations, the handling of missing data, or whether secondary analyses were adjusted for multiple comparisons. These omissions make it difficult to assess the intended design and reproduce the sponsor’s analysis.

The registry classifies masking as triple, while the brief methodology describes the study as double blind. It does not specify which study roles were masked. This difference in wording leaves the masking procedures unclear. Finally, the posted numerical summaries do not include individual participant data or a full distributional assessment, limiting independent evaluation of assumptions and outlying observations.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Tolerability of PRO-087 Versus Xyel Ofteno® and Systane Ultra®, on the Ocular Surface of Healthy Subjects — NCT03524157.
• Registry record last updated 2019-07-19; status last verified 2019-05.
• Results first posted 2019-07-19.
• 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.

23. Record Summary

This completed randomized Phase I parallel-group study compared PRO-087, Xyel Ofteno, and Systane Ultra in clinically healthy subjects. The registry reports 30 participants enrolled and a 10-day regimen for each arm. Its primary endpoint was goblet cell density at the day 10 visit.

The sponsor-reported primary analysis was a three-group Kruskal-Wallis test with p = 0.273, labelled non-inferiority. A separate recalculation comparing PRO-087 with Xyel Ofteno gives a mean difference of 44.3 cells/mm2 and a 95% confidence interval from -47.69 to 136.3. The registry does not report a non-inferiority margin, detailed analysis plan, or reason for the Systane Ultra primary summary having 9 participants.

The serious adverse event summary lists 0 events in each group, and the record reports 0 deaths. The small groups, short duration, and unreported analysis details limit what can be concluded from these results.