Safety and Efficacy of AGN-210961 Ophthalmic Solution Compared With Bimatoprost Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of AGN-210961 Ophthalmic Solution Compared With Bimatoprost Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension (NCT01110499), a randomized phase 2 study. The primary outcome is Part 1: Change From Baseline in Intraocular Pressure (IOP).

2. Clinical Question

The study addresses safety and IOP effects across different AGN-210961 formulations, with bimatoprost as the comparator. Its two parts use different treatment arrangements and durations, so their comparisons should not be treated as interchangeable. Part 1 compares treatments between a participant’s eyes; Part 2 assigns treatment to both eyes within a treatment group. The record identifies a selected formulation for Part 2 and lists that intervention as Formulation 7, but the selection process is not reported in the registry record.

3. Trial Design

This completed phase 2 study was randomized, triple-masked, and parallel-group, with enrollment of 163. It enrolled patients with ocular hypertension or primary open-angle glaucoma. The registry reports a start date of 2010-06 and primary completion in 2011-05.

The design had two parts. In Part 1, six groups received a different AGN-210961 formulation in one eye and bimatoprost ophthalmic solution 0.03% in the fellow eye once daily for 7 consecutive days. The registry describes the bimatoprost-treated eye data as combined across those groups. This fellow-eye arrangement means the treatment observations within a participant are linked rather than independent. It can support a within-participant comparison, but the registry record does not report the statistical model or comparison results.

In Part 2, the registry describes a formulation selected from Part 1 and compares treatment of both eyes with AGN-210961 against treatment of both eyes with bimatoprost, once daily for 4 weeks. The listed Part 2 interventions are AGN-210961 Formulation 7 and bimatoprost ophthalmic solution 0.03%. The number assigned to each group is listed as 39 and 40, respectively, in the adverse-event information; these figures are not a substitute for a reported primary-endpoint analysis population.

Randomization and triple masking are recorded, but the allocation procedure, masking roles, and concealment details are not reported in the registry record. The record does not describe the rationale for the enrollment target or explain how the two parts informed one another beyond the stated selection of a formulation.

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 was a 2-part study. Patients were enrolled in and completed Part 1 of the study. Then, based on a review of the data from Part 1, a different formulation was selected for Part 2 (Formulation 7). New patients were then enrolled in Part 2 of the study. No patients from Part 1 were enrolled in Part 2 of the study.

Only the first 6 of 8 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety Population: all treated patients

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.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Change From Baseline in Intraocular Pressure (IOP), measured over Baseline, Day 7.

The primary endpoint is change from baseline in intraocular pressure (IOP), expressed in millimeters of mercury and summarized as a mean with standard deviation. IOP measures fluid pressure inside the eye. The registry lists a baseline and Day 7 timeframe and specifies measurements at Hours 0, 2, 4, 6, 8, and 12. A negative change from baseline is described as a reduction in IOP.

Change scores express how a measurement differs from a participant’s own baseline. They can make the direction of change easy to interpret, while the mean describes the average change in a group. The standard deviation describes how varied individual measurements are around that group mean; it is not the uncertainty interval for the mean.

IOP is relevant to this study because the registry identifies it as an outcome of the eye-pressure effects of the study treatments. The listed time points also make the endpoint a set of measurements across the day, rather than a single observation. The registry record does not give the numerical means, standard deviations, or treatment comparisons for these time points. It also does not specify which measurement or combination of measurements was the primary basis for a single treatment conclusion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation. A continuous outcome such as IOP can be described by a mean and standard deviation. The mean indicates the group’s average measurement or average change. The standard deviation describes the spread of individual values around that mean. A confidence interval, when reported, describes uncertainty about an estimated quantity; it is not the same as the range containing most individual participants’ measurements. The registry identifies mean and standard deviation as the endpoint summary, but numerical summaries and confidence intervals are not reported in the registry record.

Change from baseline. A change score is calculated for each participant by comparing a follow-up measurement with baseline. The sign convention matters: in this study, negative change is described as a decrease in IOP. Comparing average change between treatment groups would address whether the groups changed differently, but the registry record does not report the treatment-effect estimate or the statistical test used. It also does not describe adjustment for baseline IOP.

Why does the fellow-eye arrangement matter?

General statistical explanation. When each participant receives one treatment in one eye and a comparator in the other, the two eye measurements share the participant’s characteristics. They are paired observations, not observations from unrelated people. A paired analysis uses each participant’s within-person treatment contrast and its variation. This can account for the relationship between a person’s two eyes. In Part 1, the registry describes this arrangement for each of six AGN-210961 formulations against bimatoprost in the fellow eye. The registry record does not report whether the primary analysis used paired differences or another method.

In Part 2, both eyes receive the treatment assigned to the participant’s group. This is not the same within-participant treatment contrast as Part 1. If eye-level measurements were analyzed, the two eyes would still be clustered within a participant. The analysis unit and handling of any correlation between eyes are not reported in the registry record.

How should repeated measurements be understood?

General statistical explanation. Measurements taken from the same eye over time are also related. Treating each time point as an independent observation can understate uncertainty because repeated observations from one eye share information. A repeated-measures method can model the pattern across time while accounting for within-eye correlation. The choice of model can affect estimates and uncertainty, especially when data are incomplete or the pattern of measurements differs over time.

The registry lists IOP measurements at Hours 0, 2, 4, 6, 8, and 12, with a baseline-to-Day 7 timeframe. It does not describe whether the time points were analyzed separately, jointly, or summarized into a single measure. The primary outcome has several categories or time points and is not reduced to one comparison in the posted results. A precise interpretation therefore requires details not reported in the registry record.

Why might multiplicity matter?

General statistical explanation. Testing many formulations, time points, or contrasts increases the chance that at least one comparison appears unusual by chance. An analysis plan may designate a primary contrast, adjust for multiple testing, or distinguish exploratory from confirmatory comparisons. The registry describes six formulations in Part 1 and multiple IOP measurement times, but does not report a multiplicity strategy or identify a single contrast as the basis for a definitive conclusion.

Randomization helps make treatment groups comparable in expectation, while masking can reduce some forms of bias in treatment administration or assessment. The registry records randomization and triple masking. It does not give the allocation method, which people were masked, or procedures used to preserve masking. Those design labels do not reveal how the endpoint was analyzed.

The record’s sample-size material is described as a planning illustration computed from an observed effect. It assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations are illustrations of participant counts under stated assumptions, not observed power and not evidence that the trial was designed around those assumptions. The registry does not report its own sample-size justification. No numerical planning estimates are stated in the record details summarized for this analysis.

Finally, analysis populations and missing data handling affect interpretation. The primary endpoint population is described as all treated patients, but the registry does not provide the number included in each endpoint analysis, missing-data counts, imputation rules, or sensitivity analyses. Without those details, it is not possible to assess whether the endpoint summaries include all treated participants or how incomplete measurements were handled.

10. Multiplicity, Missing Data and Analysis Populations

Part 1 evaluates six AGN-210961 formulations, and the IOP endpoint includes measurements at Hours 0, 2, 4, 6, 8, and 12. This creates multiple possible treatment and time-point comparisons. A prespecified primary comparison or a multiplicity adjustment can help control how multiple statistical tests are interpreted. The registry record does not report a multiplicity procedure, a hierarchy of comparisons, or which time point was designated as the principal contrast. The posted results do not reduce the primary endpoint’s several categories or time points to one comparison.

The registry calls the primary endpoint population the Safety Population: all treated patients. It does not report endpoint-specific analysis counts, the number of participants with missing measurements, reasons for missingness, or methods for handling missing IOP data. Rules for excluding observations or participants are also not reported in the registry record. As a result, the relationship between enrollment, treatment, and the analyzed IOP observations cannot be assessed from the posted information.

Randomization, triple masking, and a parallel-group model are recorded. The statistical analysis plan, interim analyses, model specification, and any adjustment for baseline values are not reported in the registry record. It is also not reported whether the Part 1 fellow-eye pairing or repeated measurements within an eye were accounted for analytically. These details matter because they determine the uncertainty attached to estimates and the interpretation of comparisons.

The sample-size material is a planning illustration based on an observed effect, not the trial’s reported design justification. The registry does not report its own sample-size rationale or a prespecified target difference. The stated illustration assumptions should not be interpreted as evidence of 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: dyspnoea (2.6%), lip and/or oral cavity cancer (2.5%).

The registry lists serious and other adverse events separately for each treatment group. In Part 1, each AGN-210961 formulation group lists 14 at risk for serious events and 0 affected. The combined Part 1 bimatoprost-treated-eye group lists 84 at risk and 0 affected. In Part 2, AGN-210961 Formulation 7 lists 39 at risk and 1 affected by a serious adverse event; the bimatoprost group lists 40 at risk and 1 affected.

For other adverse events, the listed affected counts are 10, 9, 10, 6, 7, and 5 across Part 1 Formulations 1 through 6, with 53 in the combined Part 1 bimatoprost-treated-eye group. Part 2 lists 29 affected with AGN-210961 Formulation 7 and 19 with bimatoprost. These are registry counts within the listed groups, not a formal comparison adjusted for study design or follow-up.

The registry lists Dyspnoea at 2.6% and Lip and/or Oral Cavity Cancer at 2.5% among top serious terms. The context and denominators for these terms are not reported in the registry record. Deaths are not reported in the registry record. Event counts alone do not establish whether treatments differ in safety, particularly across study parts with different treatment arrangements.

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

The record establishes that a randomized, triple-masked phase 2 study evaluated AGN-210961 formulations and bimatoprost in patients with ocular hypertension or primary open-angle glaucoma. It identifies change from baseline in IOP as the primary outcome and describes the measurement schedule. It also reports adverse-event counts for the listed groups.

However, numerical IOP results and the statistical treatment comparisons are not reported in the registry record. It is therefore not possible to describe how much IOP changed, whether changes differed between treatments, or how precisely any difference was estimated. The absence of an analysis result in the registry is not evidence that there was no change or no difference; it means the posted record does not answer those questions.

The study’s design also limits what can be inferred from a simple reading across its groups. Part 1 uses within-participant fellow-eye comparisons and combines bimatoprost eye data across formulation groups. Part 2 uses separate groups, each treated in both eyes, over a different duration. Results from these parts would need to be interpreted in light of their distinct comparisons and analysis methods. Those methods are not reported.

Adverse-event counts describe events recorded in the listed groups but do not by themselves provide a controlled estimate of relative risk or establish a treatment’s overall safety profile. The serious-event counts are low in the posted groups, but the record does not provide enough context to draw a comparative conclusion from them. The appropriate statistical reading is limited to the outcomes and counts actually reported, while recognizing that the primary efficacy result and its uncertainty are not available in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically instructive because its two parts use different comparison structures. Part 1 assigns different treatments to the two eyes of the same participant, creating paired observations. Part 2 assigns treatment by group and treats both eyes alike. Recognizing that distinction is important: the statistical analysis should reflect how treatment was assigned and how observations are related.

The IOP endpoint is also measured repeatedly across a set of times. Repeated observations can characterize a time profile, but a reader needs to know whether the analysis uses individual time points, an overall summary, or a model for the repeated measurements. Here, the registry lists several time points but does not report a single primary comparison or its analysis. This illustrates why an endpoint label alone is not enough to judge a study’s statistical evidence.

Part 1’s six formulations and multiple measurement times raise a multiplicity question. If many comparisons are examined, the reported statistical evidence depends on which contrasts were prespecified and how multiple testing was handled. Neither a multiplicity strategy nor endpoint analysis results are reported in the registry record.

The record also illustrates the difference between planning calculations and observed evidence. The sample-size material is described as an illustration based on an observed effect and stated assumptions. It is not a report of the original design justification and should not be treated as observed power. For readers, the key lesson is that design labels and planning assumptions cannot replace endpoint estimates, uncertainty intervals, and a clear account of the analysis.

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 main limitation for statistical interpretation is that numerical primary IOP results are not reported in the registry record. Means, standard deviations, treatment contrasts, and uncertainty intervals are not available in the study information, so the magnitude, direction, and precision of the primary outcome cannot be assessed.

The endpoint includes several measurement times, but the registry does not specify how they were combined or which comparison was primary. The record also does not describe an analysis method for the paired fellow-eye data in Part 1, repeated measurements within eyes, or the Part 2 group comparison. Multiplicity handling is not reported. These omissions prevent assessment of whether the analysis appropriately reflected the design.

Although the primary endpoint population is identified as all treated patients, the registry does not report the endpoint analysis population counts or missing-data handling. It is not possible to determine from the record whether all treated participants had usable measurements at each time point or how incomplete observations were addressed.

The two parts differ in duration and treatment assignment, and Part 1’s bimatoprost-treated-eye data are combined across groups. The record does not explain the detailed selection process for the Part 2 formulation or report a statistical link between parts. Safety counts are available, but event definitions and context for the listed serious-event terms are limited; deaths are not reported in the registry record. These constraints mean the posted information supports a description of the design and event counts, but not a firm comparative conclusion about IOP or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of AGN-210961 Ophthalmic Solution Compared With Bimatoprost Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension — NCT01110499.
• Registry record last updated 2014-08-05; status last verified 2014-07.
• Results first posted 2014-08-05.
• 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

NCT01110499 is a completed randomized, triple-masked, parallel-group phase 2 study sponsored by Allergan, with enrollment of 163. The registry lists patients with ocular hypertension or primary open-angle glaucoma and reports a start date of 2010-06 and primary completion in 2011-05.

Part 1 compared six AGN-210961 formulations, each given to one eye, with bimatoprost ophthalmic solution 0.03% in the fellow eye for 7 consecutive days. Part 2 compared AGN-210961 Formulation 7 with bimatoprost in both eyes once daily for 4 weeks. The primary outcome is change from baseline in IOP, recorded at multiple times and summarized as a mean with standard deviation.

The registry posts adverse-event counts but does not report numerical primary IOP results or analyses. Details on multiplicity, missing data, and the statistical analysis plan are not reported in the registry record.