Phase 1/2a Safety and Efficacy of ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1/2a Safety and Efficacy of ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease (NCT04201574), a randomized phase 1, phase 2 study. The primary outcome is Number of Subjects With Adverse Events.

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, vehicle-controlled Phase 1/2a study with a parallel-group model. The official title describes evaluation of safety and exploratory activity for two concentrations of ALY688 ophthalmic solution in subjects with dry eye disease. The registry lists quadruple masking. It does not explain which study roles were masked, so the specific masking arrangement is not reported in the registry record.

Enrollment was 138. The posted primary outcome includes 46 participants in each arm: Vehicle Ophthalmic Solution, ALY688 Ophthalmic Solution 0.1%, and ALY688 Ophthalmic Solution 0.4%. The registry status is completed. The recorded start date is 2019-12-16, and the primary completion date is 2020-09-15.

The primary outcome concerns treatment-emergent adverse events in the Safety Population over 8 weeks. The registry also lists six secondary outcome types: ocular discomfort measured by visual analog scale, Symptom Assessment in Dry Eye (SAnDE), conjunctival Lissamine Green staining, conjunctival hyperemia grading, Tear Film Break-up Time (TBUT), and Schirmer's Test. Quantitative results are posted for ocular discomfort, SAnDE, and TBUT. Numerical results for the other listed secondary outcomes are not reported in the registry record.

The registry record does not report the original sample-size justification, target effect, or design assumptions. The planning illustrations associated with the posted results use explicit assumptions, but they should not be read as the study's original design plan.

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: Safety Population

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: mITT Population

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Adverse Events, measured over 8 weeks.

The primary endpoint counts participants reporting any treatment-emergent adverse event during 8 weeks. It is reported as a count of participants, rather than as an average symptom score or a measure of time until an event. The registry identifies the analysis population as the Safety Population.

Counting participants with at least one event is a direct way to summarize how many people experienced an event during the specified observation period. It is not the same as counting the total number of events: a participant with more than one event remains one participant in this endpoint. Nor does this endpoint, by itself, describe event severity, duration, or whether an event was judged related to treatment.

The posted counts were 13 participants in the vehicle arm, 15 in the 0.1% arm, and 10 in the 0.4% arm. The registry describes the endpoint as subjects reporting any treatment-emergent adverse events. Details of the event definitions, ascertainment procedures, and adjudication are not reported in the registry record.

Safety outcomes are especially relevant in an early-phase study that evaluates different concentrations and exploratory activity. This endpoint focuses on the occurrence of adverse events during the reported timeframe. It does not establish whether an intervention is safe in other populations, over other durations, or for outcomes not captured in the record.

7. Results Posted in the Registry

• ALY688 Ophthalmic Solution 0.1%: 32.6% (15/46) versus 28.3% (13/46) on control; risk difference 4.3 percentage points (95% CI -14.4 to 23.1), risk ratio 1.15 (0.62–2.15); unadjusted two-proportion z-test p = 0.650.
• ALY688 Ophthalmic Solution 0.4%: 21.7% (10/46) versus 28.3% (13/46) on control; risk difference -6.5 percentage points (95% CI -24.2 to 11.1), risk ratio 0.77 (0.38–1.57); unadjusted two-proportion z-test p = 0.470.

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.

Ocular Discomfort Score by Visual Analog Scale

• 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:
  • ALY688 Ophthalmic Solution 0.1%: mean -4.47 versus -8.19 on control; difference 3.72 (95% CI -3.15 to 10.59), standardized effect d = 0.22; z-test p = 0.289.
  • ALY688 Ophthalmic Solution 0.4%: mean -8.62 versus -8.19 on control; difference -0.43 (95% CI -8.80 to 7.94), standardized effect d = -0.02; z-test p = 0.920.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ALY688 Ophthalmic Solution 0.1% 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 ALY688 Ophthalmic Solution 0.4% and the control. The interval gives the range of effects that remain compatible with the data.

Symptom Assessment in Dry Eye (SAnDE) Score Assessment

• 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:
  • ALY688 Ophthalmic Solution 0.1%: mean -6.76 versus -13.76 on control; difference 7.00 (95% CI -0.39 to 14.39), standardized effect d = 0.39; z-test p = 0.063.
  • ALY688 Ophthalmic Solution 0.4%: mean -15.48 versus -13.76 on control; difference -1.72 (95% CI -10.89 to 7.45), standardized effect d = -0.08; z-test p = 0.713.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ALY688 Ophthalmic Solution 0.1% 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 ALY688 Ophthalmic Solution 0.4% and the control. The interval gives the range of effects that remain compatible with the data.

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 errors.
• Result:
  • ALY688 Ophthalmic Solution 0.1%: mean 0.13 versus 0.29 on control; difference -0.16 (95% CI -0.87 to 0.55), standardized effect d = -0.09; z-test p = 0.657.
  • ALY688 Ophthalmic Solution 0.4%: mean 0.18 versus 0.29 on control; difference -0.11 (95% CI -0.83 to 0.61), standardized effect d = -0.06; z-test p = 0.765.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ALY688 Ophthalmic Solution 0.1% 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 ALY688 Ophthalmic Solution 0.4% and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover symptoms and clinical measures related to dry eye disease. The registry lists ocular discomfort, SAnDE, conjunctival Lissamine Green staining, conjunctival hyperemia grading, TBUT, and Schirmer's Test. Numerical summaries and comparison estimates are posted for ocular discomfort, SAnDE, and TBUT; quantitative results for the other listed measures are not reported in the registry record.

Across the continuous outcomes with posted comparison estimates, the point estimates vary in direction and the confidence intervals include zero. This overall pattern is not a consistent separation between either ALY688 concentration and vehicle across all measures. The estimates are uncertain, so the pattern should not be read as demonstrating that the groups are the same or that a meaningful difference is present.

These exploratory outcomes complement the primary safety endpoint but address different questions. Symptom scores and tear-film measures concern clinical activity, whereas the primary endpoint counts participants reporting adverse events. A pattern in the secondary measures cannot resolve uncertainty in the safety comparison, and the safety counts do not establish an effect on symptoms or tear-film outcomes.

The comparisons are unadjusted, and the registry record does not report a multiplicity strategy or sponsor-reported analyses. General explanation: if many outcomes are examined, some estimates may appear more pronounced by chance alone. Without a reported plan for controlling or interpreting multiple comparisons, individual secondary p-values and estimates carry less weight than a prespecified, independently confirmed result. The record's description of the activity assessment as exploratory is consistent with cautious, hypothesis-generating interpretation.

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

• Ocular Discomfort Score by Visual Analog Scale
• Symptom Assessment in Dry Eye (SAnDE) Score Assessment
• Conjunctival Lissamine Green Staining
• Conjunctival Hyperemia Grading
• Tear Film Break-up Time (TBUT)
• Schirmer's Test

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a binary participant-level measure: each participant either was counted as having reported any treatment-emergent adverse event during 8 weeks or was not. The arm summaries therefore use counts of affected participants and the number at risk. General explanation: a risk difference expresses the difference between the event proportions in two groups. A value of zero corresponds to equal observed proportions; positive and negative values indicate opposite directions under the comparison's stated ordering.

How should the risk differences be read?

For ALY688 Ophthalmic Solution 0.1% compared with vehicle, the posted risk difference is 0.043. Its confidence interval runs from -0.144 to 0.231. For ALY688 Ophthalmic Solution 0.4% compared with vehicle, the estimate is -0.065 and the interval runs from -0.242 to 0.111. These are absolute differences in the event proportion, not relative risks. The intervals include zero, meaning the posted summary data do not pin down the direction of the difference.

The registry also posts relative risk and odds ratio summaries for the primary comparisons. A relative risk compares the event proportions as a ratio, while an odds ratio compares event odds. These measures use different scales and interpretations from the risk difference. They do not remove uncertainty in the underlying data. As with the risk differences, their confidence intervals are broad. The estimates are unadjusted re-calculations from posted summary statistics, and the registry record does not provide sponsor-reported analyses.

What does a confidence interval convey?

General explanation: a confidence interval describes the range of estimates reasonably compatible with the data under the statistical method used. It communicates precision as well as direction. A narrow interval indicates more precision than a wide interval, while an interval spanning the null value for a difference does not rule out either direction. A confidence interval is not a guarantee that the true value lies in the interval, and it is not a probability statement about a particular treatment effect.

The posted p-values for the primary comparisons are unadjusted: 0.65 for the 0.1% comparison and 0.47 for the 0.4% comparison. General explanation: a p-value describes how unusual data at least as inconsistent with a null hypothesis would be under that hypothesis and the assumptions of the test. It does not measure the probability that the null hypothesis is true, the size of an effect, or the probability that a result will reproduce. The registry record does not report a prespecified analysis plan or say how these p-values relate to a planned confirmatory test.

How should the continuous outcomes be understood?

Ocular Discomfort Score and SAnDE are reported as mean changes with standard deviations. The reported comparison is a mean difference between an active arm and vehicle. General explanation: the mean describes the group average, and the standard deviation describes variability among participant-level values. A mean difference summarizes the contrast in averages, while its confidence interval conveys uncertainty around that contrast.

TBUT is reported as a least-squares mean with a standard error. A standard error describes uncertainty in an estimated mean, rather than variability among individual participants in the same way as a standard deviation. The registry record does not provide further details about the model used to obtain these least-squares means. The comparison statistics and planning illustrations for TBUT are based on approximate standard deviations derived from the posted standard errors; this limits how literally those planning illustrations should be interpreted.

All posted secondary comparisons are unadjusted. General explanation: when several outcomes or comparisons are examined, the chance of finding an apparently notable result by chance can increase. Adjusting for multiplicity or applying a prespecified hierarchy can address this issue, but the registry record does not report such a procedure. The listed secondary outcomes are described as exploratory in the official title, which is a reason to treat them as hypothesis-generating rather than as independent confirmation.

The record identifies the primary analysis population as the Safety Population, but does not report details of its definition, participant exclusions, missing-data handling, or analysis methods. Consequently, the posted summaries can be described, but the registry record does not support a full reconstruction of the original statistical analysis.

11. Confidence Intervals and Precision

Precision is limited by the size of the reported arms and by the width of the confidence intervals. Each arm has 46 participants. For the primary outcome, the risk-difference interval for ALY688 Ophthalmic Solution 0.1% versus vehicle ranges from -0.144 to 0.231; for the 0.4% comparison, it ranges from -0.242 to 0.111. Both intervals include zero and allow for differences in either direction. The point estimates alone therefore give an incomplete account of the uncertainty.

General explanation: a confidence interval presents a range of values compatible with the observed data under a specified method. Greater precision generally corresponds to a narrower interval. Here, the intervals are wide enough that the posted estimates do not sharply distinguish among a range of possible differences. They should not be interpreted as evidence that the groups are equivalent.

The continuous secondary comparisons are also imprecise. Their reported confidence intervals include zero, and several span values on both sides of the estimated mean difference. For TBUT, the posted comparisons use estimates based on approximate standard deviations, as indicated in the registry-derived statistics. That approximation adds another reason to interpret those planning and comparison summaries cautiously.

The unadjusted p-values are not substitutes for the intervals: the intervals show a range and direction of plausible contrasts, while p-values address compatibility with a null hypothesis under test assumptions. No sponsor-reported analyses are listed, and the registry record does not describe the original analysis plan. The results should therefore be read as estimates with substantial uncertainty, not as precise evidence of a particular effect size.

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 planning illustrations report participants per arm for 80% power and participants per arm for 90% power. They are based on the observed effect in each posted comparison and show how the illustrative sample size changes when the planning effect is set to 100%, 75%, or 50% of that observed effect. For these non-time-to-event outcomes, the values are participants per arm, not a total across arms or a count of events.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For example, the 75% row asks what per-arm sample size would be needed to detect an effect set to 75% of the observed estimate under those assumptions. The original trial's design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes an assumed probability of detecting the specified effect under the planning model if that effect were present; the 90% column uses a higher target probability under the same type of assumptions. They are planning targets, not descriptions of the probability that the completed study found a true effect. Smaller effects require more participants to detect with the same power target, which is why the entries increase as the planning fraction decreases.

These figures are illustrative planning calculations based on the observed effects, not observed power. Because observed effects from small arms can be unstable, they should not be treated as reliable forecasts of the size or design of a future trial.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.283; treatment proportion p₁ = 0.326; average p̄ = 0.304.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6507 = 1.2754.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6500 = 0.5471.
4. n = (1.2754 + 0.5471)² / (0.0435)² = 1,757.0, rounded up to 1,757 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
p0 <- 0.282608695652174                          # control proportion
p1 <- 0.326086956521739                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4201574)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 1,757 (80% power), 2,352 (90% power)
 75% of observed effect: n per arm = 3,093 (80% power), 4,140 (90% power)
 50% of observed effect: n per arm = 6,887 (80% power), 9,219 (90% power)
power.prop.test: 1757 
Simulated power at n = 1,757 per arm: 0.801 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 multiple secondary outcomes and two active-versus-vehicle comparisons for each outcome with posted quantitative results. The primary endpoint also has two active-versus-vehicle comparisons. The posted p-values are unadjusted. A multiplicity adjustment, testing hierarchy, or other prespecified strategy for interpreting the collection of comparisons is not reported in the registry record.

General explanation: examining multiple outcomes or contrasts can increase the chance that at least one result appears notable by chance. A prespecified strategy can distinguish primary confirmatory questions from exploratory comparisons and can control how evidence is assessed across tests. Without the strategy, individual unadjusted p-values should not be treated as if they were the only test conducted. This concern is especially relevant to secondary outcomes described as exploratory.

The registry reports no sponsor-reported analyses for the posted outcomes. It does not report whether there were interim analyses, how missing observations were handled, whether imputation was used, or whether sensitivity analyses were performed. Those details are not reported in the registry record and should not be inferred from the posted summaries.

The primary outcome is identified as belonging to the Safety Population, but the registry does not define that population in detail or explain how participants entered or were excluded from it. The arm summaries show 46 participants in each group. Whether all randomized participants contributed data to every secondary measure, and how missing measurements affected those summaries, is not reported in the registry record. These omissions limit assessment of potential bias from missingness or analysis-population choices.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: vascular pseudoaneurysm (2.2%).

The registry's serious adverse event summary reports 0 affected participants among 46 at risk in the vehicle arm, 1 among 46 in the ALY688 0.1% arm, and 0 among 46 in the ALY688 0.4% arm. The record lists vascular pseudoaneurysm at 2.2% among the top serious terms. Deaths are reported as 0 in each arm.

The separate summary of other adverse events reports 9 affected participants in the vehicle arm, 6 in the 0.1% arm, and 6 in the 0.4% arm, with 46 at risk in each arm. These figures should be read as reported categories and not added to the primary endpoint counts: the registry does not explain the relationship between the category definitions and the treatment-emergent adverse-event endpoint.

These are descriptive counts from a study with 46 participants per arm and an 8-week primary outcome timeframe. They do not establish comparative safety beyond this study, and the registry record does not provide further details on event severity, relatedness, timing, or adjudication.

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

The registry record documents a completed randomized study of two ALY688 concentrations and vehicle in participants with dry eye disease. For the primary safety endpoint, the observed counts were 13 participants with an adverse event in the vehicle arm, 15 in the 0.1% arm, and 10 in the 0.4% arm. The unadjusted comparisons have confidence intervals that include zero and are broad. The posted data therefore leave substantial uncertainty about the direction and size of differences in this outcome.

The record also contains exploratory symptom and tear-film summaries. Their estimates are mixed in direction, and the reported confidence intervals for the comparisons include zero. The registry record does not report quantitative results for all of the secondary outcome types it lists. The available secondary summaries do not provide a clear, uniform pattern across measures.

These findings do not establish that ALY688 improves dry-eye symptoms, that it does not improve symptoms, or that either concentration is equivalent to vehicle. They also do not establish an overall safety profile beyond the participants, outcome definitions, and 8-week timeframe represented in the record. A lack of a narrowly estimated difference is not the same as evidence of equivalence or absence of an effect.

General explanation: early-phase studies commonly include safety assessment and exploratory measures, but conclusions depend on the planned design, analysis, and data quality. In this case, the registry does not report the original sample-size justification, full statistical analysis plan, missing-data methods, or multiplicity procedure. Those omissions mean the posted results can be described with their uncertainty, but should not be stretched into broader claims about clinical benefit or risk.

17. Why This Trial Matters Statistically

This trial is statistically informative because it reports both participant-level safety counts and exploratory measures of symptoms and tear-film function in a randomized vehicle-controlled design. The three arms each include 46 participants, allowing direct descriptive comparisons while also making the limits of precision visible in the confidence intervals.

The primary outcome illustrates why an estimate should be read together with its uncertainty. The observed counts differ across arms, but the risk-difference intervals span values on either side of zero. The posted comparisons therefore leave room for several interpretations and do not sharply resolve the contrast between either concentration and vehicle. Reporting the interval makes that limitation clearer than relying on counts or p-values alone.

The record also shows why exploratory outcomes require care. Several different symptoms and clinical measures are listed, but numerical results are not available for every listed measure, the comparisons are unadjusted, and no multiplicity plan is reported. An apparent pattern across a subset of measures is not by itself confirmation, particularly when the estimates are uncertain.

Finally, the planning illustrations demonstrate the dependence of sample-size requirements on the effect chosen for detection. They are based on the observed estimates and stated planning assumptions, not on the trial's original design rationale. Read as illustrations rather than forecasts, they help distinguish the study's observed evidence from questions that a future, prospectively planned study might address.

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.

The registry record leaves important details of the study conduct and analysis unspecified. The original sample-size justification and design assumptions are not reported. The statistical analysis plan, outcome-specific analysis methods, handling of missing data, and any interim analyses are also not reported in the registry record. These gaps limit assessment of whether the posted comparisons correspond to prespecified analyses.

The primary endpoint is reported for the Safety Population, but that population is not defined in detail. The registry does not explain participant exclusions or whether the analysis population differed from the randomized population. It also does not describe how adverse events were collected, classified, judged for relatedness, or assessed for severity. The separate serious and other adverse-event summaries are not reconciled with the primary treatment-emergent adverse-event counts.

The reported arms each contain 46 participants, and the comparison intervals are wide. The findings are consequently imprecise for both the primary outcome and the posted exploratory comparisons. The registry lists six secondary outcome types, but quantitative results are not reported for all of them. The available comparisons are unadjusted, and a strategy for multiplicity is not reported.

TBUT comparisons rely on approximate standard deviations derived from posted standard errors for the planning calculations. The registry record does not provide enough detail to reconstruct the underlying model or assess assumptions for the least-squares means. Finally, the 8-week primary timeframe does not describe outcomes beyond that observation period. These are limitations of interpretation based on the registry record, not claims about information that may exist elsewhere.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Phase 1/2a Safety and Efficacy of ALY688 Ophthalmic Solution in Subjects With Dry Eye Disease — NCT04201574.
• Registry record last updated 2023-06-22; status last verified 2023-05.
• Results first posted 2023-06-22.
• 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

NCT04201574 is a completed randomized, double-masked, vehicle-controlled Phase 1/2a study of ALY688 ophthalmic solution in dry eye disease. Enrollment was 138, with 46 participants in each of the vehicle, ALY688 0.1%, and ALY688 0.4% arms in the posted primary outcome. The primary endpoint counted participants reporting treatment-emergent adverse events over 8 weeks.

The observed primary counts were 13, 15, and 10, respectively. Unadjusted risk-difference estimates have confidence intervals that include zero and are broad. Exploratory results are posted for ocular discomfort, SAnDE, and TBUT; numerical results for other listed secondary outcomes are not reported in the registry record. The original statistical plan, missing-data methods, and multiplicity strategy are not reported.