Bioequivalence Study With Clinical Endpoint Comparing Brinzolamide 1% Ophthalmic Suspension to Azopt® 1% Ophthalmic Suspension In the Treatment of Chronic Open Angle Glaucoma or Ocular Hypertension in Both Eyes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bioequivalence Study With Clinical Endpoint Comparing Brinzolamide 1% Ophthalmic Suspension to Azopt® 1% Ophthalmic Suspension In the Treatment of Chronic Open Angle Glaucoma or Ocular Hypertension in Both Eyes (NCT02512042), a randomized phase 3 study. The primary outcome is Mean Difference in Intraocular Pressure (IOP) of Both Eyes Between the Two Treatment Groups at Four Time Points.

2. Clinical Question

The study asks whether brinzolamide 1% ophthalmic suspension manufactured by Indoco Remedies Ltd. For Watson Pharma Pvt Ltd. is bioequivalent to Azopt® 1% ophthalmic suspension from Alcon Laboratories, Inc. The intended population was people with chronic open angle glaucoma or ocular hypertension in both eyes. The primary endpoint was the mean difference in intraocular pressure (IOP) between the treatment groups, assessed at four specified times across Day 14 and Day 42.

The record identifies the study as designed to demonstrate bioequivalence, rather than simply to test whether the treatments differ. That distinction matters: a bioequivalence conclusion ordinarily depends on a prespecified acceptable range for the between-treatment difference and an analysis showing that the uncertainty around the estimate fits within that range. The equivalence margin and numerical endpoint results are not reported in the registry record. Accordingly, the study question can be described, but the posted information does not establish whether the bioequivalence criterion was met.

3. Trial Design

This was a Phase 3, randomized, triple-masked, parallel-group, active-controlled study at multiple clinical trial sites. It compared two ophthalmic suspensions containing brinzolamide at 1% strength: the test product manufactured by Indoco Remedies Ltd. For Watson Pharma Pvt Ltd. and the reference product Azopt® manufactured by Alcon Laboratories, Inc. The registry lists enrollment of 973 and records the study as completed. The start is listed as 2015-04 and primary completion as 2016-04.

Random allocation is intended to reduce systematic differences between groups at the outset. Masking is intended to limit the influence of treatment knowledge on participant experience, clinical care, and outcome assessment. The record labels masking as triple but does not report which roles were masked or how masking was maintained. A parallel-group design assigns participants to one study group rather than having each participant receive both products in sequence. The record describes the comparator as active, meaning that the test product was evaluated against an existing brinzolamide product rather than against no treatment.

The stated purpose was to demonstrate bioequivalence for treatment of chronic open angle glaucoma or ocular hypertension in both eyes. The primary endpoint used measurements at 8:00 am before the morning drop and 10:00 am after the morning drop at Day 14 and Day 42. The endpoint description identifies the Per Protocol Population and refers to eligibility, use of a prespecified proportion of scheduled doses, limits on missed applications, and completion of evaluations at both visits. The full evaluation timing window is not reported in the registry record.

The record does not report the randomization procedure, allocation concealment details, the exact number assigned to each treatment group, or the protocol’s bioequivalence margin. It also does not report a detailed statistical analysis plan. Those omissions limit how fully the design and the intended evidential standard can be evaluated from the registry information alone.

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: The populations for this study included the Randomized Population, Safety Population and Per Protocol Population.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants in Per Protocol Population who met inclusion/exclusion criteria, instilled a pre-specified proportion of the scheduled doses for the specified duration of the study, who did not miss scheduled applications for more than 3 days, and completed evaluations at Day 14 and Day 42 within the visit window.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Mean Difference in Intraocular Pressure (IOP) of Both Eyes Between the Two Treatment Groups at Four Time Points, measured over Day 14 and 42 at 8AM and 10AM.

The primary endpoint is the mean difference in intraocular pressure (IOP) between the two treatment groups, measured in mmHg. IOP is a continuous clinical measure, so the endpoint compares group averages rather than classifying each participant as having or not having an event. The registry specifies measurements in both eyes at 8:00 am, before the morning drop, and at 10:00 am, after the morning drop, on Day 14 and Day 42. These are four assessment times, including measurements before and after the morning dose at each visit.

Repeated assessment at specified times allows the comparison to address IOP at different points in the dosing interval and at more than one study visit. In particular, a before-drop measurement and an after-drop measurement answer different timing questions; they should not be treated as interchangeable observations. The registry describes the endpoint as the mean difference between groups at each specified time, but does not report the group means, standard deviations, treatment differences, confidence intervals, or p-values.

For a bioequivalence study, the purpose of comparing means is not, by itself, to show that a conventional test for any difference is nonsignificant. General statistical context: evidence of equivalence ordinarily requires the estimated difference to be sufficiently precise and to lie within a prespecified acceptable range. The range and the numerical results needed to evaluate it are not reported in the registry record. The endpoint’s clinical and statistical interpretation therefore remains incomplete without those details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome: mean IOP, measured in mmHg, and a comparison of the group means at specified assessment times. General statistical context is useful for understanding what such a comparison can show, but the registry record does not provide the numerical estimates or enough detail to reconstruct the trial’s formal analysis.

What does a mean difference describe?

A mean is a measure of the center of a group’s observations. A difference between two means expresses how far apart the group averages are, with the sign depending on which group is subtracted from which. It does not show how much participants vary around those averages or whether every participant experienced a similar change. The standard deviation, also named as the endpoint’s dispersion measure, describes variation among observations within a group. Neither group’s standard deviation nor the mean differences are reported in the registry record.

Because IOP was assessed at distinct times, each time-specific comparison has its own estimate and uncertainty. Measurements before and after the morning drop represent different points in the dosing schedule, and the Day 14 and Day 42 visits represent different study visits. General statistical context: repeated measurements can be correlated within a participant, so an analysis may need to account for that dependence if it models several measurements together. The registry record does not say whether the analyses were separate at each time or used a joint repeated-measures model.

How should uncertainty be understood?

A confidence interval is a range of values compatible with the observed data under a specified statistical model and confidence procedure. It conveys the precision of an estimate: a narrower interval indicates greater precision than a wider interval, all else equal. For a bioequivalence question, the interval is especially important because the question concerns whether the plausible values for the treatment difference fall within an acceptable range. The registry does not report confidence intervals or the acceptable bioequivalence range, so this reasoning cannot be applied to the trial’s numerical result.

A p-value addresses how surprising data at least as incompatible with a null hypothesis would be under the assumptions of a particular test. General statistical context: a nonsignificant test for a difference does not by itself demonstrate equivalence. A study can fail to detect a difference because the estimate is imprecise, even when the data do not rule out meaningful differences. Conversely, equivalence requires a criterion defined in advance and evidence that satisfies it. The registry record does not report p-values, the test used, or the equivalence criterion.

What does the study design contribute?

Randomization can help balance measured and unmeasured participant characteristics between treatment groups on average, while masking can reduce bias arising from knowledge of treatment assignment. These are general design principles; the registry identifies randomization and triple masking but does not detail the procedures. The parallel-group arrangement compares participants assigned to the test product with participants assigned to the reference product. An active-controlled comparison is consistent with the stated bioequivalence purpose, but the design label alone does not prove that the products met the study’s criterion.

The primary endpoint description specifies a Per Protocol Population. The record describes eligibility requirements, use of a prespecified proportion of scheduled doses, restrictions on missed applications, and completion of Day 14 and Day 42 evaluations. Such restrictions can define the population used for a per-protocol analysis, but the registry record does not report the exact analysis counts, the handling of participants who did not meet the requirements, or whether another population was used in parallel. The full timing window for the required evaluations is also not reported in the registry record.

What can be inferred from the planning illustration?

The planning illustration is described as a calculation based on the observed effect, not as the trial’s original design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration reports participants per arm. These are planning assumptions, not evidence about how the trial was designed or conducted. A sample-size illustration based on an observed effect is not observed power and does not substitute for examining the endpoint estimate and its uncertainty. The registry record does not report the original sample-size justification.

General statistical context: planning calculations depend on assumptions about the effect considered important, variability, significance level, allocation, and desired power. If the assumed effect is smaller, more participants may generally be needed to detect it with the same power, all else equal. This general relationship does not reveal the actual assumptions or analysis plan for this trial. The registry record does not report a trial-specific power target or a detailed sample-size calculation.

Why do the four assessment times matter?

Considering multiple time points can raise a multiplicity question: when several hypotheses are tested, the chance of at least one false-positive finding may increase if no adjustment or prespecified decision rule is used. General statistical context: the impact depends on the testing strategy and the relationship between outcomes. The registry lists four analyses but does not report whether any multiplicity adjustment was applied, whether a hierarchy was used, or how the four results informed the bioequivalence conclusion. No adjustment should be assumed from the available record.

In short, the registry establishes the broad design and outcome structure, but not the details needed to reproduce or fully assess the statistical analysis. Interpretation would require the group-level endpoint summaries, uncertainty estimates, analysis populations and counts, missing-data approach, equivalence margin, and multiplicity strategy. Those items are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is assessed at four times: 8:00 am and 10:00 am on Day 14 and Day 42. Multiple time-specific comparisons create a multiplicity issue if each is tested separately. General statistical context: without an appropriate prespecified strategy, conducting several tests can increase the chance of at least one apparently positive result arising by chance. A strategy might use an adjustment, a hierarchy, or another defined decision rule; the appropriate approach depends on the study’s aims and analysis plan. The registry record does not report whether an adjustment or decision rule was used, or how the four analyses were combined for the bioequivalence conclusion.

Missing-data handling is also not reported in the registry record. The endpoint description refers to a Per Protocol Population that met eligibility requirements, used a prespecified proportion of scheduled doses, did not miss scheduled applications for more than 3 days, and completed evaluations at Day 14 and Day 42. The record does not report how many participants met these criteria, how many measurements were missing, why measurements were missing, or what method was used to handle missing observations.

The record identifies the Per Protocol Population for the primary endpoint but does not report whether an intention-to-treat, modified intention-to-treat, safety, or other analysis population was used. It also does not give group-specific analysis counts at each time point or explain how exclusions were determined. These omissions make it difficult to assess whether the analyzed populations were comparable or how sensitive the primary conclusion might be to population definitions and missing observations.

These are reporting limitations, not evidence that a particular procedure was or was not performed. The protocol or a full statistical report would be needed to establish the analysis plan and its implementation.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 0 serious adverse events for the Generic Brinzolamide 1% Ophthalmic Suspension group, with 489 at risk, and 0 for the Azopt® 1% Ophthalmic Suspension group, with 475 at risk. It also lists other adverse events affecting 55 participants in the generic group and 57 in the Azopt® group. The corresponding at-risk counts are 489 and 475. These are the posted counts; no further calculation or comparison is needed to describe them.

The serious-event entries should be read as registry entries for the reported groups, not as proof that serious events are impossible or that the treatments have identical safety profiles. The record does not provide specific serious adverse-event terms, and deaths are not reported in the registry record. It also does not provide event descriptions, severity details, timing, relatedness assessments, or a fuller account of how adverse events were collected.

The other adverse-event counts are distinct from the serious-event counts. The registry record does not explain the types of events included in that category or whether participants could contribute more than one event. The figures therefore describe the listed safety results but do not, on their own, support broader conclusions about comparative safety.

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

This record documents a completed, randomized, triple-masked, parallel-group comparison of a test brinzolamide 1% ophthalmic suspension with Azopt® 1% ophthalmic suspension. Its stated purpose was to demonstrate bioequivalence for chronic open angle glaucoma or ocular hypertension in both eyes. The endpoint was mean IOP difference between groups at 8:00 am and 10:00 am on Day 14 and Day 42. Those design details clarify what was studied and what question was intended.

They do not reveal the numerical answer. The registry record does not report group means, standard deviations, estimated differences, confidence intervals, or p-values for the primary endpoint. It also does not report the equivalence margin or the statistical decision rule. Without these details, the results cannot be used to determine whether the estimated differences were small enough and precise enough to meet the stated bioequivalence objective.

General statistical context: absence of a reported difference is not the same as evidence of equivalence. An equivalence conclusion depends on the prespecified margin and the uncertainty around the estimated difference, not only on whether a conventional test detects a difference. The posted registry information does not support saying that the products were bioequivalent, nor does it support saying that they were not bioequivalent.

The safety entries are also limited in scope. The registry lists 0 serious adverse events in each group, and other adverse events affecting 55 and 57 participants, respectively. These counts do not replace a detailed safety analysis and do not answer the primary efficacy question. Deaths and specific serious-event terms are not reported in the registry record.

Accordingly, the most defensible reading is that the registry supplies useful information about the trial’s design, population focus, endpoint schedule, and selected adverse-event counts, while leaving the central numerical outcome and key analysis criteria unavailable. A complete interpretation would require the endpoint estimates, their precision, the bioequivalence margin, and supporting details about analysis populations and missing data.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its stated objective is bioequivalence, a question that differs from asking whether two treatments have detectably different average outcomes. The study compares two formulations containing brinzolamide at the same 1% strength, and the primary endpoint is a continuous measure, mean IOP. The intended comparison is therefore centered on the magnitude and precision of between-group differences, evaluated against an acceptable range specified for bioequivalence.

The outcome schedule also raises important design and analysis considerations. IOP was measured before and after the morning drop on Day 14 and Day 42. Those times reflect different positions relative to dosing, and an analysis must make clear how results across the four assessments contribute to the overall conclusion. If separate tests are conducted, multiplicity and the decision rule become relevant. The registry identifies four analyses but does not report how these issues were addressed.

The endpoint population is described as per protocol, with adherence and visit-completion requirements. That makes transparent reporting of exclusions and analysis counts particularly important: a reader needs to know how many participants contributed to each assessment and how missing measurements were handled. These details are not reported in the registry record.

Finally, the study illustrates why a completed trial entry and safety counts alone are not enough to interpret a bioequivalence result. The registry gives useful design context and selected adverse-event information, but not the numerical endpoint estimates, their uncertainty, or the equivalence margin. Those missing elements are central to the statistical question the study was designed to address.

14. 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 principal limitation of the registry information is that it does not report the numerical primary endpoint results. Group means, standard deviations, treatment differences, confidence intervals, and p-values are absent, so neither the magnitude nor precision of the comparison can be evaluated. The equivalence margin and the rule for determining whether the study met its objective are also not reported in the registry record.

The endpoint includes four assessment times, but the registry does not describe how the time-specific analyses were combined or whether multiplicity was addressed. It is therefore not possible to determine what overall pattern was required for a bioequivalence conclusion. The record also does not provide details of the statistical model or whether repeated measurements within participants were analyzed jointly.

The endpoint population is described as Per Protocol, with adherence and visit-completion criteria. However, the number of participants analyzed at each time, exclusions by group, and any additional analysis populations are not reported. Missing-measurement counts, reasons for missingness, and the method used to handle missing data are likewise not reported in the registry record. These gaps limit assessment of the representativeness and robustness of the endpoint analysis.

Other design details are also unavailable, including the randomization procedure, allocation concealment, which roles were masked, and the original sample-size justification. The timing window for the required endpoint visits is not fully reported. The planning illustration is described as based on the observed effect, but it is not the trial’s original design justification and cannot substitute for the missing outcome results.

Safety reporting is limited to the listed counts. Specific serious-event terms and deaths are not reported in the registry record, and further descriptions of event type, timing, severity, and relatedness are absent. These limitations restrict interpretation of both the primary comparison and the safety information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Bioequivalence Study With Clinical Endpoint Comparing Brinzolamide 1% Ophthalmic Suspension to Azopt® 1% Ophthalmic Suspension In the Treatment of Chronic Open Angle Glaucoma or Ocular Hypertension in Both Eyes — NCT02512042.
• Registry record last updated 2020-03-02; status last verified 2020-02.
• Results first posted 2020-03-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a completed Phase 3, randomized, triple-masked, parallel-group, active-controlled study with enrollment of 973. It compares brinzolamide 1% ophthalmic suspension manufactured by Indoco Remedies Ltd. For Watson Pharma Pvt Ltd. with Azopt® 1% ophthalmic suspension manufactured by Alcon Laboratories, Inc. The study’s stated purpose was to demonstrate bioequivalence for chronic open angle glaucoma or ocular hypertension in both eyes.

The primary endpoint is the mean difference in IOP between groups at 8:00 am and 10:00 am on Day 14 and Day 42. The registry record identifies a Per Protocol Population but does not report the numerical endpoint results, equivalence margin, or important analysis details. It lists 0 serious adverse events in each group, with 489 and 475 at risk, and other adverse events affecting 55 and 57 participants, respectively. Deaths and specific serious-event terms are not reported in the registry record.