A Study of Safety and Efficacy of UNR844 Chloride (UNR844-Cl) Eye Drops in Subjects With Presbyopia.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Safety and Efficacy of UNR844 Chloride (UNR844-Cl) Eye Drops in Subjects With Presbyopia. (NCT03809611), a randomized phase 2 study. The primary outcome is Change in Binocular Distance-corrected Near Visual Acuity (DCNVA) From Baseline.

2. Clinical Question

3. Trial Design

The registry describes a Phase 2, randomized, placebo-controlled, double-masked, parallel-group study of topical UNR844-Cl in subjects with presbyopia. The official title describes the study as lasting 3 months. Participants were assigned to UNR844-Cl ophthalmic solution or placebo ophthalmic solution, with both regimens described as twice-daily dosing. The active solution concentration was 1.5%. The study was sponsored by Novartis Pharmaceuticals and is recorded as completed.

The registry lists enrollment as 125. The primary outcome analysis is defined for all randomized subjects aged 45 to 55 years at baseline, and the outcome-specific groups include 40.0 participants for UNR844-Cl and 38.0 for placebo. Safety records list 62 participants at risk in each group. These are denominators from different posted records; the reason they differ is not reported in the registry record. The posted values should not be treated as though every outcome uses the same analysis population.

The primary endpoint was change from baseline in binocular distance-corrected near visual acuity at Month 3. Secondary outcomes include the number and percentage of subjects in the specified age range who achieved at least 75 ETDRS letters at Month 3, as well as adverse-event reporting. The registry also identifies deaths, serious adverse events, other adverse events, and adverse events leading to study-drug discontinuation as safety categories. The registry record does not report the trial's original sample-size justification, the detailed randomization procedure, allocation concealment, or the precise analysis populations used for each sponsor analysis.

The design makes a randomized group comparison possible, while masking and a placebo comparator are intended design features for limiting some sources of bias. Those design features do not by themselves determine how the analysis handled missing measurements, protocol deviations, or multiple outcomes. Such details are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized subjects aged 45 to 55 years at baseline

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 Binocular Distance-corrected Near Visual Acuity (DCNVA) From Baseline, measured over Baseline and at Month 3.

The primary endpoint is change from baseline in binocular distance-corrected near visual acuity, assessed at Month 3 in subjects aged 45 to 55 years. The measurement was low-contrast DCNVA at 40 cm, using an electronic visual acuity testing system and an ETDRS letter numerical score. Participants were corrected for distance refractive errors during the assessment. The registry describes the unit as the number of letters read correctly.

Change from baseline focuses on how the measured score at follow-up differs from the participant's starting score, rather than on the follow-up score alone. A between-group comparison of average change can describe whether the groups' mean changes differed over the study assessment period. The posted arm estimates are least-squares means: 6.1 letters for UNR844-Cl and 4.5 letters for placebo. The sponsor-reported net mean difference is 1.6 letters.

Near visual acuity is relevant to the study's stated aim of assessing near visual function in people with presbyopia. A letter score provides a numerical measure that can be compared between groups. The registry notes that higher ETDRS scores represent better vision and lower scores represent poorer vision. The endpoint is still a measured visual-acuity outcome, not a complete description of every aspect of near vision or daily functioning. The registry record does not provide a threshold for a clinically important change, so the numerical difference alone cannot establish how important it may be to participants.

7. Results Posted in the Registry

• UNR844-Cl: mean 6.10 versus 4.50 on control; difference 1.60 (95% CI -1.88 to 5.08), standardized effect d = 0.20; z-test p = 0.367.

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.

Number and Percentage of Subjects Aged 45 to 55 Years Achieving 75 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in Binocular DCNVA at Month 3

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • UNR844-Cl: 25.0% (10/40) versus 15.8% (6/38) on control; risk difference 9.2 percentage points (95% CI -8.5 to 26.9), risk ratio 1.58 (0.64–3.93); unadjusted two-proportion z-test p = 0.314.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between UNR844-Cl and the control. The interval gives the range of effects that remain compatible with the data.

The secondary results add context but do not replace the primary endpoint. One concerns the proportion of participants reaching a prespecified ETDRS letter threshold at Month 3; the other set of outcomes concerns adverse events and related safety categories. For the threshold endpoint, the sponsor's reported estimate and the primary result point in a broadly similar direction, but the secondary estimate is imprecise and its reported interval includes the null value. That pattern does not provide strong independent confirmation of a between-group difference.

The threshold analysis and the continuous primary analysis measure related but non-identical aspects of visual acuity. The primary endpoint uses change in the letter score as a continuous measure, retaining information across the range of scores. The threshold endpoint reduces that information to whether a specified score was reached. It can be easier to interpret as a response category, but it discards distinctions between participants who fall on the same side of the threshold and can be sensitive to where the cutoff is set.

Secondary findings generally carry less weight than a prespecified primary analysis because many outcomes can create more opportunities for apparently notable results by chance. Whether the sponsor adjusted for multiple comparisons, or what hierarchy was used for secondary hypotheses, is not reported in the registry record. The registry also does not give a detailed statistical analysis plan explaining how the secondary findings were intended to support or qualify the primary question.

The safety outcomes serve a different purpose from efficacy outcomes: they describe events recorded during the study rather than estimate near-vision change. A lack of serious events in the posted counts does not establish the absence of risk, particularly when event counts are limited and the record does not include uncertainty intervals. The secondary outcomes should therefore be treated as supporting descriptive evidence, with attention to their different definitions, analysis methods, and reporting limitations.

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

• Number and Percentage of Subjects Aged 45 to 55 Years Achieving 75 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in Binocular DCNVA at Month 3
• Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: each participant's change is represented by a numerical letter score, and the analysis compares group averages. The registry reports least-squares mean changes for each arm and describes the sponsor's method as mixed models analysis. Least-squares means are model-based group estimates. A mixed model can account for the structure of repeated or related measurements, depending on the model specification. The precise model terms, covariance structure, and handling of incomplete observations are not reported in the registry record, so the detailed operation of the sponsor's model cannot be reconstructed from the posted result alone.

What does the mean difference represent?

The sponsor reports a net mean difference of 1.6 letters between UNR844-Cl and placebo. It is a contrast between the estimated average changes, expressed in the same letter-score units as the outcome. The posted arm estimates are 6.1 and 4.5 letters. The difference is not a percentage change, a participant-level response rate, or a count of people who improved. It summarizes the group-level mean contrast, and does not imply that every participant experienced the same change.

Why is there also a re-calculated comparison?

The unadjusted re-calculation uses the posted arm summary statistics to estimate a simple difference between group means. It gives the same point estimate of 1.6 letters, an interval from -1.879 to 5.079, and p = 0.367. The standard deviations used for that calculation are approximate, based on the posted standard errors. This is a transparent summary-statistic calculation, not a replacement for the sponsor's mixed model. The sponsor reports a 90% confidence interval from -1.34 to 4.56 and p = 0.183. The two approaches can yield different uncertainty estimates because they use different information and assumptions.

The sponsor's interval describes uncertainty around the model-based estimate under the analysis used for the registry result. A confidence interval is a range of values reasonably compatible with the data and its statistical assumptions. It is not a range that assigns a probability to the fixed, true effect after the data have been observed. When an interval includes zero, the data do not rule out no average difference at the stated confidence level; that does not demonstrate that the true difference is exactly zero.

What does the p-value add?

A p-value measures how incompatible the observed result is with a specified null hypothesis, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor is it a measure of effect size or clinical importance. The sponsor's reported p-value is 0.183; the simple unadjusted re-calculation gives 0.367. The latter is not a second sponsor finding. The registry identifies a two-sided significance level of 0.05 only for the separate planning illustration, not as a reported decision rule for the sponsor's analysis. The analysis decision threshold and any multiplicity adjustment are not reported in the registry record.

General statistical context: standard errors describe the estimated sampling uncertainty of a statistic, while standard deviations describe variation among observations. A standard error can be smaller than the underlying participant-to-participant spread because it concerns uncertainty in an estimate rather than the spread of individual measurements. For the posted arm summaries, the standard errors are 1.24 and 1.27; the re-calculation uses an approximate pooled standard deviation of 7.836. Because that spread is reconstructed approximately, the unadjusted interval and p-value should be treated as approximate as well.

How should a threshold outcome be analyzed?

The secondary threshold outcome classifies participants according to whether they achieved at least 75 ETDRS letters at Month 3. This converts a letter-score measure into a binary outcome: each participant is either counted as meeting the threshold or not. The sponsor reports a Cochran-Mantel-Haenszel odds ratio of 1.9, with a 90% confidence interval from 0.72 to 4.78 and p = 0.283. The registry does not report enough detail to explain any stratification factors used in that analysis. The unadjusted re-calculation uses a risk difference, which is a different effect measure from an odds ratio; it should not be treated as the same estimand or a direct substitute for the sponsor's analysis.

General statistical context: an odds ratio compares odds, whereas a risk difference compares proportions by subtraction. These scales answer related but distinct questions, and their numerical values are not interchangeable. An interval for an odds ratio is interpreted relative to one, while an interval for a difference is interpreted relative to zero. The registry's sponsor-reported interval for the odds ratio includes one, indicating that it is compatible with the null value under that analysis and confidence level.

Details about missing-data methods, analysis populations beyond the stated primary population, model diagnostics, covariate adjustment, and multiplicity procedures are not reported in the registry record. These omissions limit independent assessment of how robust the posted estimates are to alternative analysis choices.

11. Confidence Intervals and Precision

The sponsor-reported primary estimate is a net mean difference of 1.6 letters, with a 90% confidence interval from -1.34 to 4.56. This interval gives a sense of the estimate's precision: the range is broad enough to include a negative difference, no difference, and a positive difference. The point estimate alone therefore does not capture the uncertainty in the trial result. The p-value of 0.183 is consistent with the interval including zero under the sponsor's reported analysis.

The simple unadjusted re-calculation gives an interval from -1.879 to 5.079. It is based on summary statistics and approximate reconstructed variation, rather than the sponsor's mixed-model analysis. Its different width and associated p-value should not be interpreted as evidence that the registry's reported result is incorrect. The two estimates share the same point difference but apply different analytical approaches, and the re-calculated result is not the primary trial analysis.

For the secondary threshold outcome, the sponsor reports an odds ratio of 1.9 with a 90% confidence interval from 0.72 to 4.78. That interval includes the odds-ratio null value of one and spans a wide range of possible associations. The interval therefore does not precisely determine the size of a group difference for this outcome either.

General statistical context: wider intervals indicate less precision, while narrower intervals indicate greater precision, all else being equal. Precision depends on factors such as outcome variability and the amount of information available for an analysis. The registry record does not provide a precision target or clinically important difference for the primary letter-score outcome. Consequently, the intervals describe statistical uncertainty but do not identify which values would matter clinically. The distinction is important: the posted estimates are not exact effects, and the intervals should be considered alongside the study population, endpoint definition, and reporting limitations.

12. Planning a Similar Trial: Sample Size

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

The sample-size figures are planning illustrations, not the trial's original design calculations. For these non-time-to-event outcomes, the figures refer to participants per arm, not a combined total. The planning 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 as a stated fraction of the observed effect. The trial's own original sample-size assumptions and justification are not reported in the registry record.

For the primary continuous outcome, planning for 100% of the observed effect gives 377 participants per arm for 80% power and 505 participants per arm for 90% power. Planning for 75% of the observed effect gives 670 participants per arm for 80% power and 897 participants per arm for 90% power. Planning for 50% of the observed effect gives 1,507 participants per arm for 80% power and 2,017 participants per arm for 90% power.

The 80% power column represents the number of participants per arm estimated to give an 80% chance of detecting the specified effect under the planning assumptions, if that effect is the true effect. The 90% column uses a higher target chance of detection, and therefore gives larger planning figures in the listed rows. Smaller effects need more participants because they are harder to distinguish from random variation. These figures are not observed power, and they do not show the probability that the study's result is true.

The secondary binary outcome has its own planning figures because it uses a different outcome scale and observed effect. Its planning rows likewise increase as the target effect becomes smaller or the desired power becomes higher. The assumptions are illustrations applied to the observed estimates, not evidence that the trial was designed around those assumptions. Actual sample-size planning should be based on a prespecified target effect and appropriate design details, which are not reported in the registry record.

13. How the Sample Size Is Derived

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

Formula

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

Worked calculation for this trial

1. Observed difference Δ = 1.600; pooled standard deviation σ = 7.836.
2. n = 2 × (1.96 + 0.842)² × 7.836² / 1.600² = 376.5, rounded up to 377 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 <- 1.6                      # observed difference in means
sigma <- 7.83580966830453                     # 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(3809611)
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 = 377 (80% power), 505 (90% power)
 75% of observed effect: n per arm = 670 (80% power), 897 (90% power)
 50% of observed effect: n per arm = 1,507 (80% power), 2,017 (90% power)
power.t.test: 377.5 
Simulated power at n = 377 per arm: 0.801 (20000 replicates)

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

14. Analyses Reported by the Sponsor

The sponsor's primary analysis is a mixed models analysis of the net mean difference in change from baseline. It reports a difference of 1.6 letters, a 90% confidence interval from -1.34 to 4.56, and p = 0.183. The simple re-calculation from posted arm summary statistics also gives a mean difference of 1.6 letters, but its approximate interval is -1.879 to 5.079 and its p-value is 0.367.

The matching point estimates are expected because both summaries compare the same posted arm means. The different interval and p-value reflect that the re-calculation is an unadjusted summary-statistic method with an approximate standard deviation, whereas the sponsor reports a mixed-model analysis. Those methods need not produce identical uncertainty estimates. The re-calculation is useful as a check on the arithmetic of the posted means, but it does not reproduce all the information or assumptions in the sponsor's model.

The registry record does not flag a discrepancy between the reported analysis and the recalculation. Accordingly, the sponsor's analysis is the primary reported trial result; the re-calculation should be read as supplementary and approximate. Details needed to replicate the mixed model, including its full specification and missing-data handling, are not reported in the registry record. The secondary endpoint has the same distinction: the sponsor reports an odds ratio using a Cochran-Mantel-Haenszel method, while the re-calculation uses a risk difference. They are different measures, not competing estimates on one identical scale.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary visual-acuity outcome and secondary outcomes, including a threshold-based visual-acuity measure and adverse-event categories. Testing multiple outcomes can increase the chance of at least one apparently unusual result when all are considered without adjustment. A prespecified hierarchy or multiplicity procedure can help define how results should be interpreted, but such a procedure is not reported in the registry record. It is therefore not possible to determine from the posted results whether the reported p-values were adjusted, or whether the secondary analyses were intended as confirmatory or exploratory.

Missing-data handling is also not reported in the registry record. The primary outcome is measured from baseline to Month 3, but the record does not specify the method used if a measurement was unavailable, whether any imputation was used, or how incomplete follow-up was handled in the sponsor's mixed model. Those choices can affect an estimate when the availability of measurements is related to participants' outcomes or treatment assignment. The posted estimates alone do not establish that missingness was absent.

The primary population is described as all randomized subjects aged 45 to 55 years at baseline. The outcome-specific arm counts are 40.0 and 38.0, while the safety groups list 62 at risk in each arm. The registry does not explain the relationship between these denominators or report a full accounting of participants analyzed for each outcome. It also does not state whether the primary analysis followed an intention-to-treat principle or used another analysis population.

The detailed randomization method, allocation concealment, model specification, protocol-deviation rules, and analysis decision threshold for the primary result are not reported in the registry record. The planning illustration includes a two-sided significance level of 0.05, but that is a planning assumption and should not be taken as a documented rule for interpreting the sponsor's hypothesis test. These reporting gaps do not invalidate the posted estimates, but they limit independent evaluation of analysis choices and the role of secondary findings.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists zero serious adverse events in the UNR844-Cl group and zero in the placebo group. Each group has 62 participants at risk in the safety record. The record also lists zero deaths in either group. These are observed counts in the registry record; they do not show that serious events are impossible or that the groups have identical risks.

The registry reports other adverse events for 14 participants in the UNR844-Cl group and 5 in the placebo group. These are not the serious-adverse-event counts. The record does not provide event-level detail in the serious-event list, which is empty, and it does not provide uncertainty intervals for these safety counts. It also does not report enough information to assess the timing, duration, severity distribution, or causal attribution of the other adverse events.

The safety denominators differ from the outcome-specific counts for the primary efficacy analysis, and the reason is not reported in the registry record. Safety counts are descriptive observations from the posted study record; without further detail, they should not be interpreted as a precise comparison or as a complete assessment of potential harms.

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

The registry results show that the posted average change in binocular distance-corrected near visual acuity was 6.1 letters for UNR844-Cl and 4.5 letters for placebo. The sponsor's estimated net difference was 1.6 letters. Its 90% confidence interval extends from -1.34 to 4.56, and p = 0.183. This means that the posted estimate has substantial uncertainty, including values compatible with no difference and values in either direction. The result does not establish a precise treatment effect.

The secondary threshold result is also uncertain, and the safety record contains no reported serious adverse events or deaths in either group. Those observations describe this study's recorded outcomes; they do not establish the effect or safety of treatment in other populations or settings. The record's stated population for the primary question is restricted to randomized subjects aged 45 to 55 years at baseline, and the endpoint is a low-contrast visual acuity test at 40 cm assessed at Month 3.

The primary endpoint is a letter-score measure, not a direct measure of every aspect of near vision, functioning, or participant experience. The registry does not report a minimum clinically important difference, so the numerical estimate cannot by itself establish whether the observed magnitude would matter to participants. Nor does a non-significant p-value demonstrate equivalence, prove there is no effect, or show that the treatment has no effect. It indicates that the data do not provide a sufficiently precise distinction from the null under the reported analysis.

Likewise, a point estimate favoring one group does not prove a benefit. Interpretation should account for the interval, the endpoint and population, and incomplete reporting of analysis details. The posted results offer estimates for this trial; they do not settle broader clinical questions beyond what was measured and reported.

18. Why This Trial Matters Statistically

This trial illustrates why an estimated group difference should be read together with its uncertainty. The primary point estimate is 1.6 letters, but the sponsor's 90% confidence interval ranges from -1.34 to 4.56. Looking only at the point estimate would conceal the range of effects compatible with the reported analysis. The interval communicates that the direction and magnitude remain uncertain.

It also illustrates the distinction between a sponsor's model-based analysis and a simple re-calculation from posted summary statistics. Both give the same point estimate, yet their intervals and p-values differ. A simple re-calculation can help check a summary result, but it cannot reproduce an analysis whose full model details are not reported. Statistical methods are part of the result, not merely a technical afterthought.

The study also includes a continuous primary outcome and a threshold-based secondary outcome. They answer related but different questions. Continuous scores preserve variation across the measure, whereas a threshold focuses on crossing a selected cutoff. The sponsor's methods and uncertainty differ across these analyses, underscoring why estimates should be interpreted on their own scales and not treated as interchangeable.

Finally, the record demonstrates that efficacy and safety summaries can use different denominators and that registry reporting may omit details needed for full independent replication. The sample-size illustrations are not the original design rationale and are not observed power. Keeping these distinctions clear helps readers separate observed estimates, statistical uncertainty, planning calculations, and limitations of the record.

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 trial-specific limitations affect interpretation. The primary result applies to the defined age group of 45 to 55 years at baseline and to a low-contrast binocular acuity assessment at 40 cm at Month 3. The registry record does not establish how the findings relate to other ages, other visual measures, or outcomes beyond that assessment period.

The sponsor's mixed-model result is reported without the full model specification. Covariates, covariance structure, handling of missing values, and analysis-population details beyond the stated primary population are not reported in the registry record. These omissions limit replication and assessment of the sensitivity of the estimate to analysis choices. The outcome-specific sample counts and safety denominators also differ, and the record does not explain why.

The trial's own sample-size justification and original design assumptions are not reported. The planning illustrations use the observed effect and stated assumptions, so they cannot establish whether the original study was adequately planned for a clinically meaningful difference. The registry does not report a minimum clinically important difference for the letter-score endpoint, making clinical interpretation of the estimated magnitude less certain.

The secondary findings require caution because the record does not report a multiplicity procedure or a hierarchy of hypotheses. The adverse-event counts are descriptive and lack uncertainty intervals and detailed event-level context in the record. The study is recorded as Phase 2 and has outcome-specific groups of 40.0 and 38.0 for the primary measure; results from those groups should not be treated as precise estimates of uncommon outcomes. These limitations do not erase the findings, but they constrain how far the posted results can be generalized or interpreted.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of Safety and Efficacy of UNR844 Chloride (UNR844-Cl) Eye Drops in Subjects With Presbyopia. — NCT03809611.
• Registry record last updated 2022-05-11; status last verified 2022-04.
• Results first posted 2020-11-27.
• 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

The registry record describes a completed Phase 2 randomized, double-masked, placebo-controlled, parallel-group study sponsored by Novartis Pharmaceuticals. The intervention was twice-daily 1.5% UNR844-Cl ophthalmic solution, compared with twice-daily placebo ophthalmic solution. Enrollment is listed as 125.

The primary outcome was change from baseline in binocular distance-corrected near visual acuity at Month 3 among randomized subjects aged 45 to 55 years at baseline. The sponsor reported a net mean difference of 1.6 letters, with a 90% confidence interval from -1.34 to 4.56 and p = 0.183. The secondary threshold analysis and safety records provide additional but limited context. Important details about the original sample-size rationale, missing-data handling, multiplicity, and full analysis specifications are not reported in the registry record.