Efficacy and Safety Assessment of T4090 Ophthalmic Solution Versus Rhopressa® Ophthalmic Solution in Patients With Open-angle Glaucoma or Ocular Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Assessment of T4090 Ophthalmic Solution Versus Rhopressa® Ophthalmic Solution in Patients With Open-angle Glaucoma or Ocular Hypertension (NCT06394973), a randomized phase 2 study. The primary outcome is Mean Diurnal IOP.

2. Clinical Question

3. Trial Design

This completed Phase 2 study was a randomized, single-masked, parallel-group trial sponsored by Laboratoires Thea. Its stated purpose was to compare the ocular hypotensive efficacy and safety of T4090 at 0.2% and 0.3% with Rhopressa® ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. The registry record lists an enrollment of 161. It records a start date of 2024-08-05 and a primary completion date of 2024-11-21.

The three listed treatment groups were T4090 0.2%, T4090 0.3%, and Rhopressa®. For the primary endpoint summaries, the reported group sizes were 45.0, 42.0, and 47.0, respectively. These analysis counts should be read as the counts attached to the posted endpoint summaries, not as a replacement for the registry enrollment figure. The registry record does not explain the relationship between enrollment and the endpoint analysis counts.

Random allocation and a parallel-group structure support comparisons between assigned treatment groups, while single masking can reduce some forms of bias. However, the record does not say who was masked, how allocation was generated or concealed, or what procedures were used to maintain masking. Detailed treatment schedules and the duration of treatment are not reported in the registry record beyond the Week 7 primary endpoint assessment.

The registry record identifies one outcome measure, Mean Diurnal IOP, and two sponsor-reported analyses. It does not report secondary outcome measures. The primary outcome is a continuous measure summarized with a mean and standard deviation. The endpoint is change from baseline at Week 7 in the study eye, while the sponsor analyses are labeled as comparisons of final values using mixed models. These are related but not interchangeable descriptions of an analysis.

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: Primary estimand - Full Set Analysis

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.

6. Primary Endpoint

The registry lists the primary outcome as Mean Diurnal IOP, measured over The primary efficacy endpoint is the change from baseline (D1) at Week 7 in the mean diurnal IOP in the study eye..

The primary endpoint is change from baseline at Week 7 in mean diurnal intraocular pressure in the study eye. Intraocular pressure, or IOP, was measured with a calibrated Goldmann applanation tonometer by the investigator at 8:00 AM, 10:00 AM, and 4:00 PM. The mean of those three daily measurements defines the mean diurnal value. The reported endpoint is therefore a mean of repeated measurements within a day, evaluated as change from the baseline assessment designated D1.

Using a daily mean can represent pressure across several specified times rather than relying on a single reading. This is useful because the question concerns a measure that can vary over the course of the day. A change-from-baseline endpoint expresses the Week 7 value relative to each participant’s starting value; a negative change indicates a lower value than baseline. The posted group means are negative, and the group standard deviations describe the spread of individual changes around each group mean.

The endpoint is clinically relevant to the trial’s stated aim of comparing ocular hypotensive efficacy, but it does not by itself describe every aspect of efficacy or safety. The registry record specifies the study eye and the Full Set Analysis as the primary estimand population. It does not further define how the study eye was selected or provide the detailed estimand strategy for events such as treatment discontinuation or missing Week 7 measurements.

7. Results Posted in the Registry

• T4090 0.3%: mean -4.73 versus -5.07 on control; difference 0.34 (95% CI -0.86 to 1.54), standardized effect d = 0.12; z-test p = 0.578.
• Rhopressa®: mean -4.60 versus -5.07 on control; difference 0.47 (95% CI -0.72 to 1.66), standardized effect d = 0.16; z-test p = 0.438.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: each participant has a numerical change in mean diurnal IOP, measured in mmHg. For continuous outcomes, a group mean describes the average observed value, while a standard deviation describes variation among the observations around that mean. The posted values are group means and standard deviations for change from baseline, with separate group sizes. These summaries allow an unadjusted comparison of group averages, but they do not preserve participant-level information or adjust for other variables.

What does a mean difference represent?

A mean difference is one group’s average minus the comparator group’s average, using a stated ordering. The recalculated comparisons use T4090 0.2% as the reference: the reported estimate for T4090 0.3% is 0.34 mmHg, and the estimate for Rhopressa® is 0.47 mmHg. Because the outcome is change from baseline, the sign must be read alongside the group means. The T4090 0.2% mean is more negative than either comparator mean, so the positive contrasts indicate less-negative average changes in those comparator groups. A difference is an estimate, not a guarantee that the underlying population difference has the same value.

Why does the standard deviation matter?

The standard deviation describes spread in the endpoint among participants. It is not the same as the standard error, which describes the uncertainty in an estimated mean. In general, the precision of a group mean depends both on the variability of observations and on the amount of information contributing to the estimate. Comparisons use uncertainty from both groups. The posted recalculations use the observed group standard deviations rather than an approximate substitute.

In general, over-dispersion occurs when observed variability is greater than a statistical model expects. Ignoring it can make standard errors too small and confidence intervals too narrow. Here, the outcome is summarized as a continuous measure with standard deviations, and over-dispersion is not identified as a reported feature of the analysis. No claim about a special over-dispersion adjustment can be made from the registry record.

What does a confidence interval add?

A confidence interval presents a range of values compatible with the estimate under the calculation’s assumptions. It conveys precision as well as direction: a narrow interval indicates greater precision, while a wide interval leaves more plausible values unresolved. For the recalculated comparisons, both intervals include zero, so the summaries do not rule out no mean difference. Their breadth also leaves room for differences in either direction. These are unadjusted recalculated intervals, not intervals reported for the sponsor’s mixed models analyses.

How should the p-values be read?

The recalculated p-values are unadjusted. In general, a p-value measures compatibility between the observed data and a specified null model; it is not the probability that the null hypothesis is true, and it does not measure clinical importance. A larger p-value does not prove equivalence or show that any difference is absent. Equivalence or non-inferiority requires a prespecified margin and an appropriate analysis, neither of which is reported in the registry record.

The sponsor-reported p-values come from mixed models analyses of final values. Mixed models are a general class of methods for modeling outcomes while accounting for specified structure in data, such as repeated observations or grouping. The registry record does not give enough detail about the model specification, covariance structure, adjustment variables, or handling of missing measurements to evaluate those choices. The sponsor’s final-value analyses should therefore be read as reported results, without assuming unreported model details.

What can planning calculations show?

Planning calculations relate a target effect, outcome variability, significance level, allocation, and desired power to a sample-size estimate. The posted illustrations use the observed effect and show alternative assumptions in which the effect to detect is a stated fraction of that effect. They are hypothetical planning estimates, not a reconstruction of the trial’s original design. The original sample-size assumptions and justification are not reported in the registry record.

In general, a smaller target effect is harder to distinguish from random variation and therefore calls for more participants under otherwise similar assumptions. Power is the probability, under a specified assumed effect and model, of detecting that effect using the planned test. The 80% and 90% columns correspond to different desired chances of detecting the target effect. They do not describe the probability that the trial’s conclusion is correct. Details of the statistical plan, including whether any interim analyses or multiplicity adjustments were planned, are not reported in the registry record.

10. Confidence Intervals and Precision

The unadjusted recalculated mean difference comparing T4090 0.3% with T4090 0.2% is 0.34 mmHg, with a 95% interval from -0.858 to 1.538. The recalculated Rhopressa® versus T4090 0.2% difference is 0.47 mmHg, with a 95% interval from -0.718 to 1.658. Each interval includes zero. Under the calculation assumptions, the summaries therefore do not exclude no difference between the compared group means.

The intervals also extend to values on either side of zero, so they leave uncertainty about both direction and size. Their interpretation is about the precision of the unadjusted estimates, not about the probability that a particular value is true. The interval limits should be considered along with the point estimates and the group means; a point estimate alone can give an incomplete impression of what the data allow.

These confidence intervals are recalculated from posted summary statistics, not sponsor-reported intervals. The registry record does not report confidence intervals for the mixed models estimates of final values. Accordingly, the precision of those sponsor analyses cannot be assessed from the posted estimates and p-values alone. The recalculated intervals also do not account for any adjustments or model features that may have been used in the sponsor analysis but are not documented in the registry record.

Precision is not the same as clinical importance. The registry record does not state a threshold for a meaningful IOP difference, so the intervals cannot be classified against such a threshold. The results support an uncertainty-focused reading: the observed contrasts are small relative to the range of values still compatible with the recalculated summaries, and neither comparison establishes equivalence.

11. 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 estimates are participants per arm, not total events. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They use the observed effect as a starting point, with alternative targets corresponding to 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column indicates the number of participants per arm estimated to give an 80% chance of detecting the target effect under those planning assumptions. The 90% power column gives the corresponding estimate for a 90% chance. For example, the comparison of T4090 0.3% with T4090 0.2% gives estimates of 1,098 participants per arm for 80% power and 1,470 participants per arm for 90% power when planning for 100% of the observed effect. For Rhopressa® versus T4090 0.2%, the corresponding estimates are 603 and 808 participants per arm.

The alternative rows illustrate how sensitive planning is to the assumed effect: when planning for 75% or 50% of the observed effect, the estimates are larger. Smaller effects require more participants to distinguish them from random variation when other assumptions remain the same. The accompanying curve represents the same general relationship between the target effect and planning requirements; it is not a separate trial result. These figures are planning illustrations based on the observed effects, not observed power for the completed trial.

12. 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 = 0.340; pooled standard deviation σ = 2.843.
2. n = 2 × (1.96 + 0.842)² × 2.843² / 0.340² = 1,097.8, rounded up to 1,098 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 <- 0.34                      # observed difference in means
sigma <- 2.84323262585141                     # 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(6394973)
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 = 1,098 (80% power), 1,470 (90% power)
 75% of observed effect: n per arm = 1,952 (80% power), 2,613 (90% power)
 50% of observed effect: n per arm = 4,392 (80% power), 5,879 (90% power)
power.t.test: 1098.7 
Simulated power at n = 1,098 per arm: 0.799 (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.

13. Analyses Reported by the Sponsor

The registry reports two sponsor analyses using mixed models and labeling the parameter as mean difference in final values. For T4090 0.2% versus Rhopressa®, the reported estimate is -0.49 with p = 0.376. For T4090 0.3% versus Rhopressa®, the reported estimate is -0.36 with p = 0.518. Confidence intervals for these estimates are not reported in the registry record.

The recalculations use the posted group means and standard deviations for change from baseline. They are unadjusted comparisons, rather than reproductions of the sponsor’s mixed models. A final-value contrast and a change-from-baseline contrast can differ because they are different outcome summaries, and the sponsor’s model may also use information or adjustments not documented in the registry record. Therefore, the reported values should be presented in their own terms and should not be combined with the recalculated estimates as though they were the same analysis.

The registry record does not flag a discrepancy. The sponsor-reported analyses remain the record’s own analyses, while the recalculations help describe the posted summary statistics and their approximate uncertainty. Without further model details or sponsor confidence intervals, the precision and exact analytic choices behind the mixed models results cannot be independently evaluated from the record.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no secondary outcomes posted. It reports two sponsor analyses, each comparing one T4090 concentration with Rhopressa®. The record does not report whether the statistical plan treated these comparisons as a family, whether an adjustment for multiple comparisons was planned, or how the primary endpoint and comparisons were prioritized. The recalculated p-values are unadjusted, so they should not be interpreted as multiplicity-controlled evidence.

Multiplicity arises when several hypotheses are tested: the chance of at least one apparently notable result can increase as more tests are considered. In general, analysis plans can address this through prespecified testing sequences or adjustment methods. No such plan is reported in the registry record, so it is not possible to determine whether the sponsor analyses used any procedure of this kind. The results are best read as the posted comparisons rather than as a fully documented testing strategy.

The registry identifies the primary estimand population as the Full Set Analysis, but it does not provide a detailed definition of that population or the rules governing inclusion in the endpoint analysis. It also does not report how missing Week 7 values were handled, whether participants who discontinued treatment remained in the analysis, or what assumptions were used for missing data. These details matter because missing measurements can affect both the composition of the analysis population and the estimated treatment contrast.

Randomization, masking, and the parallel-group design are reported, but the record does not provide the allocation method, masking procedures, or statistical analysis plan. Interim analyses are not reported in the registry record. These omissions do not establish that a procedure was or was not used; they limit what can be assessed from the posted information. In particular, the impact of missing data, multiplicity, or any interim decision process cannot be evaluated without further documentation.

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: lung adenocarcinoma (1.9%).

The registry reports serious adverse events among participants at risk in each group. There were 0 serious adverse events among 53 participants at risk in the T4090 0.2% group, 0 among 53 in the T4090 0.3% group, and 1 among 53 in the Rhopressa® group. The listed serious event term is Lung Adenocarcinoma, reported as 1.9%. Deaths were reported as 0 in each group.

These are descriptive counts. A zero count means that no event was reported in that group during the registry’s stated safety reporting, not that the possibility of such an event is ruled out. A single event in a group is also too limited, by itself, to establish a treatment-related difference. The registry record does not provide enough detail to assess event timing, relatedness, severity criteria, or follow-up completeness.

The record separately reports other adverse events affecting 46 participants in each T4090 group and 36 in the Rhopressa® group, with 53 at risk in each group. Those figures are not serious adverse event counts and should not be conflated with the serious-event summary. Safety counts do not establish causality or provide a precise comparative risk estimate. They should be read alongside the trial’s limited size and the registry’s available reporting detail, rather than as definitive evidence for or against a safety difference.

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

The posted efficacy summaries show decreases in mean diurnal IOP from baseline in all three groups. The mean changes were -5.07 mmHg with T4090 0.2%, -4.73 mmHg with T4090 0.3%, and -4.6 mmHg with Rhopressa®. These are observed group averages at the Week 7 endpoint, not guarantees about an individual participant’s response. The standard deviations indicate variability around those averages.

The unadjusted recalculated contrasts have confidence intervals that include zero, and the sponsor-reported mixed models analyses have p-values of 0.376 and 0.518. Taken together, the posted results do not establish a clear difference between the compared groups. They also do not establish equivalence, non-inferiority, or that treatments have identical effects. Such conclusions require a defined margin and an analysis designed to assess that question, neither of which is reported in the registry record.

The estimates are not a complete account of the study. The sponsor analyses use final values, while the recalculations compare change-from-baseline summaries. Sponsor confidence intervals and detailed model specifications are not reported, so the precision and assumptions of those analyses cannot be fully assessed. The registry also does not report secondary outcomes, the handling of missing data, or a multiplicity plan.

Safety information is likewise limited to registry counts. The serious adverse event listing includes one event in the Rhopressa® group and none in the T4090 groups, with no deaths reported. These descriptive findings do not establish that a treatment caused or prevented an event, and they do not provide a precise comparison of safety.

Overall, the record describes a randomized Phase 2 comparison and posts efficacy and safety summaries, but it leaves important questions about analysis details and precision unresolved. The results should be understood as estimates from this study, not as a definitive answer about comparative clinical effects or safety.

17. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates how a randomized comparison can produce visible differences in group averages while leaving substantial uncertainty about the underlying contrasts. The three posted mean changes are all negative, and the recalculated comparisons are modest relative to their confidence interval widths. Reading the estimates together with uncertainty avoids treating the largest or smallest mean as a conclusive ranking.

It also demonstrates why the analysis definition matters. The primary endpoint is a change from baseline, whereas the sponsor’s mixed models results are labeled as final-value comparisons. Both can be relevant, but they answer questions through different summaries and methods. Without the sponsor model details and confidence intervals, a reader cannot assume the two sets of results should match numerically or carry the same precision.

The planning illustrations show the relationship between a target effect and the amount of information required to detect it under stated assumptions. The required sample size rises as the assumed effect becomes smaller. That is a general design principle, not evidence that the completed study was underpowered or that its original design was inappropriate; its original sample-size rationale is not reported in the registry record.

Finally, the safety results demonstrate the limits of interpreting sparse event counts. A zero count is not proof of absence of risk, and one event does not establish a treatment-related excess. Statistical reading therefore requires attention to the outcome definition, analysis population, uncertainty, and completeness of reporting—not just the direction of an estimate or whether a p-value crosses a threshold.

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 contains limited information about trial conduct and analysis. It identifies the study as randomized and single-masked but does not explain sequence generation, allocation concealment, who was masked, or how masking was maintained. Detailed arm descriptions and administration schedules are not reported. As a result, important aspects of risk of bias and treatment implementation cannot be assessed from this record.

The primary endpoint is defined as change from baseline at Week 7, but the record does not fully explain study-eye selection, analysis-population inclusion rules, missing-measurement handling, or the statistical estimand strategy. The sponsor’s mixed models analyses are reported without confidence intervals or details such as model specification and covariate adjustment. The recalculated comparisons are unadjusted and based on group summary statistics, so they cannot reproduce a participant-level model.

The registry reports no secondary outcome measures and does not describe a multiplicity strategy, interim analyses, or the original sample-size justification. Consequently, the intended hierarchy of analyses and the relationship between the trial’s design assumptions and the posted results are not assessable. The sample-size illustrations are based on observed effects and stated planning assumptions rather than the study’s original design.

Safety reporting is also limited. The serious adverse event counts and named term are available, but the record does not provide event-level detail on timing, relatedness, or follow-up. The treatment groups’ safety counts should therefore be interpreted descriptively. These limitations concern the information available in the registry record; they do not establish that unreported procedures or analyses were absent.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy and Safety Assessment of T4090 Ophthalmic Solution Versus Rhopressa® Ophthalmic Solution in Patients With Open-angle Glaucoma or Ocular Hypertension — NCT06394973.
• Registry record last updated 2026-01-02; status last verified 2025-12.
• Results first posted 2026-01-02.
• 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

NCT06394973 is a completed Phase 2 randomized, single-masked, parallel-group study sponsored by Laboratoires Thea. It enrolled patients with open-angle glaucoma or ocular hypertension and compared T4090 ophthalmic solution at 0.2% and 0.3% with Rhopressa® ophthalmic solution. The registry lists enrollment of 161 and records the study start as 2024-08-05 and primary completion as 2024-11-21.

The primary outcome was change from baseline at Week 7 in mean diurnal IOP in the study eye, based on measurements at 8:00 AM, 10:00 AM, and 4:00 PM. Posted group means show negative changes in all groups. Unadjusted recalculated comparisons have confidence intervals that include zero, while the sponsor-reported mixed models analyses of final values report p-values of 0.376 and 0.518. The registry record does not report sponsor confidence intervals, detailed model specifications, a multiplicity plan, or missing-data methods. Serious adverse event counts were 0, 0, and 1 across the listed groups, with no deaths reported.