Assessing the Efficacy and Tolerability of AZARGA® (Brinzolamide 1%/Timolol 0.5% Fixed Combination) as Replacement Therapy in Patients on Brimonidine 0.2%/Timolol 0.5% Fixed Combination Therapy (COMBIGAN®) in Latin America: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessing the Efficacy and Tolerability of AZARGA® (Brinzolamide 1%/Timolol 0.5% Fixed Combination) as Replacement Therapy in Patients on Brimonidine 0.2%/Timolol 0.5% Fixed Combination Therapy (COMBIGAN®) in Latin America (NCT01518244), a na phase 4 study. The primary outcome is Mean Change in Intraocular Pressure (IOP) From Baseline (Prior Therapy) at Week 8.

2. Clinical Question

The study is framed as an assessment of efficacy and tolerability in Latin America. Its clinical question is therefore about the pressure change observed after a treatment switch in the enrolled group, rather than a direct estimate of how AZARGA® compares with a concurrent control. The registry describes IOP as fluid pressure inside the eye and identifies Goldmann applanation tonometry as the measurement method. It also states that one eye was selected as the study eye and that only study-eye data were used for the efficacy analysis.

A more negative change represents a greater reduction from baseline, according to the outcome description. That direction helps explain how the endpoint is interpreted, but it does not establish what change occurred. Numerical results for the mean change and its variability are not reported in the registry record. The record also gives a secondary question—whether participants reached target IOP of 18 mmHg or lower at Week 8—but does not report its numerical result.

3. Trial Design

This was a completed Phase 4, single-group study sponsored by Alcon Research. The registry lists an enrollment of 50 and gives the study start as 2011-12 and primary completion as 2013-02. The stated purpose was to assess efficacy and tolerability after changing participants from prior COMBIGAN® pharmacotherapy to AZARGA®.

The intervention was brinzolamide/timolol maleate fixed combination, identified as AZARGA®. Participants self-administered 1 drop in the study eye or eyes twice a day for 8 weeks. The record identifies open-angle glaucoma or ocular hypertension as the conditions under study. It does not provide further eligibility details, participant characteristics, or information about how many participants completed follow-up.

The design is listed as single-group, with allocation recorded as NA and masking recorded as none. No concurrent control arm is described. The comparison underlying the primary outcome is within participants: IOP at baseline, while on prior therapy, is compared with IOP at Week 8 after the switch. Because the registry does not describe random allocation or a like-for-like control group, the result cannot be read as a randomized between-treatment contrast.

The primary endpoint is mean change in IOP from baseline on prior therapy to Week 8. The record says that Goldmann applanation tonometry was used and that one study eye was selected for efficacy analysis. The primary analysis population includes participants who received AZARGA® and had at least 1 on-therapy study visit, V2 or V3. The record does not report the number meeting that analysis-population definition.

A secondary outcome was the percentage of participants who reached target IOP of 18 mmHg or lower at Week 8. Although the registry identifies two outcome measures, it lists no analyses. Numerical outcome estimates, variability estimates, and inferential results 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 participants who received at least one dose of AZARGA®.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population includes all participants who received AZARGA® and with at least 1 on-therapy study visit (V2 or V3).

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: The analysis population includes all participants who received AZARGA® and with at least one on-therapy study visit (V2 or V3). Of the 50 enrolled, 1 participant discontinued after V1 and before V2.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in Intraocular Pressure (IOP) From Baseline (Prior Therapy) at Week 8, measured over Baseline, Week 8.

The primary endpoint is mean change in intraocular pressure (IOP) from baseline, measured while participants were on prior therapy, to Week 8 after changing to AZARGA®. IOP is described in the registry as fluid pressure inside the eye and is measured in millimeters of mercury (mmHg). The specified method is Goldmann applanation tonometry. For the efficacy analysis, the registry says one eye was selected as the study eye and only measurements from that eye were used.

Change from baseline gives a within-participant description of how the measured pressure differs between the two specified time points. The registry defines more negative change as a greater amount of improvement. This direction is important when interpreting a mean change, but the record does not report the mean, standard deviation, confidence interval, or other numerical estimate for this endpoint. Therefore, the direction and magnitude of the observed group result cannot be determined from the registry record.

IOP is used as an endpoint because the record identifies higher IOP as potentially representing greater risk of glaucoma development or progression, with possible optic nerve damage. That rationale explains why pressure is measured; it does not make a pressure change equivalent to a demonstrated change in disease progression. The secondary endpoint asks whether participants reached the stated target of 18 mmHg or lower at Week 8, but its numerical result is also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measure: change in IOP, expressed in mmHg. The registry specifies the mean as the summary measure and standard deviation as the measure of dispersion. The mean describes the average change among the participants included in the analysis. The standard deviation describes how spread out individual changes are around that average. Neither value is reported numerically in the registry record, so the observed average and the variation across participants cannot be assessed.

What does a change score represent?

A change score compares a participant’s measurement at a later time point with that participant’s baseline measurement. Here, baseline refers to IOP while the participant was receiving prior therapy, and the later assessment is at Week 8 after the switch to AZARGA®. The registry states that a more negative change indicates a greater amount of improvement. General statistical explanation: a mean change summarizes the average within-participant movement, but it does not show whether every participant changed in the same direction. Individual results and the distribution of changes would be needed to examine that pattern.

The registry identifies Goldmann applanation tonometry as the measurement method. It specifies that one eye was chosen as the study eye and only data from that eye were used for the efficacy analysis. This means the primary efficacy result is not described as an average across both eyes. The record does not report the rule used to select the study eye or provide measurement-level data, so further details about selection or measurement variability are not available.

How should dispersion and precision be understood?

Standard deviation describes variability among individual measurements or changes; it is not itself a measure of the precision of the estimated mean. General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity, with a range of values compatible with the data under the method’s assumptions. A narrow interval would generally indicate greater precision than a wide interval, but no confidence interval for the primary outcome is reported in the registry record. There is therefore no basis for describing the precision of the estimated mean change.

General statistical explanation: the mean and standard deviation are useful summaries for continuous outcomes when the mean is a suitable description of the data. If observations are unusually skewed or dominated by extreme values, the mean and standard deviation may not convey the full distribution. The registry does not report the distribution of individual IOP changes, diagnostic checks, or alternative summaries, so those features cannot be evaluated.

What does the design permit statistically?

This is a single-group study, not a randomized comparison. The primary contrast is between baseline on prior therapy and Week 8 after the treatment switch. General statistical explanation: a within-participant comparison can account for stable differences between people when describing change, because each participant contributes measurements at both times. It still cannot distinguish the effect of the treatment switch from other time-related influences without a concurrent comparator. The registry record does not describe a control group or a randomized allocation process.

The registry records allocation as NA and masking as none. These entries do not supply additional detail about the conduct of outcome assessment or other safeguards against bias. The statistical analysis plan, including any adjustment for baseline values or other covariates, is not reported in the registry record. No hypothesis test, p-value, confidence interval, or model specification is reported for the primary outcome.

How should planning illustrations be read?

The planning illustration is described as based on the observed effect and as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers an effect to detect expressed as a stated fraction of the observed effect. These are planning assumptions for a hypothetical two-arm calculation, not a description of the single-group study’s actual design. The illustration is not observed power and does not establish what effect the study could reliably detect. The numerical effect estimate and planning counts are not reported in the registry record, so they cannot be interpreted.

General statistical explanation: a sample-size calculation is conditional on its assumptions, such as the effect size, variability, significance level, allocation, and analysis method. If those assumptions differ from a completed study’s actual design or data, the calculation does not describe the study’s achieved precision. It also cannot substitute for an observed treatment-effect estimate or an interval quantifying uncertainty.

The secondary endpoint is a proportion: the percentage of participants who reached target IOP of 18 mmHg or lower at Week 8. General statistical explanation: a proportion requires a clearly defined denominator and an observed count of participants meeting the criterion. The registry identifies the endpoint but does not report its numerical result or its analysis. The record therefore does not permit an assessment of the estimated percentage or its uncertainty.

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(49)
m   <- c(-3.6)
sp  <- c(3.01)
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®  49  -3.600  3.010  -4.465  -2.735

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies two outcome measures: the primary mean change in IOP from baseline to Week 8 and the secondary percentage of participants reaching target IOP of 18 mmHg or lower at Week 8. It reports zero analyses. No statistical analysis plan, hierarchy of testing, adjustment for multiple comparisons, or inferential results are reported in the registry record. It is therefore not possible to determine whether formal hypothesis testing was planned or how multiplicity was handled.

General statistical explanation: when several outcomes or comparisons are tested, the chance of a false-positive finding can increase if the tests are interpreted without accounting for their number or prespecified hierarchy. This is relevant as a general consideration, not a claim that this study performed multiple tests. The registry does not report enough analysis detail to determine whether such procedures were used.

The primary analysis population is defined as participants who received AZARGA® and had at least 1 on-therapy study visit, V2 or V3. The number who met this definition is not reported in the registry record. Nor does the record state how many participants had a Week 8 IOP measurement, how many were excluded from the analysis, or why any data may have been unavailable.

Missing-data methods, including any imputation, are not reported in the registry record. The record also does not describe whether analyses included all enrolled participants, how incomplete follow-up was handled, or whether sensitivity analyses were conducted. These omissions limit assessment of the analysis denominator and of the potential influence of missing measurements. The enrollment of 50 should not be assumed to equal the number included in the primary analysis.

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 non-serious adverse event terms

The registry reports safety counts for the AZARGA® group. For serious adverse events, 50 participants were listed as at risk and 0 as affected. For other adverse events, 50 were listed as at risk and 4 as affected. These are participant counts in the registry entry, not a count of the total number of event episodes. The registry does not list serious adverse-event terms, and the specific other adverse-event terms are not reported in the registry record.

The death field contains no numerical value. That is different from a reported count of zero, so the number of deaths is not reported in the registry record. The safety entry also does not provide event timing, duration, severity details for the other events, or attribution to AZARGA®. The figures therefore describe the posted counts but do not provide a detailed account of the events or their circumstances.

General statistical explanation: a count of affected participants is descriptive. It does not, by itself, establish whether an event was caused by treatment or allow a comparison with another therapy. In this study record, there is no concurrent comparator group for interpreting differences in safety outcomes.

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

The registry record describes a completed, single-group study evaluating a switch from prior COMBIGAN® therapy to AZARGA® in participants with open-angle glaucoma or ocular hypertension. It identifies mean IOP change from baseline on prior therapy to Week 8 as the primary outcome and gives the direction of interpretation: more negative change means a greater reduction. It also identifies a Week 8 target-IOP outcome and reports safety counts for the AZARGA® group.

However, numerical results for the primary and secondary efficacy outcomes are not reported in the registry record. The mean change, its standard deviation, and any confidence interval or test result are absent. The record therefore does not establish the size, direction, or precision of the observed group change. The target-IOP percentage is also not available, so that outcome cannot be characterized from the registry information.

The design also determines what an observed change could mean. This is not a randomized comparison with a concurrent control group. General statistical explanation: a before-and-after change can describe what happened between two time points, but it does not by itself isolate the effect of the treatment switch from other influences that may occur over time. The registry record does not support a causal comparison between AZARGA® and COMBIGAN®.

The safety entries report 0 participants affected by serious adverse events among 50 at risk and 4 affected by other adverse events among 50 at risk. Those entries do not identify the specific other events, and the death result is not reported. They should be understood as the available descriptive counts, not as a complete account of safety or a comparison across treatments.

In short, the record communicates the study question, treatment regimen, endpoint definitions, and some safety counts. It does not report the numerical efficacy findings needed to quantify the IOP change, nor does its single-group design provide a randomized treatment contrast. No conclusion about comparative efficacy or treatment effect can be drawn from the reported registry information.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why design and outcome reporting matter alongside the choice of endpoint. The registry specifies a clinically relevant continuous measurement, its timing, the measurement method, and the intended analysis population. It also clarifies the direction of the change score, so readers can understand what a negative value would mean if an estimate were reported.

At the same time, the numerical primary outcome is not reported in the registry record. Without the mean change and its dispersion, the result cannot be described in magnitude or precision. The same issue applies to the secondary target-IOP outcome: its definition is present, but its numerical result is not. This illustrates the difference between knowing what a study intended to measure and being able to evaluate what it observed.

The single-group replacement design is another important statistical feature. A baseline-to-Week 8 comparison can describe change in the analyzed participants, but it is not a randomized comparison against a concurrent treatment group. General statistical explanation: design controls what conclusions the data can support; an endpoint’s clinical relevance does not remove limitations created by the absence of a comparator.

The registry also distinguishes enrollment from the defined primary analysis population. Although enrollment is 50, the analysis population requires receipt of AZARGA® and at least 1 on-therapy study visit, and its size is not reported. This makes transparent reporting of participant flow and missing outcome data especially important for judging how representative the analysis may be.

Finally, the safety counts are reported with participant denominators, while event terms and the death result are unavailable. This emphasizes why counts need context: definitions, event descriptions, and complete reporting are necessary for interpretation. Collectively, these features make the record a useful illustration of how endpoint definition, study design, completeness of results, and transparent analysis reporting all shape statistical interpretation.

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 interpreting efficacy is that numerical results for both the primary and secondary outcomes are not reported in the registry record. The primary outcome’s mean change and standard deviation are named, but no estimate, confidence interval, or test result is available. The secondary outcome is defined as the percentage reaching target IOP of 18 mmHg or lower at Week 8, but its result is also absent.

The study has a single-group design and no concurrent comparator is described. The baseline value was measured while participants were on prior therapy, whereas the later value was assessed after the switch to AZARGA®. General statistical explanation: such a before-and-after design cannot separate the effects of the change in therapy from other changes over time. The record therefore does not support a randomized comparative estimate.

The registry lists enrollment of 50, but does not report the number included in the primary analysis or the number with Week 8 outcome data. The analysis population definition requires participants to have received AZARGA® and attended at least 1 on-therapy study visit, V2 or V3. Missing-data handling and reasons for unavailable measurements are not reported in the registry record, limiting assessment of attrition and analysis completeness.

The statistical analysis plan, model details, hypothesis-testing procedures, and handling of multiple outcomes are not reported. No numerical confidence interval or other precision measure is available. The record also does not provide participant characteristics or further eligibility details, which limits assessment of how closely the enrolled group can be described.

Safety reporting is limited to participant counts. Specific terms for the other adverse events are not reported, the serious-event term list is empty, and the death result is not reported. These gaps prevent a detailed description of the safety observations. The planning assumptions describe a hypothetical equal-allocation calculation, not the actual single-group design, and cannot replace missing observed outcome results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessing the Efficacy and Tolerability of AZARGA® (Brinzolamide 1%/Timolol 0.5% Fixed Combination) as Replacement Therapy in Patients on Brimonidine 0.2%/Timolol 0.5% Fixed Combination Therapy (COMBIGAN®) in Latin America — NCT01518244.
• Registry record last updated 2015-08-07; status last verified 2014-02.
• Results first posted 2014-04-04.
• 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

NCT01518244 is a completed Phase 4, single-group study sponsored by Alcon Research, with enrollment listed as 50. It assessed AZARGA® as replacement therapy for participants previously receiving COMBIGAN® for open-angle glaucoma or ocular hypertension. The AZARGA® regimen was 1 drop in the study eye or eyes twice a day for 8 weeks.

The primary outcome was mean change in IOP from baseline on prior therapy to Week 8, measured by Goldmann applanation tonometry. The primary analysis population was participants who received AZARGA® and had at least 1 on-therapy study visit, V2 or V3. The registry also lists the percentage reaching target IOP of 18 mmHg or lower at Week 8.

Numerical efficacy results and analysis details are not reported in the registry record. Safety entries list 0 serious adverse-event-affected participants and 4 participants affected by other adverse events, each among 50 at risk; the death result is not reported.