6-Week Proof-of-Concept Study of Travoprost/Brinzolamide Ophthalmic Suspension in Subjects With Open-Angle Glaucoma or Ocular Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 6-Week Proof-of-Concept Study of Travoprost/Brinzolamide Ophthalmic Suspension in Subjects With Open-Angle Glaucoma or Ocular Hypertension (NCT02140060), a randomized phase 2 study. The primary outcome is Mean IOP at Week 6.

2. Clinical Question

The primary outcome was assessed at 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM at Week 6. These repeated measurement times capture IOP at different points during the day, rather than representing a single measurement time. The registry’s outcome description says one eye, designated the study eye, was used for analysis.

The question is therefore about average pressure at several scheduled times after treatment, and how that endpoint was evaluated across the randomized regimens. It is not a report of a single overall treatment contrast: the trial included three fixed-combination dose-level groups as well as component and unfixed-combination comparator groups. The registry record does not report the numerical results at any of the listed times, so it does not support a conclusion about which regimen had a higher or lower mean IOP, or how large any difference was.

3. Trial Design

This was a Phase 2, randomized, double-masked, parallel-group study. The registry lists enrollment of 327 participants and describes the study as a 6-week proof-of-concept evaluation in subjects with open-angle glaucoma or ocular hypertension. The sponsor was Alcon Research. The recorded study start was 2014-06, primary completion was 2014-11, and status is COMPLETED.

Participants were assigned among six treatment groups: TravA/Brinz, TravB/Brinz, TravC/Brinz, AZOPT, TRAV Z, and TRAV Z + AZOPT. The first three were fixed-combination dose-level groups. The registry describes each as receiving the fixed combination twice daily and travoprost solution vehicle once daily at night. AZOPT was brinzolamide 1% ophthalmic suspension twice daily with travoprost solution vehicle at night. TRAV Z was travoprost 0.004% ophthalmic solution once daily at night with brinzolamide suspension vehicle twice daily. TRAV Z + AZOPT combined brinzolamide suspension twice daily with travoprost solution once daily at night. The treatment period was 6 weeks.

Randomization indicates that assignment was determined by a chance-based process, while double masking indicates that the study was described as masked for two parties; the registry record does not specify which parties. A parallel-group design means the trial compared separate groups receiving different regimens, rather than describing a crossover in which participants successively received each regimen. These are general design explanations, not additional details about how the trial was conducted.

The registry does not report the randomization procedure, allocation concealment details, the specific distinctions among dose levels A, B, and C, or the planned sample-size justification. It identifies the study as completed but does not include the dates of every participant’s treatment or follow-up. These omissions limit how fully the conduct and intended precision of the design can be reconstructed from the registry record 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: Of the 327 enrolled, 61 subjects were discontinued prior to randomization. This reporting group includes all randomized subjects (266).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis population includes all subjects who were randomized, received study medication, and completed at least 1 scheduled on-therapy study visit, based upon a last on-therapy carried forward (LOCF) analysis. Here, "n" is the number of subjects with non-missing values at the specific time point for each arm, respectively.

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 subjects who were randomized, received study medication, and completed at least 1 scheduled on-therapy study visit.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Mean IOP at Week 6, measured over Week 6, 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM.

The primary endpoint was mean intraocular pressure (IOP) at Week 6, measured in millimeters of mercury (mmHg). IOP is the fluid pressure inside the eye. The registry says it was measured using Goldmann applanation tonometry and that one eye, called the study eye, was used for analysis. Measurements were scheduled at 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM at Week 6.

The outcome is a continuous measure, and the registry describes its summary as a mean with standard error. In general, a mean describes the average measurement in a group, while a standard error describes the precision of that estimated mean. A standard error is not the same as the spread of individual participants’ measurements. The registry record does not report the group means or standard errors, so their values and precision cannot be described.

The endpoint was selected to assess pressure, which the registry describes as relevant because higher IOP can be a greater risk factor for developing glaucoma or for glaucoma progression leading to optic nerve damage. The stated trial purpose was to evaluate IOP lowering with the fixed combination relative to its components and their unfixed combination. That rationale explains the choice of a pressure endpoint, but it does not establish what the trial found. No numerical endpoint results or between-group estimates are reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a continuous primary outcome: mean IOP in mmHg at Week 6. It says the summary measure is a mean and that dispersion is expressed as a standard error. It also lists six scheduled measurement times at Week 6. No results or statistical analyses are reported, so the methods below explain how these quantities are generally interpreted; they do not identify an analysis model that the trial actually used.

What does a mean describe?

In general, the mean is the arithmetic average of the measurements included in a group summary. It gives a compact description of the group’s measured IOP at a specified time. A mean does not show how individual measurements are distributed around the average. Two groups can have the same mean while having different amounts of individual variation, and a mean alone does not describe the shape of the distribution.

The registry lists measurement times of 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM. These are repeated scheduled assessments at distinct times within the Week 6 visit period. A reader should distinguish a result at one scheduled time from a combined summary across times. The record does not say that the primary measure was an average across all of these times, and it does not report whether separate analyses or a combined analysis were planned. The endpoint title is “Mean IOP at Week 6,” while its timeframe specifies the listed times; the precise way results would be organized across times is not stated in the registry entry.

What does the standard error communicate?

In general, the standard error describes the sampling precision of an estimated mean: it indicates how much the estimate would be expected to vary across repeated samples under the relevant statistical assumptions. It is not a measure of the range or standard deviation of participants’ IOP values. A small standard error can accompany substantial individual variation when the group estimate is based on enough observations; interpretation requires both the estimate and its uncertainty, as well as the analysis context.

A confidence interval is often used to express uncertainty in an estimate over a range of plausible values under specified assumptions. The registry record does not report confidence intervals for the mean IOP or for between-group contrasts. It also does not report the group means or standard errors, so no precision assessment can be reconstructed from the posted endpoint entry.

How should between-group comparisons be understood?

In general, an efficacy comparison requires a clearly defined contrast, such as a difference between the mean outcome in two randomized groups. Its interpretation depends on the estimated difference, its uncertainty, and the analysis plan. The study included three fixed-combination groups and three comparator groups, but the registry entry does not specify which pairwise or other contrasts were designated for formal testing. Nor does it provide adjusted estimates, unadjusted estimates, confidence intervals, or p-values.

When an outcome is measured repeatedly, statistical methods may need to account for the relationship between measurements from the same participant. This is a general consideration, not a statement that this trial used a particular repeated-measures model. The registry record does not identify whether the listed time points were analyzed independently, jointly, or through another approach. It also does not report the handling of any correlation between measurements, or whether any covariates were included in an analysis.

What does randomization add?

In general, random allocation is intended to make treatment groups comparable on average with respect to measured and unmeasured baseline characteristics. It does not guarantee that every characteristic will be balanced in a particular trial. The registry identifies the allocation as randomized but does not give the sequence-generation method, allocation concealment procedure, or baseline outcome summaries. Double masking is recorded, but the registry does not identify the masked parties or explain how masking was maintained. These details therefore cannot be assessed from the registry entry.

The parallel-group structure means that separate randomized groups received the different regimens during the study. Comparisons can be interpreted as between-group comparisons, but their credibility and precision depend on the analysis population, the completeness of outcome data, and the statistical method. The registry specifies some population and missing-data details but does not report the statistical analysis plan or numerical outcomes.

What can be learned from the posted analysis description?

The primary endpoint population included participants who were randomized, received study medication, and completed at least one scheduled on-therapy visit. The registry says the analysis used last on-therapy carried forward (LOCF). In general, LOCF fills a missing later measurement using the participant’s last available on-treatment measurement. This creates an analyzed value rather than leaving the later measurement missing. Its usefulness depends on assumptions about how the outcome would have changed after the last observed value; those assumptions may not reflect the unobserved course.

The record does not report how many measurements were carried forward, why data were missing, or whether the LOCF result was checked against analyses using different missing-data assumptions. It does not report the number of non-missing participants at each measurement time. Therefore, the degree to which the primary outcome analysis depended on carried-forward values cannot be assessed from the registry record.

The registry lists no statistical analyses for the primary outcome. It does not identify a model, a test, a significance threshold for the outcome analysis, or a method for adjusting multiple comparisons. Those details are not reported in the registry record. General explanations of means, standard errors, confidence intervals, repeated measurements, and missing-data methods should not be mistaken for descriptions of methods actually used in this trial beyond the details expressly stated in the registry.

10. Multiplicity, Missing Data and Analysis Populations

The study had one listed primary outcome measure, but IOP was scheduled at 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM at Week 6. It also included six treatment groups, including three fixed-combination dose-level groups and three comparator groups. This creates the possibility of multiple time-specific and between-group comparisons. The registry record does not state which comparisons were prespecified for formal inference, whether a hierarchy was used, or whether any adjustment for multiplicity was planned or performed.

In general, testing many comparisons can increase the chance of obtaining an apparently unusual result by chance if each test is interpreted independently. Methods for controlling that issue depend on the planned family of comparisons and the study’s inferential goals. The registry does not report a multiplicity strategy, statistical analysis plan, or analysis results. It would therefore be inappropriate to infer that the comparisons were adjusted, or that they were not adjusted, from the available entry.

For the primary endpoint, the analysis population included randomized participants who received study medication and completed at least one scheduled on-therapy visit. The outcome description specifies last on-therapy carried forward (LOCF). The record does not report how many participants met this definition at each time point or how many endpoint values were missing. It also does not describe the reasons for missingness, the number of values imputed by LOCF, or sensitivity analyses using alternative assumptions.

The record does not identify an intention-to-treat analysis, a per-protocol analysis, or another analysis population beyond the stated primary-outcome definition. It also does not report a sample-size justification. The sample-size assumptions listed for planning illustrations describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. These are planning assumptions, not evidence of the trial’s original design rationale. No planning-illustration results are reported in the registry record, and the assumptions should not be interpreted as observed power.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina unstable (2.2%), atrial fibrillation (0.3%).

The registry reports serious adverse events separately from other adverse events. In the treatment groups, serious adverse events affected zero participants in TravA/Brinz, zero in TravB/Brinz, zero in TravC/Brinz, one in TRAV Z, zero in AZOPT, and zero in TRAV Z + AZOPT. The numbers at risk listed for those groups were 44, 44, 44, 45, 45, and 44, respectively. These are descriptive counts; the registry does not report a statistical comparison of serious adverse events between groups.

For other adverse events, the registry records 7 participants affected in TravA/Brinz, 11 in TravB/Brinz, 15 in TravC/Brinz, 10 in TRAV Z, 9 in AZOPT, and 13 in TRAV Z + AZOPT. The corresponding numbers at risk were 44, 44, 44, 45, 45, and 44. These counts should not be treated as comparative risks or evidence of differences without a defined analysis and appropriate uncertainty estimates.

The pre-treatment group lists one participant affected by a serious adverse event and one affected by another adverse event, among 327 at risk. This group is reported separately from the treatment arms. Deaths are not reported in the registry record for the individual groups. The serious-event terms listed are “Angina unstable” at 2.2% and “Atrial fibrillation” at 0.3%; the record does not explain the denominator or provide enough detail to connect these percentages to specific treatment groups.

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

This registry entry establishes that the study was designed to compare three travoprost/brinzolamide fixed-combination regimens with brinzolamide alone, travoprost alone, and the unfixed combination. It identifies a clinically relevant measurement—mean IOP at Week 6—and records how the endpoint was measured, when measurements were scheduled, and how the primary-outcome population was defined. It also records adverse-event counts by group.

However, the outcome results needed to interpret comparative efficacy are not reported in the registry record. There are no group means, standard errors, treatment contrasts, confidence intervals, or p-values. Consequently, the record does not show the observed level of IOP in any group, the direction or size of a difference between regimens, or the precision of any such difference. The trial’s stated aim should not be mistaken for a reported finding.

In general, a result from a randomized trial is interpreted by considering the estimated effect and its uncertainty, alongside the design, population, follow-up, and analysis choices. A statistical test alone would not establish the importance of an effect, and a non-significant result would not by itself establish equivalence. Those general principles cannot be applied to a trial-specific conclusion when the estimates and analyses are absent.

The safety counts are also descriptive. They do not establish whether adverse-event rates differed among groups, and the listed group counts are not accompanied by comparative statistical analyses. The short treatment period and the absence of detailed follow-up results also mean that the registry entry does not describe longer-term outcomes. No conclusion about longer-term effects or safety can be drawn from the 6-week study description.

The appropriate reading is therefore limited: the registry records the design and endpoint of a short randomized comparison, together with some adverse-event counts, but it does not report the primary outcome results or formal comparisons. The posted information is insufficient to determine what the study observed about IOP across regimens.

13. Why This Trial Matters Statistically

This trial is statistically notable for its comparison structure. It included three fixed-combination dose-level groups, two single-component groups, and an unfixed-combination group. That arrangement can address different comparative questions, but the registry entry does not identify the planned contrast structure or statistical analysis. Knowing the list of arms is not enough to know which comparison was intended to be primary beyond the stated endpoint.

The endpoint also involves scheduled measurements at several times on the same day. In general, repeated measurements can provide a more detailed description of a time-varying outcome, but they require clarity about whether results are time-specific or combined and how within-participant correlation is handled. The registry lists the times but does not report the analytical approach or results for them. This makes the endpoint description more informative than a single-time-point label, while leaving the inferential plan unclear.

Another important statistical feature is the stated LOCF approach and the selected analysis population. The record says participants had to be randomized, receive medication, and complete at least one scheduled on-therapy visit. In general, outcome conclusions can depend on who is included and how missing measurements are handled. The registry does not report the extent of missing data or analyses under alternative assumptions, so the robustness of the endpoint analysis cannot be evaluated.

Finally, the entry illustrates a distinction between a study’s objective and its reported evidence. The objective is comparative IOP lowering, but the registry does not report outcome estimates or statistical analyses. For statistical interpretation, the absence of those results is consequential: the trial’s design identifies the question, but the available entry does not answer it quantitatively.

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 entry is that it does not report the primary outcome results. It identifies mean IOP at Week 6 as the endpoint and supplies measurement details, but provides no group-specific means, standard errors, or comparative estimates. No confidence intervals or p-values are reported, and the registry lists no statistical analyses. Comparative conclusions about the primary endpoint therefore cannot be made from this record.

The outcome was scheduled at several times at Week 6, but the entry does not explain whether these times were analyzed separately or jointly. It does not report a prespecified comparison hierarchy or a multiplicity strategy. The registry also does not provide the statistical model, covariates, or other analysis specifications. These omissions prevent assessment of how the repeated measurements and multiple treatment groups were handled in inference.

The endpoint population required participants to have received study medication and completed at least one scheduled on-therapy visit, and the record states that LOCF was used. It does not report the number of missing measurements, the reasons for missingness, or the number of values carried forward. Nor does it provide sensitivity analyses that could show whether conclusions changed under other missing-data assumptions.

The registry does not report the sample-size justification or the original power calculation. Its planning assumptions are described as illustrations based on the observed effect, not as the trial’s own design rationale. The record also does not report details of the randomization sequence, allocation concealment, masking procedures, or the distinction among the three dose-level regimens beyond their labels.

Finally, the treatment period was 6 weeks. The entry does not supply longer-term outcome information. Adverse-event counts are descriptive, without statistical comparisons, and deaths are not reported in the registry record for the groups. These limits are specific to the information available in this trial record; they do not establish that the underlying study lacked additional methods or results outside the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: 6-Week Proof-of-Concept Study of Travoprost/Brinzolamide Ophthalmic Suspension in Subjects With Open-Angle Glaucoma or Ocular Hypertension — NCT02140060.
• Registry record last updated 2015-12-29; status last verified 2015-11.
• Results first posted 2015-12-29.
• 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

NCT02140060 is a completed Phase 2 randomized, double-masked, parallel-group proof-of-concept study sponsored by Alcon Research. The registry lists enrollment of 327 participants with open-angle glaucoma or ocular hypertension and a 6-week treatment period.

The trial compared three travoprost/brinzolamide fixed-combination dose-level regimens with brinzolamide, travoprost, and their unfixed combination. Mean IOP at Week 6 was the primary outcome, measured by Goldmann applanation tonometry at scheduled times. The endpoint description specifies a population that received study medication and completed at least one on-therapy visit, with LOCF analysis.

The registry does not report primary-outcome values or statistical analyses. It lists serious and other adverse-event counts by group, but does not report comparative safety analyses. Accordingly, the record describes the study question and design without providing enough outcome information to quantify the primary comparison.