This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Safety and Efficacy Study of Fixed-Combination Bimatoprost and Brimonidine in Chronic Glaucoma or Ocular Hypertension (NCT01863953), a randomized phase 2 study. The primary outcome is Change From Baseline in Average Eye Mean Diurnal Intraocular Pressure (IOP).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01863953 |
| Phase | Phase 2 |
| Condition | Glaucoma, Ocular Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 112 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Allergan |
| Results posted | Yes |
2. Clinical Question
Population
Patients with chronic glaucoma or ocular hypertension were eligible. The primary endpoint population was the Modified Intent to Treat group: randomized and treated patients with baseline and at least one postbaseline intraocular pressure assessment. The registry record does not report further eligibility details or the number included in this population.
Intervention
The intervention was fixed-combination bimatoprost and brimonidine, given as one drop in each eye twice daily for 6 weeks.
Comparator
The record describes two comparator regimens: bimatoprost ophthalmic solution 0.01% in the evening with vehicle in the morning, and brimonidine tartrate ophthalmic solution 0.2% twice daily. Each regimen was given as one drop in each eye for 6 weeks.
Primary question
The primary endpoint was change from baseline in average-eye mean diurnal intraocular pressure, measured at Baseline and Day 42. The registry record does not report the treatment-group changes, a between-group estimate, or an analysis of this endpoint. It therefore does not establish from the posted results whether the regimens differed on the primary measure, or how precisely any difference was estimated.
Intraocular pressure is fluid pressure inside the eye. For this endpoint, the average-eye measure uses the average of right- and left-eye pressure, then averages readings taken at hours 0, 2, 4, 8 and 12. A negative change from baseline indicates a reduction in pressure; a positive change indicates an increase. These definitions describe the outcome, not a finding about any treatment.
The registry lists change from baseline in average-eye mean diurnal IOP and average-eye mean diurnal IOP as secondary outcomes. It does not report their results. The stated comparison is among three treatment regimens, but the registry record does not give a reported primary-effect estimate or a statistical test addressing those comparisons.
3. Trial Design
This was a randomized, double-masked, parallel-group Phase 2 study sponsored by Allergan. The registry lists an enrollment of 112 and describes the study as completed. The start and primary-completion dates are recorded as 2013-06 and 2013-12. The brief description identifies the study as an evaluation of the safety and efficacy of fixed-combination bimatoprost and brimonidine compared with LUMIGAN® and ALPHAGAN® in patients with chronic glaucoma or ocular hypertension.
The intervention groups were the fixed combination, bimatoprost ophthalmic solution 0.01% with vehicle, and brimonidine tartrate ophthalmic solution 0.2%. In the fixed-combination and brimonidine groups, the specified regimen was one drop in each eye twice daily for 6 weeks. In the bimatoprost-and-vehicle group, bimatoprost was used in the evening and vehicle in the morning, with one drop in each eye daily for 6 weeks. The registry does not provide further administration or adherence details.
Randomization assigns treatment according to a chance-based process, which is intended to reduce systematic differences between groups at the outset. In a parallel design, participants remain assigned to their treatment group rather than switching among the study regimens. Double masking means that the record identifies the trial as masked at two levels, but it does not specify which roles were masked or how masking was maintained.
The registry record does not report the allocation procedure, whether allocation was concealed, or the planned statistical analysis. It also does not give a sample-size justification. The record’s sample-size assumptions describe a planning illustration based on an observed effect; those assumptions should not be interpreted as the trial’s own design rationale or as evidence about the strength of its findings.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Fixed-Combination Bimatoprost/Brimonidine | Bimatoprost Ophthalmic Solution 0.01% and Vehicle | Brimonidine Tartrate Ophthalmic Solution 0.2% |
|---|---|---|---|
| STARTED | 38 | 36 | 38 |
| COMPLETED | 38 | 36 | 37 |
| NOT COMPLETED | 0 | 0 | 1 |
Reasons for not completing this period:
| Reason | Fixed-Combination Bimatoprost/Brimonidine | Bimatoprost Ophthalmic Solution 0.01% and Vehicle | Brimonidine Tartrate Ophthalmic Solution 0.2% |
|---|---|---|---|
| Adverse Event | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Modified Intent to Treat: all randomized and treated patients who had baseline and at least 1 postbaseline IOP assessment
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.
| Characteristic | Unit | Fixed-Combination Bimatoprost/Brimonidine | Bimatoprost Ophthalmic Solution 0.01% and Vehicle | Brimonidine Tartrate Ophthalmic Solution 0.2% | Total |
|---|---|---|---|---|---|
| Participants analysed | 38 | 36 | 38 | 112 | |
| Age, Customized: <45 years | Participants | 1 | 0 | 0 | 1 |
| Age, Customized: Between 45 and 65 years | Participants | 21 | 14 | 20 | 55 |
| Age, Customized: >65 years | Participants | 16 | 22 | 18 | 56 |
| Sex: Female, Male: Female | Participants | 20 | 22 | 25 | 67 |
| Sex: Female, Male: Male | Participants | 18 | 14 | 13 | 45 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Average Eye Mean Diurnal Intraocular Pressure (IOP), measured over Baseline, Day 42.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Millimeters of Mercury (mmHg) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline in average-eye mean diurnal intraocular pressure, measured at Baseline and Day 42, with pressure expressed in millimeters of mercury (mmHg). The registry defines average-eye mean diurnal IOP as the mean of the average IOPs from the right and left eyes at hours 0, 2, 4, 8 and 12. The resulting measure captures pressure across the specified measurement times rather than relying on a reading from a single time of day.
Change from baseline expresses the follow-up value relative to the starting value. Under the registry’s definition, a negative change indicates a reduction in IOP, while a positive change indicates an increase. This direction makes the sign of a reported estimate important: a negative value is not itself a between-treatment comparison, and an estimate for one group alone cannot establish how that group compares with another.
A continuous endpoint such as IOP can be summarized by a mean, with a standard deviation describing the spread of observed measurements around that mean. The registry identifies the endpoint parameter as a mean and the dispersion measure as a standard deviation, but it does not report the group means, standard deviations, changes, or treatment contrasts. The endpoint is therefore defined, but its results cannot be evaluated from the registry record.
IOP is used as the study’s measured outcome. The record’s endpoint description does not itself establish the clinical meaning of any unreported change, and no treatment conclusion follows from the endpoint definition alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a specific primary endpoint and the population in which it was intended to be assessed, but it does not report the primary outcome data. In particular, it gives no treatment-group changes from baseline, between-group estimate, standard error, confidence interval, or p-value for change in average-eye mean diurnal IOP. The result of the primary comparison is therefore not reported in the registry record. It is not possible to describe the size, direction, or precision of a treatment difference using the posted outcome information.
This absence matters because the endpoint’s direction is interpretable only when an actual estimate is available. A negative change would indicate a reduction from baseline within the group described; a positive change would indicate an increase. To assess a comparative effect, readers would need an estimate that contrasts the relevant randomized groups, along with information about its uncertainty and the analysis used. No such estimate or analysis is reported.
The listed secondary outcomes are change from baseline in average-eye mean diurnal IOP and average-eye mean diurnal IOP. Their numerical results are also not reported in the registry record. The registry lists three outcome measures and zero analyses. Those entries do not supply the underlying data or statistical comparisons needed to evaluate the primary or secondary outcomes.
For safety, the record lists serious-event and other-adverse-event counts for each treatment group. The serious-event counts are low in the sense that the entries include zero or one affected participants per group, while the other-adverse-event counts are larger. Those counts describe what is listed in the record; they do not establish whether event risks differ between regimens. The record also lists breast cancer and acute myocardial infarction among the top serious-event terms, with percentages, but does not provide enough context to interpret these entries as comparative treatment effects. Death results are not reported in the registry record.
Randomization and masking are design features, not outcome findings. They can support a fair comparison when properly implemented and when outcome data are analyzed appropriately, but the registry record does not report the detailed allocation process or analysis. Without reported outcome estimates and their uncertainty, the treatment groups cannot be ranked on the primary endpoint from this record. This is a limitation of the available registry results, rather than evidence that the groups were identical or that a difference was present.
9. Statistical Methods Explained
What does the primary measure summarize?
Average-eye mean diurnal IOP is a continuous measure. The record defines it by averaging right- and left-eye pressure and then using readings at hours 0, 2, 4, 8 and 12. Summarizing readings across the specified times can characterize pressure over the measurement period rather than emphasize a single reading. The primary endpoint then expresses the follow-up measure as change from baseline. The registry states that the analysis parameter is a mean and that standard deviation is the dispersion measure.
In general, a mean describes the central level of a continuous measurement, while a standard deviation describes how spread out individual measurements are around that mean. These quantities answer different questions: the mean concerns the average level, while the standard deviation concerns variability among observations. Neither is reported numerically for this trial’s primary endpoint, so they cannot be used to reconstruct or assess the result.
How should a treatment contrast be read?
In general, a within-group change and a between-group contrast are not interchangeable. A within-group change compares a group’s follow-up measurement with its baseline. A between-group contrast compares outcome summaries across randomized regimens and is the quantity that addresses whether observed outcomes differed between treatment assignments. A suitable contrast also needs an uncertainty estimate. A confidence interval communicates a range of estimates compatible with the data and analysis under its assumptions; its width conveys precision. The registry record does not report a confidence interval, a contrast, or a p-value for the primary outcome.
Because the outcome is continuous, analyses often use methods that model means or mean changes, but the exact model for this trial is not reported in the registry record. The record does not say whether the primary comparison used change scores, adjusted follow-up measurements for baseline, accounted for correlations between eyes, or handled repeated measurements in a particular way. These are methodological choices that can affect the estimand and its uncertainty, and should not be inferred from the endpoint description alone.
What do randomization and masking contribute?
In general, randomization aims to make treatment assignment independent of participant characteristics, reducing the risk that systematic baseline differences explain an observed contrast. Chance differences can remain, especially in a study with limited enrollment. Masking can reduce the influence of treatment knowledge on care, reporting, measurement, or assessment, depending on which people are masked. The registry identifies the study as randomized and double-masked but does not report the allocation method, concealment, masked roles, or masking procedures. These design labels do not substitute for reported outcome results.
What is the sample-size illustration?
The registry record describes sample-size assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect specified as a fraction of the observed effect. It explicitly distinguishes this illustration from the trial’s own design. Accordingly, any sample-size values associated with that calculation are planning illustrations, not observed power and not evidence that the study was designed around a particular effect. The registry does not report the trial’s sample-size justification or explain how the enrollment was selected.
The phrase “observed effect” in a planning calculation refers to an effect estimate used as an input to an illustrative calculation. Such a calculation does not establish that a future study would have a guaranteed probability of detecting an effect, and it does not resolve uncertainty in the original estimate. The record does not report numerical primary-effect results with which readers could independently assess the basis for that illustration.
Why does over-dispersion matter in general?
For outcomes with counts, over-dispersion means that variability exceeds what a basic count model would expect. Accounting for excess variability can improve uncertainty estimates when that feature is present. The primary endpoint in this record is a continuous pressure measure, and the registry does not report an over-dispersion analysis. This general concept should not be mistaken for a method used in this trial.
More broadly, statistical significance and clinical importance are distinct ideas. A p-value, when reported, describes how data compare with a specified statistical model under a null hypothesis; it is not a measure of effect size or the probability that a treatment is beneficial. A confidence interval can help assess both magnitude and precision. Neither a p-value nor a confidence interval for the primary outcome is reported in the registry record, so these concepts cannot be applied to a trial-specific estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome and two secondary outcome descriptions, along with three outcome measures. It does not report outcome analyses. The record therefore does not show how comparisons across outcomes, treatment groups, or measurement times were handled. A multiplicity plan, including any adjustment or hierarchy for statistical testing, is not reported in the registry record. Without that information, readers cannot determine whether any reported significance claims were protected against the increased chance of false-positive findings from multiple testing; no such claims are reported in any case.
The primary analysis population is defined as Modified Intent to Treat: all randomized and treated patients who had baseline and at least one postbaseline IOP assessment. This definition indicates that inclusion required a postbaseline assessment as well as baseline data. It does not establish how many participants met the definition, how many lacked measurements, or whether additional exclusions occurred. The number analyzed for the primary endpoint is not reported in the registry record.
The record does not describe missing-data methods, reasons for missing measurements, sensitivity analyses, or how incomplete follow-up was handled. In general, missing outcome data can affect estimates if the people with observed measurements differ systematically from those without them. The direction and extent of any such effect cannot be assessed without information about missingness and the analysis approach.
The registry record also does not report whether the analysis followed randomized assignment for all relevant participants, how protocol deviations were handled, or whether the analysis population differed from the stated endpoint population. These omissions limit evaluation of the estimand and of the potential influence of incomplete outcome data.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Fixed-Combination Bimatoprost/Brimonidine | 0 | 38 | 0.0% |
| Bimatoprost Ophthalmic Solution 0.01% and Vehicle | 1 | 36 | 2.8% |
| Brimonidine Tartrate Ophthalmic Solution 0.2% | 1 | 38 | 2.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Fixed-Combination Bimatoprost/Brimonidine | 27 of 38 |
| Bimatoprost Ophthalmic Solution 0.01% and Vehicle | 25 of 36 |
| Brimonidine Tartrate Ophthalmic Solution 0.2% | 20 of 38 |
Most frequent serious adverse event terms
| Event term | Organ system | Fixed-Combination Bimatoprost/Brimonidine | Bimatoprost Ophthalmic Solution 0.01% and Vehicle | Brimonidine Tartrate Ophthalmic Solution 0.2% |
|---|---|---|---|---|
| Breast Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 38 | 1 of 36 | 0 of 38 |
| Acute Myocardial Infarction | Cardiac disorders | 0 of 38 | 0 of 36 | 1 of 38 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Fixed-Combination Bimatoprost/Brimonidine | Bimatoprost Ophthalmic Solution 0.01% and Vehicle | Brimonidine Tartrate Ophthalmic Solution 0.2% |
|---|---|---|---|---|
| Conjunctival Hyperaemia | Eye disorders | 18 of 38 | 16 of 36 | 2 of 38 |
| Eye Pruritus | Eye disorders | 5 of 38 | 5 of 36 | 3 of 38 |
| Punctate Keratitis | Eye disorders | 2 of 38 | 4 of 36 | 2 of 38 |
| Eye Discharge | Eye disorders | 3 of 38 | 1 of 36 | 1 of 38 |
| Eye Pain | Eye disorders | 2 of 38 | 1 of 36 | 2 of 38 |
| Dry Mouth | Gastrointestinal disorders | 0 of 38 | 1 of 36 | 4 of 38 |
| Vision Blurred | Eye disorders | 1 of 38 | 1 of 36 | 2 of 38 |
| Eye Irritation | Eye disorders | 0 of 38 | 3 of 36 | 1 of 38 |
| Blepharospasm | Eye disorders | 3 of 38 | 0 of 36 | 0 of 38 |
| Instillation Site Pruritus | General disorders | 2 of 38 | 1 of 36 | 0 of 38 |
Serious events with the highest arm-level rate: breast cancer (2.8%), acute myocardial infarction (2.6%).
The registry reports serious adverse-event entries and other-adverse-event entries by treatment group. For fixed-combination bimatoprost/brimonidine, the serious-event fields list 0 affected among 38 at risk, and the other-adverse-event fields list 27 affected among 38 at risk. For bimatoprost ophthalmic solution 0.01% with vehicle, those entries are 1 among 36 for serious events and 25 among 36 for other adverse events. For brimonidine tartrate ophthalmic solution 0.2%, they are 1 among 38 for serious events and 20 among 38 for other adverse events.
These are registry counts, not comparative estimates. The record does not report statistical comparisons, confidence intervals, event timing, or exposure-adjusted rates. It also does not explain whether participants could contribute more than one event to the listed categories, so the counts should not be treated as a complete account of event frequency or severity.
The record lists breast cancer at 2.8% and acute myocardial infarction at 2.6% among the top serious-event terms. It does not provide enough accompanying detail to attribute these terms to a particular treatment group or interpret them as evidence of a treatment-related difference. Death results are not reported in the registry record. The observed counts alone do not establish comparative safety.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, double-masked Phase 2 study evaluated fixed-combination bimatoprost and brimonidine against regimens involving bimatoprost with vehicle and brimonidine alone. It defines a primary endpoint based on change in average-eye mean diurnal IOP at Baseline and Day 42, and it gives a Modified Intent to Treat population definition. Those details explain what the study intended to measure and how the primary population was described.
The record does not report the primary endpoint results or analyses. Consequently, it does not show the size or direction of a comparative effect, its precision, or whether an analysis found evidence of a difference. This absence cannot be interpreted as evidence that treatments were equivalent, that there was no effect, or that a particular regimen performed better. Those conclusions would require outcome estimates and appropriate uncertainty information.
The adverse-event entries are descriptive counts, not a basis for concluding that one regimen has greater or lesser risk. The registry does not supply the context needed for a complete safety comparison, such as event timing, severity distributions, statistical comparisons, or an explanation of how repeat events were counted. The listed serious-event terms and percentages also do not establish causation.
More generally, a registry record is a record of study characteristics and posted results, not a substitute for a complete report of methods and analyses. Randomization and masking are relevant design features, but their presence does not guarantee that all potential sources of bias were eliminated. Interpretation also depends on outcome completeness, the analysis population, model choices, and prespecified handling of multiple comparisons. Several of those details are not reported.
The appropriate statistical conclusion is limited: the trial design and endpoint are described, and some adverse-event counts are listed, but the primary efficacy result is not reported in the registry record. No medical recommendation or treatment conclusion can be drawn from those omissions or from the descriptive safety figures alone.
13. Why This Trial Matters Statistically
This trial illustrates why an endpoint definition and a trial result are different kinds of information. The registry specifies how average-eye mean diurnal IOP was constructed, when it was assessed, and how the sign of a change should be interpreted. That detail is useful for understanding what a reported estimate would mean. Yet, without the group estimates and a comparative analysis, readers cannot determine the direction, magnitude, or precision of the primary result.
The randomized, double-masked, parallel design provides a framework for comparing assigned regimens. In general, randomization can reduce systematic baseline confounding, and masking can limit some influences on measurement and reporting. But those design features are most informative when accompanied by transparent reporting of analysis methods, participant flow, missing data, and outcome estimates. The registry record does not report many of those details.
The study also highlights the importance of distinguishing safety counts from safety comparisons. Group-specific counts can describe events recorded in the registry, but they do not alone show whether the underlying risks differ. Event definitions, follow-up, exposure, completeness, and uncertainty all matter when interpreting safety data. The record’s lack of comparative analyses limits what can be learned from the counts.
For biostatisticians and clinical researchers, the record is a reminder that statistical interpretation depends on both study design and the completeness of reporting. A defined outcome, stated analysis population, and posted counts are not enough to reconstruct an unreported primary analysis. The most defensible reading separates what the registry documents from what remains unknown, without treating missing results as evidence for or against a treatment effect.
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 central limitation for interpreting this trial is that the primary endpoint results are not reported in the registry record. There are no group-specific changes, between-group estimates, confidence intervals, or p-values for the primary outcome. Without these quantities, the size and precision of any treatment contrast cannot be assessed.
The record identifies the primary endpoint population but does not report its size or the number of participants with usable measurements. It does not describe participant flow, protocol deviations, reasons for missing IOP assessments, missing-data methods, or sensitivity analyses. The effect of incomplete follow-up therefore cannot be evaluated.
Although the trial is identified as randomized and double-masked, operational details are not reported. The registry does not describe the randomization sequence, allocation concealment, masked roles, or procedures for maintaining masking. It also does not report the statistical model or the approach used to compare treatment groups, account for repeated measurements, or handle measurements from both eyes.
The record lists secondary outcomes and outcome-measure counts but does not provide analyses or a multiplicity plan. The sample-size assumptions are explicitly described as a planning illustration rather than the trial’s own design justification, and the registry does not report the original sample-size rationale. These gaps prevent evaluation of whether the study was planned and analyzed around a prespecified effect or testing strategy.
Safety interpretation is similarly limited. Counts are listed, but comparative analyses, event timing, and details on repeat events are not reported. Death results are not reported in the registry record. These limitations concern the available registry information; they do not by themselves indicate what the full study report might contain.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Safety and Efficacy Study of Fixed-Combination Bimatoprost and Brimonidine in Chronic Glaucoma or Ocular Hypertension — NCT01863953.
- Registry record last updated 2015-01-26; status last verified 2015-01.
- Results first posted 2015-01-26.
- 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.
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18. Record Summary
The registry record describes a completed, randomized, double-masked, parallel-group Phase 2 study sponsored by Allergan in chronic glaucoma or ocular hypertension. Enrollment is listed as 112, with start and primary-completion dates of 2013-06 and 2013-12. The study compared fixed-combination bimatoprost/brimonidine with bimatoprost plus vehicle and brimonidine regimens, each specified for 6 weeks.
The primary endpoint was change from baseline in average-eye mean diurnal IOP, measured at Baseline and Day 42. Its population was defined as randomized and treated patients with baseline and at least one postbaseline IOP assessment. The registry record does not report the primary outcome results or analyses. It lists adverse-event counts by group and two serious-event terms, but does not report comparative safety analyses or death results. The record’s sample-size assumptions are described as a planning illustration, not as the trial’s own design rationale.