Safety and Efficacy of Adding AZARGA® Adjunctive to Prostaglandin Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Adding AZARGA® Adjunctive to Prostaglandin Therapy (NCT01263444), a na phase 4 study. The primary outcome is Mean Change From Baseline in Intraocular Pressure (IOP) at Week 12.

2. Clinical Question

3. Trial Design

This was a Phase 4, completed, single-group study sponsored by Alcon Research. The registry lists an enrollment of 47. The study started in 2011-03, and primary completion was in 2013-04. Allocation is listed as NA, and masking as none. These design features mean the record does not describe random assignment to different treatment groups or masking of treatment assignment.

Participants received brinzolamide 1% / timolol 0.5% fixed combination as an addition to their habitual prostaglandin monotherapy. The study description specifies administration to the study eye or eyes twice a day for 12 weeks, with the added medication separated from the habitual prostaglandin by a 5 minute interval. The primary outcome timeframe is baseline and Week 12.

A single-group design can describe measurements over time among participants receiving the study regimen, but it does not create a contemporaneous untreated or alternative-treatment group. A change from baseline therefore cannot, on its own, separate change associated with the regimen from other explanations such as natural fluctuation, measurement variability, or changes in circumstances during follow-up. The registry record does not report further protocol details that would clarify how those issues were addressed.

The listed outcome measures include the primary Week 12 mean IOP change, change at Week 4, mean change at Week 12 by prostaglandin group, and the percentage reaching a target IOP of 18 mmHg or lower. Results for these outcomes 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.

Before assignment: This reporting group includes all enrolled participants (47).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis population includes all patients who received study medication and had at least one on-therapy study visit minus missing responses and/or visit attendance.

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: This analysis population includes all enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Intraocular Pressure (IOP) at Week 12, measured over Baseline, Week 12.

The primary endpoint is mean change from baseline in intraocular pressure at Week 12, measured in mmHg. IOP is the fluid pressure inside the eye. The registry description identifies Goldmann applanation tonometry as the measurement method and states that only one eye, designated the study eye, contributed to the mean. A higher IOP can be a greater risk for developing glaucoma or glaucoma progression leading to optic nerve damage.

Change from baseline expresses how the measured value at follow-up differs from the participant’s starting measurement. The endpoint is a mean, so it describes the average change in the analysis population rather than the experience of every individual participant. The record states that a more negative change indicates a greater amount of improvement. That direction convention helps interpret a reported estimate, but the registry record does not give the Week 12 mean change or its standard deviation.

IOP is used as a measurable clinical outcome relevant to the conditions named in the record. However, a change in this measure is not by itself a complete account of clinical benefit, safety, or longer-term outcomes. The record does not report a numerical endpoint estimate, confidence interval, or statistical test result for the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

General: for a continuous outcome such as IOP, a mean change summarizes the average of participants’ follow-up values relative to their baseline values. It gives a compact description of the group’s average trajectory, but it does not show how much participants varied or whether a similar change occurred for each person. The record specifies that only the study eye contributed to the primary mean. The registry record does not report the mean change itself or its standard deviation, so neither the average magnitude nor the spread of individual changes can be assessed.

The direction convention matters: the record says that a more negative change indicates a greater amount of improvement. A reader should interpret the sign of any reported estimate using that convention. It does not replace examination of the estimate’s uncertainty or the study design.

What would a confidence interval add?

General: a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions used to calculate it. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The interval does not remove design limitations, and it is not a guarantee that the true value lies within its limits. No confidence interval for the primary endpoint is reported in the registry record.

For a single-group change analysis, uncertainty may reflect variation in participant measurements and the size of the analysis population, among other factors. An interval around a within-group change would describe uncertainty in that change estimate; it would not supply the missing concurrent control needed to make a randomized between-group comparison.

What is the role of a statistical test?

General: a statistical test assesses how compatible the observed data are with a specified null hypothesis under a particular model. A p-value is not a measure of effect size, clinical importance, or the probability that a treatment works. Its interpretation depends on the analysis plan, the data, and assumptions. The registry record lists no statistical analyses and does not report a p-value or the test used for the primary endpoint. The test hypothesis and its implementation are therefore not reported in the registry record.

The sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of the observed effect. Those are planning assumptions, not a description of this single-group study’s allocation. The record does not report the resulting participant requirements, nor does it report a trial-specific sample-size justification. A planning calculation is not observed power and does not establish the precision achieved by the completed study.

Why does over-dispersion matter in general?

General: over-dispersion occurs when the observed variability is greater than a statistical model assumes. If a model understates variability, standard errors can be too small and intervals too narrow, making results appear more precise than they are. Appropriate handling depends on the outcome and model. The primary measure in this record is a continuous mean, and the registry record does not describe a statistical model or report analyses that would allow an assessment of over-dispersion. No particular over-dispersion adjustment should be inferred.

For continuous data, the reported standard deviation helps describe variation among observations, while the standard error concerns uncertainty in an estimated mean. These quantities answer different questions. The primary endpoint lists standard deviation as its dispersion measure, but the numerical standard deviation and the endpoint mean are not reported in the registry record. Without those values and the analysis details, readers cannot reconstruct the endpoint’s precision or verify an analysis.

What can a baseline comparison establish?

General: comparing follow-up with baseline uses each participant’s starting measurement as a reference. This can be useful for describing within-participant change, but it is not equivalent to comparing randomized treatment groups. In a single-group study, the baseline value does not represent what would have happened over the same period without the added regimen. Thus, even a precisely estimated change would remain a within-group finding and would not by itself establish a causal treatment effect.

The registry record names no analysis method beyond the mean and standard deviation description of the primary outcome. Details such as covariate adjustment, handling of repeated measurements, confidence-interval construction, and the precise statistical test are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Azarga")
n   <- c(47)
m   <- c(-6)
sp  <- c(3.2)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Azarga  47  -6.000  3.200  -6.940  -5.060

11. Multiplicity, Missing Data and Analysis Populations

The record lists a primary outcome and three secondary outcomes: mean IOP change at Week 4, mean change at Week 12 by prostaglandin group, and the percentage reaching a target IOP of 18 mmHg or lower. Considering multiple outcomes can increase the chance of obtaining a statistically notable result by chance if each is tested separately. General: multiplicity procedures can control that risk, but the appropriate method depends on the prespecified testing strategy and the purpose of the analyses. Any multiplicity adjustment is not reported in the registry record.

The registry lists four outcome measures and no statistical analyses. It does not report an analysis hierarchy, a family of hypotheses, a multiplicity adjustment, or whether secondary outcomes were treated as exploratory. Numerical results and statistical tests for the primary and secondary outcomes are not reported in the registry record.

The primary analysis population is defined as patients who received study medication and had at least one on-therapy study visit, minus missing responses and/or visit attendance. This description indicates that the analysis was not simply defined as everyone enrolled, but the registry record does not report the number included in the primary analysis or the number excluded.

The extent and pattern of missing data, reasons for missingness, and methods used to handle missing measurements are not reported in the registry record. General: missingness can affect an estimate if participants with unobserved outcomes differ from those whose outcomes are observed. Without counts and handling details, it is not possible to judge the direction or potential size of that concern. The record also does not report whether any sensitivity analyses were conducted.

12. Safety Results

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

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

Serious events with the highest arm-level rate: pseudo stenocardia (2.1%).

For the Azarga group, the registry lists 47 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it lists 47 participants at risk and 0 affected. These figures describe the recorded counts in the registry; they do not by themselves establish whether an event was caused by study medication.

The registry lists “Pseudo stenocardia” among the top serious terms, with 2.1%. The record does not provide enough detail to reconcile that term-level percentage with the aggregate serious-event count or to determine the event’s clinical circumstances. Deaths are not reported in the registry record.

General: an adverse-event count is interpreted in relation to the population observed, the period of observation, event definitions, and completeness of reporting. Counts in a single group cannot provide a controlled comparison of risks. The registry record does not report further comparative safety analyses, detailed event narratives, or a causal assessment. These figures should therefore be read as descriptive registry counts, not as proof of either causation or absence of risk.

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

The record describes a study of adding a brinzolamide/timolol fixed combination to habitual prostaglandin monotherapy and identifies Week 12 mean change in study-eye IOP as the primary endpoint. It provides the measurement method, the analysis-population definition, and the direction used to interpret change. Those details clarify what the study intended to measure.

What the registry record does not report is the primary endpoint result. Without the numerical mean change, its standard deviation, and an uncertainty estimate, readers cannot determine how large the observed average change was or how precisely it was estimated. The listed secondary outcomes also lack numerical results in the registry record. Accordingly, the record does not support a conclusion about the observed size of change or its statistical significance.

Even if a within-group change estimate were available, the single-group, unmasked design would limit causal interpretation. There is no concurrent randomized control group against which to compare the change over the same period. A baseline measurement is useful for describing change, but it cannot alone show what would have happened without the added medication.

General: statistical significance and clinical importance are distinct questions. Statistical evidence concerns compatibility with a model and its assumptions; clinical importance requires context about the outcome and the size of a change. Neither question can be settled without the reported estimate and appropriate context. The record’s endpoint description explains why IOP was measured, but does not substitute for outcome data.

The safety counts are also descriptive. They report one serious adverse event among 47 at risk and no other adverse events among 47 at risk, alongside a listed serious-event term. Without a comparative group and fuller reporting context, those counts do not establish the cause of events or characterize comparative risk. The appropriate reading is limited to what the registry records, while recognizing the important outcome and design details that are not reported.

14. Why This Trial Matters Statistically

This study is statistically instructive because it pairs a clearly defined continuous endpoint with a design that calls for careful limits on interpretation. Mean change in IOP from baseline to Week 12 is understandable as a description of change, and the record specifies the measurement instrument and study eye. But the design is single-group, so a within-participant comparison is not a randomized contrast between treatment strategies.

The record also illustrates why endpoint definitions and outcome results are different kinds of information. Knowing the measure, timeframe, unit, direction convention, and analysis population makes the intended analysis clearer. It does not reveal the observed mean, the variability, the precision, or the statistical evidence. Those numerical results are not reported in the registry record.

The enrollment of 47 and the analysis-population description raise a further reporting issue: enrollment does not tell readers how many observations contributed to the primary analysis. Without analysis counts and missing-data details, the relationship between the enrolled group and the analyzed group cannot be evaluated.

Finally, the record lists several outcomes but does not report analyses or a multiplicity approach. This demonstrates why interpretation of multiple endpoints depends on knowing which questions were prespecified and how results were analyzed. General statistical principles can explain these concerns, but they cannot fill gaps in the trial record. The distinction between a descriptive change, a causal comparison, and the precision of an estimate is central to reading single-group clinical data responsibly.

15. 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 main limitation for interpretation is that numerical results for the primary endpoint are not reported in the registry record. The record also does not report the standard deviation, confidence interval, p-value, or statistical test result. The magnitude, variability, and precision of the Week 12 mean change therefore cannot be assessed.

The study is listed as single-group, with allocation NA and no masking. There is no concurrent randomized comparator in the record, limiting the ability to attribute a change from baseline specifically to the added regimen. Enrollment is listed as 47, but the number analyzed for the primary endpoint is not reported in the registry record.

The analysis-population description excludes missing responses and/or visit attendance, but the number and pattern of missing observations and the method used to handle them are not reported. Statistical methods beyond the mean and standard deviation description are also not reported. The registry record does not state whether any adjustment for multiple outcomes or sensitivity analyses were used.

The listed safety counts are descriptive and lack a concurrent comparison. Deaths are not reported in the registry record, and the record does not provide fuller event details or causal assessments. The study duration for administration is described as 12 weeks, so longer-term outcomes are not established by the information in the record. These reporting and design limitations constrain what can be concluded from the registry entry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of Adding AZARGA® Adjunctive to Prostaglandin Therapy — NCT01263444.
• Registry record last updated 2014-05-20; status last verified 2014-05.
• Results first posted 2014-05-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01263444 is a completed Phase 4, single-group study sponsored by Alcon Research, with enrollment of 47. It evaluated adding brinzolamide 1% / timolol 0.5% fixed combination to habitual prostaglandin monotherapy in patients with ocular hypertension or primary open-angle glaucoma. The regimen description specifies one drop in the study eye or eyes twice a day for 12 weeks.

The primary endpoint was mean change from baseline in study-eye IOP at Week 12, measured by Goldmann applanation tonometry. The registry record does not report the numerical primary endpoint result or its precision. It lists one serious adverse event among 47 at risk and zero other adverse events among 47 at risk; deaths are not reported in the registry record. The absence of a concurrent control group, outcome estimates, and analysis details limits interpretation of both efficacy and safety findings.