Pharmacodynamics of a Fixed Dose Combination of 0.34% Tropicamide and 2.5% Phenylephrine Hydrochloride, Eye Drop, Solution: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacodynamics of a Fixed Dose Combination of 0.34% Tropicamide and 2.5% Phenylephrine Hydrochloride, Eye Drop, Solution (NCT07075224), a randomized phase 1, phase 2 study. The primary outcome is Change in Pupil Diameter at 60 Minutes From the Time of First Dose Versus Baseline, as Measured With Photo (Central Reading).

2. Clinical Question

The endpoint is pharmacodynamic: it concerns the change in pupil size following treatment, rather than a patient-centered clinical outcome. The study also lists secondary questions about the time to sufficient mydriasis, reaching specified pupil diameters, time to maximal dilation, pupil size at other timepoints, and ocular discomfort. The record describes the objective as exploring pharmacodynamic effects and safety in healthy volunteers. It does not establish what the observed pupil-diameter difference would mean for people with an eye condition or for clinical care.

3. Trial Design

The registry describes a randomized, single-masked crossover study, listed as Phase 1 and Phase 2. Participants received both IMP 08P2002F0 and Mydriasert® insert in different sequences. The record lists one sequence beginning with IMP 08P2002F0 and another beginning with Mydriasert® insert. In each intervention period, the insert was kept on the eye for one hour, retrieved, and followed by rinsing with NaCl. The record describes a washout of 2-7 days between intervention periods and 6 hours of follow-up for each intervention.

A crossover design means that treatment comparisons involve measurements from treatment periods within the study, rather than assigning each participant to just one treatment throughout. That structure can make within-participant comparisons informative, but interpretation depends on how the analysis accounts for the repeated measurements and the sequence and period structure. Those analysis details are not reported in the registry record.

The listed enrollment is 20, and each treatment arm reports 20 observations for the primary endpoint. Because this is a crossover study, the treatment-arm entries should not be read as two separate parallel groups of participants. The primary endpoint population is specified as one randomized eye per participant. The study status is completed. The listed start date is 2025-11-01 and the primary completion date is 2025-11-09. Unither Pharmaceuticals, France, is listed as sponsor. The registry record does not identify who was masked, explain the allocation procedure, or give the original sample-size justification.

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.

Period 1

Period 2

Analysis population for the primary outcome, as defined in the registry: Only 1 eye (the randomized eye) is measured per participant.

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 Change in Pupil Diameter at 60 Minutes From the Time of First Dose Versus Baseline, as Measured With Photo (Central Reading), measured over 60 minutes.

The primary endpoint is the mean change in pupil diameter, measured in millimeters, at 60 minutes from the time of first dose versus baseline. Pupil diameter was measured with photo and central reading; only the randomized eye was measured per participant. The posted treatment means are changes from baseline, so a positive mean indicates an increase in diameter relative to baseline on average.

Pupil diameter is a direct pharmacodynamic measure for a study whose stated purpose is to explore pupil dilation. Measuring change from baseline places the post-dose measurement in the context of each participant’s starting pupil size, while the 60-minute timepoint provides a defined point for comparing the treatments. Central reading is the stated measurement approach; the registry record does not describe the reading procedure or how measurement variability was assessed.

The primary measure is continuous, and the record reports a mean and standard deviation for each treatment. A mean describes the average change, while the standard deviation describes variation in individual measurements around that mean. The endpoint does not by itself summarize duration of dilation, comfort, safety, or whether a particular pupil diameter is clinically sufficient. Those topics appear among the listed secondary outcomes, but their results and analysis details are not included in the primary comparison.

7. Results Posted in the Registry

• IMP 08P2002F0: mean 3.29 versus 3.28 on control; difference 0.01 (95% CI -0.54 to 0.56), standardized effect d = 0.01; z-test p = 0.971.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: pupil diameter change is measured in millimeters, and the registry describes the reported treatment values as means with standard deviations. The comparison is a mean difference, with IMP 08P2002F0 compared against Mydriasert® insert. The posted means are 3.29 mm for IMP 08P2002F0 and 3.28 mm for Mydriasert® insert; the posted mean difference is 0.01 mm.

What does a mean describe?

A mean is the arithmetic average of the measurements in a treatment group or period. It gives a concise description of the central value, but it does not show the full distribution. Two treatments can have similar means while individual measurements vary substantially. For that reason, the mean is read alongside a measure of spread and an uncertainty interval for the treatment comparison.

The standard deviations are 0.81 mm with IMP 08P2002F0 and 0.95 mm with Mydriasert® insert. Standard deviation describes variability among measurements around the mean; it is not the uncertainty in the mean difference. The registry record does not provide a distribution plot or participant-level measurements for this endpoint. The standard deviations therefore give some information about spread but cannot show whether the distributions are skewed, contain outliers, or differ in other ways.

Why does the crossover design matter?

In a crossover study, participants receive treatments in separate periods. Measurements from the same participant can be related, so a suitable treatment comparison may use the within-participant relationship. That relationship can affect the uncertainty of the difference. The registry record identifies the study as randomized and crossover and lists the two treatment sequences, but it does not report whether the comparison was based on paired observations or specify a statistical model. It also does not report how sequence, period, or carryover effects were handled. The posted arm means and standard deviations alone do not reveal those choices.

The intervention descriptions state that there was 6 hours of follow-up for each intervention and a washout of 2-7 days between periods. These design details help explain the timing, but they do not establish that carryover was absent or that the washout was sufficient for every outcome. Evidence about those questions is not reported in the registry record.

How should the p-value be read?

The posted p-value is unadjusted and equals 0.971. A p-value describes how compatible the observed comparison is with a specified null model, conditional on the model and its assumptions. It is not the probability that the null hypothesis is true, and it is not the probability that the treatments are the same. A high p-value does not prove equivalence or demonstrate that an effect is absent. The registry record does not report the full test specification or whether the calculation accounts for the crossover structure.

Because the p-value is unadjusted, it should not be treated as a multiplicity-adjusted result across the primary and secondary outcomes. The record lists multiple outcome measures, but a testing hierarchy or adjustment procedure is not reported in the registry record. The presence of several outcomes makes that information relevant when interpreting isolated significance tests.

What does the confidence interval add?

A confidence interval gives a range of values compatible with the data and the statistical method used, under that method’s assumptions. The posted interval for the mean difference has a lower bound below zero and an upper bound above zero. Thus it includes no difference and values on either side. It conveys uncertainty that cannot be captured by the point estimate alone. Its interpretation depends on the analysis method, which is not described in detail in the registry record.

The calculated planning illustrations use the observed effect and assumptions stated with the planning material: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record. These illustrations are planning calculations, not a reconstruction of the trial’s design or analysis.

The registry record does not report the missing-data procedure, the analysis population beyond the primary endpoint statement about the randomized eye, or a protocol-defined approach to outliers. It also does not report whether there were interim analyses. These omissions limit the ability to reproduce or fully evaluate the statistical analysis from the registry entry alone.

10. Confidence Intervals and Precision

The point estimate for the mean difference is 0.01 mm, but a point estimate does not show how uncertain the comparison is. The posted confidence interval has a lower limit below zero and an upper limit above zero. Its span therefore includes the possibility of a small difference favoring either treatment, as well as no difference. The interval should be considered together with the p-value of 0.971 and the study’s crossover design.

A confidence interval is not a range containing a fixed proportion of individual participants’ measurements. It expresses uncertainty about the estimated treatment difference under the statistical method used. The standard deviations describe spread among the endpoint measurements; the confidence interval addresses precision of the comparison. These are distinct quantities and answer different questions.

The registry record does not report a clinically important difference threshold for pupil diameter. Without such a threshold, the interval cannot be classified as excluding clinically meaningful differences. It also does not report a prespecified equivalence or non-inferiority margin. The fact that the interval crosses zero is not proof that the treatments have identical effects, and the small point estimate alone does not show that the estimate is precise enough to rule out other differences.

Precision also depends on the analysis matching the crossover structure. The registry entry does not explain how repeated measurements, sequence, period, or potential carryover were handled. Consequently, the posted interval can be described as the registry’s reported uncertainty, but its construction cannot be fully assessed from the record.

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 sample-size figures are planning illustrations based on the observed effect, not a description of the enrollment needed for the original trial. The listed values are participants per arm, not total event counts. The assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column describes the planned number of participants per arm under those assumptions for an 80% chance of detecting the chosen effect if that effect is present and the assumptions hold. The 90% power column describes the corresponding planning target for a 90% chance. These are design calculations, not guarantees about what a future study will find. The figures are not observed power.

The rows express planning for the full observed effect, 75% of the observed effect, and 50% of the observed effect. A smaller target effect requires more participants to distinguish it from random variation with the same stated power and significance level. The curve is a visual way to read that relationship across effect sizes; it does not change the assumptions or turn the calculations into evidence about the trial’s actual power.

The observed mean difference is 0.01 mm, so these illustrations are anchored to a very small observed difference. They should be treated cautiously as planning examples, especially because the registry record does not report whether the original design used a different target effect, crossover-specific assumptions, or another method.

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 = 0.010; pooled standard deviation σ = 0.883.
2. n = 2 × (1.96 + 0.842)² × 0.883² / 0.010² = 122,332.6, rounded up to 122,333 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 <- 0.0100000000000002                      # observed difference in means
sigma <- 0.882779700718135                     # 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(7075224)
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 = 122,333 (80% power), 163,769 (90% power)
 75% of observed effect: n per arm = 217,481 (80% power), 291,145 (90% power)
 50% of observed effect: n per arm = 489,331 (80% power), 655,075 (90% power)
power.t.test: 122333.6 
Simulated power at n = 122,333 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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures and identifies a range of secondary questions, including time to sufficient mydriasis, pupil diameter thresholds, time to maximal dilation, pupil measurements at other timepoints, pupil-size distributions, and ocular discomfort. It also lists 10 secondary outcomes as posted. The primary comparison is accompanied by an unadjusted p-value.

When many outcomes or timepoints are examined, the chance of observing at least one apparently notable result can increase, even if there is no true effect for any outcome. Statistical approaches can address multiplicity by defining a hierarchy of tests, adjusting significance thresholds, or distinguishing primary confirmatory questions from exploratory questions. The registry record does not report a multiplicity strategy, a testing hierarchy, or adjusted results. The primary p-value should therefore be read as unadjusted, not as evidence that accounts for all outcome comparisons.

The registry record lists 0 analyses. It does not describe the analysis population for outcomes beyond the primary endpoint statement that only the randomized eye was measured per participant. Missing-data handling, imputation, exclusions, and rules for incomplete treatment periods are not reported in the registry record. The record also does not explain whether the crossover analysis included within-participant correlation, treatment sequence, period effects, or carryover.

These omissions matter because they affect what data contribute to each estimate and how uncertainty is calculated. In a crossover study, missing measurements in one period may affect the available paired comparison differently from missing measurements in both periods. Without the analysis plan and outcome-level results, the registry entry does not permit a complete assessment of how missing observations or the multiple listed outcomes influenced the findings.

14. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry lists serious adverse event counts by treatment group. For IMP 08P2002F0, 0 serious adverse events were recorded among 20 at risk; for Mydriasert® insert, 0 were recorded among 20 at risk. Deaths were 0 in each group. These are counts recorded in the registry, not estimates that establish the absence of risk.

The record separately lists other, non-serious adverse events: 0 affected for IMP 08P2002F0 and 1 affected for Mydriasert® insert. The specific event term is not reported in the registry record. Serious and other adverse events are separate categories and should not be combined when describing the results.

These counts are descriptive. With an enrollment of 20 and a short intervention and follow-up schedule, the record offers limited information about uncommon events or safety beyond the recorded observation period. It does not report detailed event narratives, severity for the non-serious event, relatedness assessments, or a comparative safety analysis. The figures should therefore be read as registry counts, not as proof that either treatment is free of adverse effects or as a basis for treatment decisions.

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

The posted primary result describes the average change in pupil diameter at 60 minutes in this study. The mean change was 3.29 mm with IMP 08P2002F0 and 3.28 mm with Mydriasert® insert, with a posted mean difference of 0.01 mm. The confidence interval extends to both sides of zero, and the unadjusted p-value is 0.971. Together, these statistics describe a close observed mean comparison with uncertainty that does not rule out differences in either direction.

The result does not establish that the treatments are equivalent. A conclusion of equivalence would require a prespecified margin and an analysis designed to test whether the uncertainty lies within that margin. Neither is reported in the registry record. Nor does a non-significant test demonstrate that there is no treatment effect. It means that the comparison, as reported, does not provide strong evidence against the null hypothesis under the test’s assumptions.

The endpoint is a pharmacodynamic measurement in healthy volunteers. It does not directly answer questions about clinical benefit, symptom relief, patient experience beyond the listed ocular-discomfort outcome, or outcomes in people with a particular eye condition. Results for the listed secondary outcomes are not described in the posted primary comparison.

The trial is a crossover, but the registry does not describe the analysis handling of within-participant measurements, sequence, period effects, or carryover. The precision of the comparison therefore cannot be fully judged from the registry record. The safety counts are similarly descriptive and do not establish comparative safety. The appropriate scope of interpretation is limited to the recorded endpoint, timepoint, study population, and reported analysis.

16. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should not be reduced to its point estimate or p-value. The observed mean difference is 0.01 mm, while the confidence interval extends across zero. The estimate is close to zero, but the interval and the missing clinically important difference threshold determine how much can be concluded about precision and practical relevance. A high p-value is not an equivalence result.

The crossover design is statistically important because the same participant can contribute measurements under both treatments. A paired analysis can use the relationship between those measurements, whereas treating them as independent would not reflect the design. The registry identifies the crossover structure but does not report the analysis method or how period and sequence features were handled. That gap limits independent evaluation of the comparison.

The study also emphasizes the distinction between a planning illustration and an original sample-size calculation. The listed illustrations use the observed effect and specified assumptions; they do not establish the trial’s original rationale and are not observed power. This distinction is especially relevant when the observed difference is small, because planning around a small target effect can imply very large participant requirements under the stated assumptions.

Finally, the record lists several secondary outcomes but does not describe multiplicity handling or provide the associated estimates in the primary comparison. Transparent reporting of analysis methods, missing-data handling, and outcome-specific uncertainty would help readers understand how the primary result fits within the broader study.

17. 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 gives a limited account of the analysis. It does not report the statistical model, whether the treatment comparison used paired data, how sequence and period effects were handled, or whether carryover was considered. Those details are particularly relevant to interpreting a crossover study and its confidence interval.

The record does not report a clinically important difference threshold, an equivalence or non-inferiority margin, or the original sample-size justification. The planning illustrations are based on the observed effect and stated assumptions, rather than documenting the trial’s own design calculations. The registry record also does not report interim analyses.

Although secondary outcomes are listed, the primary comparison does not give their estimates or uncertainty. A multiplicity strategy, missing-data rules, imputation method, and detailed analysis populations are not reported in the registry record. The record also does not provide participant-level data or a fuller description of measurement procedures, so the variability and robustness of the results cannot be independently explored from the registry entry.

The study concerns healthy volunteers and a 60-minute pupil-diameter endpoint. Its primary result does not by itself address other populations, longer-term effects, the secondary outcomes, or clinical outcomes. The safety information consists of event counts and does not include detailed event descriptions or a full comparative safety analysis. These limitations constrain interpretation to the specific measurements and registry information available.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Pharmacodynamics of a Fixed Dose Combination of 0.34% Tropicamide and 2.5% Phenylephrine Hydrochloride, Eye Drop, Solution — NCT07075224.
• Registry record last updated 2026-06-17; status last verified 2026-05.
• Results first posted 2026-06-17.
• 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.

21. Record Summary

The registry describes a completed randomized, single-masked crossover study, listed as Phase 1 and Phase 2, of IMP 08P2002F0 versus Mydriasert® insert in healthy volunteers. Enrollment is 20. The primary endpoint is mean change in pupil diameter at 60 minutes from first dose versus baseline, measured by photo with central reading in one randomized eye per participant.

The posted mean changes are 3.29 mm for IMP 08P2002F0 and 3.28 mm for Mydriasert® insert; the mean difference is 0.01 mm, with an unadjusted p-value of 0.971. The posted confidence interval spans values on both sides of zero. The registry lists no serious adverse events or deaths in either group. Key analysis details, including crossover modeling, multiplicity handling, and missing-data methods, are not reported in the registry record.