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 Safety and Pharmacodynamics Study of AGN-207281 Ophthalmic Solutions Compared With Timolol Ophthalmic Solution or Placebo in Patients With Ocular Hypertension or Primary Open-Angle Glaucoma (NCT01215786), a randomized phase 1 study. The primary outcome is Change From Baseline in Worse Eye Intraocular Pressure (IOP) at Day 14.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01215786 |
| Phase | Phase 1 |
| Condition | Glaucoma, Open-Angle, Ocular Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 50 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Allergan |
| Results posted | Yes |
2. Clinical Question
Population
Patients with ocular hypertension or primary open-angle glaucoma. The primary endpoint population is described as the safety population: patients who started the study and received treatment. The registry record lists an enrollment of 50, but does not report how many participants contributed data to the primary endpoint.
Intervention
AGN-207281 ophthalmic solution, given as 0.1% on Days 1-7 and 0.3% on Days 8-14. The study summary describes evaluation of up to 3 doses based on an ongoing review of study data; the registry record does not explain how that review determined dosing.
Comparator
The listed comparison groups are timolol ophthalmic solution 0.5% and AGN-207281 vehicle ophthalmic solution, identified as placebo. The registry record does not provide a numerical primary-endpoint comparison between the AGN-207281 group and either comparator.
Primary question
How did mean worse-eye intraocular pressure change from baseline to Day 14 in the safety population? The endpoint description says that a negative change indicates lower pressure. No group means, estimated differences, confidence intervals, or primary-endpoint analyses are reported in the registry record.
This is an exploratory safety and pharmacodynamics study, rather than a record with a reported numerical estimate for the primary endpoint. The outcome is defined as a mean change in pressure, measured in millimeters of mercury (mm Hg), with the worse eye determined by the higher baseline pressure. Plasma concentration of AGN-207281 is also listed as a secondary outcome at Day 7 and Day 14. The registry record names those measurements but does not report their results. Therefore, the clinical question can be described from the endpoint definition and study arms, but the posted record does not establish the size or precision of any treatment-group difference.
3. Trial Design
The registry record identifies this as a randomized, triple-masked, parallel-group phase 1 study. It lists an enrollment of 50 and a completed status. The study began in 2010-10, and primary completion was recorded in 2010-12. The record does not explain who was masked, how the randomization sequence was generated or concealed, or how participants were allocated among the groups.
The listed groups received AGN-207281 ophthalmic solution, timolol ophthalmic solution 0.5%, or placebo. The AGN-207281 regimen is described as 0.1% on Days 1-7 followed by 0.3% on Days 8-14. The placebo is identified as AGN-207281 vehicle ophthalmic solution. The study summary describes evaluation of up to 3 doses based on an ongoing review of data during the study period, but the specific review process and its influence on treatment assignment or dosing are not reported in the registry record.
The primary endpoint was change from baseline in worse-eye intraocular pressure at Day 14. The endpoint was defined for the safety population, consisting of patients who started the study and received treatment. Plasma concentrations at Day 7 and Day 14 are listed as secondary outcomes. The registry record lists 3 outcome measures and 0 analyses. It does not report the statistical analysis plan, a sample-size justification, handling of missing endpoint measurements, or whether any interim analyses were planned.
Randomization can help balance measured and unmeasured characteristics across groups, while masking can reduce the influence of treatment knowledge on care and outcome assessment. These are general methodological benefits, not evidence that the procedures were implemented successfully in this particular study. The registry record does not provide enough detail to assess the randomization or masking procedures.
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: Patients in the AGN-207281 ophthalmic solution arm received AGN-207281 ophthalmic solution 0.1% on Days 1 to 7 and AGN-207281 ophthalmic solution 0.3% on Days 8 to 14.
Overall Study
| Stage | AGN-207281 Ophthalmic Solution | Timolol Ophthalmic Solution 0.5% | Placebo |
|---|---|---|---|
| STARTED | 21 | 19 | 10 |
| COMPLETED | 21 | 19 | 10 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety population, which consisted of all patients who started the study and received treatment.
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 | AGN-207281 Ophthalmic Solution | Timolol Ophthalmic Solution 0.5% | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 21 | 19 | 10 | 50 | |
| Age, Customized: <45 years | participants | 0 | 0 | 1 | 1 |
| Age, Customized: Between 45 and 65 years | participants | 7 | 7 | 2 | 16 |
| Age, Customized: >65 years | participants | 14 | 12 | 7 | 33 |
| Sex: Female, Male: Female | Participants | 13 | 8 | 7 | 28 |
| Sex: Female, Male: Male | Participants | 8 | 11 | 3 | 22 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Worse Eye Intraocular Pressure (IOP) at Day 14, measured over Baseline, Day 14.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Millimeters of mercury (mm Hg) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline in worse-eye intraocular pressure at Day 14, reported as a mean in millimeters of mercury (mm Hg). Intraocular pressure is a measurement of fluid pressure inside the eye. The worse eye is defined as the eye with the higher baseline pressure. A negative change indicates a reduction in pressure, according to the endpoint description.
Using change from baseline describes how the measurement at follow-up differs from a participant’s starting measurement. In general, this can account for some variation in starting pressure when comparing average changes between groups. The mean summarizes the group’s average change, while the standard deviation describes how spread out individual measurements are around that average. These are general interpretations of the stated summary measures.
The Day 14 endpoint reflects the measurement at the end of the listed AGN-207281 treatment sequence. Its definition does not itself show whether groups differed or how precisely any difference was estimated. The registry record does not report the group means, standard deviations, treatment contrasts, or confidence intervals for this endpoint. It also does not report the number of participants with evaluable baseline and Day 14 measurements. The listed safety population includes patients who started treatment, but the record does not say whether every member of that population had complete endpoint data.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a clinically relevant measurement and a direction of change: a negative change in worse-eye intraocular pressure indicates a reduction from baseline. It does not report the numerical primary-endpoint results. There are no posted group means, standard deviations, between-group estimates, confidence intervals, or p-values for the Day 14 endpoint. Consequently, the direction, magnitude, and precision of the primary outcome cannot be assessed from the registry record.
The outcome is continuous, and the stated summary is a mean with standard deviation. In general, the mean describes the average change in a group, while the standard deviation describes variability among individual measurements. A comparison between groups would ordinarily need an estimate of the difference in mean change, together with information about its uncertainty. Neither the estimate nor its uncertainty is reported in the registry record. A mean change within one group alone would also not establish how that group compared with timolol or placebo.
The record lists plasma concentration outcomes at Day 7 and Day 14, but does not report their numerical results. It also lists 0 analyses. The study summary calls the investigation exploratory and describes an ongoing review of data, but the registry record does not provide the results of that review or explain its statistical role. No numerical efficacy or pharmacodynamic conclusion can therefore be drawn from the listed outcome names alone.
For safety, the registry lists 0 participants with serious adverse events in each group. It also lists other adverse events affecting 9 of 21 participants in the AGN-207281 group, 19 of 19 in the timolol group, and 2 of 10 in the placebo group. These are descriptive counts in the record; they are not adjusted comparisons and do not describe event severity, timing, or causality. The registry record does not report death counts, and no serious adverse-event terms are listed.
Overall, the posted information supports a description of the trial design, endpoint definition, and recorded adverse-event counts. It does not support a numerical estimate of the primary treatment effect or a judgment about its precision. Absence of a reported outcome estimate is not evidence that there was no effect; it means the registry record does not report the information needed to assess one.
9. Statistical Methods Explained
What does the endpoint summary mean? The primary endpoint is a continuous measurement: change in worse-eye intraocular pressure from baseline to Day 14. The registry specifies the mean and standard deviation as the summary statistics. In general, a mean is the arithmetic average of observed values, and a standard deviation describes how dispersed those values are around the mean. These summaries convey different information: the mean describes the group’s average change, while the standard deviation describes participant-level variability.
The endpoint description defines negative change as a reduction in pressure. This direction rule helps interpret a reported value, but it does not supply a result. The group means and standard deviations are not reported in the registry record, nor is a between-group treatment contrast. Without those values, the amount of change and the difference between treatment groups cannot be assessed.
Why does a confidence interval matter? In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of the statistical method. Its width communicates precision: a narrower interval indicates greater precision than a wider interval, all else being equal. A confidence interval for a difference in mean change would help readers assess both the possible size and uncertainty of a group contrast. No confidence interval for the primary endpoint is reported in the registry record.
A p-value, when reported, addresses how compatible observed data are with a specified statistical null hypothesis under the method’s assumptions. It does not measure the size or clinical importance of an effect, and it does not replace an estimate with an interval. The registry record does not report a primary-endpoint p-value or the test used. It therefore does not permit an interpretation of statistical significance for that endpoint.
What does randomization contribute? In general, random assignment is intended to make treatment groups comparable at the start of a trial, including with respect to characteristics that are measured and those that are not. This supports interpretation of between-group differences, provided the trial procedures and analysis are appropriate. The record identifies the study as randomized, but the sequence-generation and allocation-concealment procedures are not reported in the registry record. The label alone does not allow those details to be evaluated.
The study is also described as triple-masked. Masking can reduce bias when participants, investigators, or outcome assessors do not know assigned treatment, depending on who is masked. The registry record does not specify which roles were masked or how masking was maintained. The study’s classification can be reported, but the practical protections against bias cannot be assessed from that label alone.
How should the planning assumptions be understood? The record’s planning assumptions describe illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They state that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a report of the study’s original design justification. The registry record does not provide the sample-size justification for the trial, and it does not report numerical planning estimates in the information available for this interpretation.
Such planning illustrations are conditional: they depend on the chosen effect, error-rate convention, allocation, and statistical approximation. They should not be described as observed power. Power calculations made after a study using an observed effect do not reveal how likely the study was to detect a prespecified effect before data collection. The record also does not report whether the stated assumptions match the study’s actual design or analysis.
Why can variability matter? The standard deviation is relevant because participant measurements may vary around the group mean. In general, more variability makes an average difference harder to estimate precisely for a given amount of information. If the data are more variable than a simple model assumes, standard errors and confidence intervals from that model may not represent uncertainty well. Over-dispersion is a general concern when observed variability exceeds what a chosen probability model expects; whether it applies to this continuous endpoint cannot be assessed from the registry record.
What is not available for evaluating the analysis? The record lists 0 analyses and gives no primary-endpoint estimates. It does not report the statistical model, covariate adjustments, assumptions checks, treatment contrast, missing-data method, or handling of participants without Day 14 measurements. It also does not describe a prespecified hierarchy for outcomes or comparisons. These omissions prevent reconstruction or appraisal of the primary analysis. General statistical concepts can explain what such methods would address, but they cannot substitute for the study-specific analysis details that are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists the Day 14 change in worse-eye intraocular pressure as the primary endpoint and plasma concentrations at Day 7 and Day 14 as secondary outcomes. It also lists 3 outcome measures and 0 analyses. The record does not describe how many treatment comparisons were planned for the primary endpoint, whether secondary outcomes were confirmatory or exploratory, or whether any adjustment for multiple comparisons was planned.
In general, testing several outcomes or contrasts can increase the chance of at least one apparently notable result when each is assessed separately. A prespecified multiplicity strategy can control that risk, for example by adjusting tests or defining an order for interpretation. The registry record does not report such a strategy. Since no numerical primary or secondary outcome analyses are reported, the impact of multiplicity on the posted results cannot be evaluated.
The primary population is described as the safety population, consisting of patients who started the study and received treatment. The record does not report a separate intention-to-treat or per-protocol population, nor does it explain how participants were assigned to analysis populations. It does not provide the number with available Day 14 measurements or say how missing measurements were handled. In general, missing-data methods can affect estimates when the availability of an outcome is related to treatment or participant characteristics; the registry record does not give enough information to assess that issue.
The study summary mentions an ongoing review of data during the study period. The registry record does not report whether formal interim analyses were conducted, whether decisions were made using statistical boundaries, or how any repeated looks at data were accounted for. Those details are not reported in the registry record, so the effect of data review on inference cannot be assessed.
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 |
|---|---|---|---|
| AGN-207281 Ophthalmic Solution | 0 | 21 | 0.0% |
| Timolol Ophthalmic Solution 0.5% | 0 | 19 | 0.0% |
| Placebo | 0 | 10 | 0.0% |
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 |
|---|---|
| AGN-207281 Ophthalmic Solution | 9 of 21 |
| Timolol Ophthalmic Solution 0.5% | 19 of 19 |
| Placebo | 2 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AGN-207281 Ophthalmic Solution | Timolol Ophthalmic Solution 0.5% | Placebo |
|---|---|---|---|---|
| Eye irritation | Eye disorders | 7 of 21 | 8 of 19 | 0 of 10 |
| Punctate keratitis | Eye disorders | 0 of 21 | 4 of 19 | 0 of 10 |
| Lacrimation increased | Eye disorders | 1 of 21 | 2 of 19 | 0 of 10 |
| Eye pain | Eye disorders | 1 of 21 | 1 of 19 | 0 of 10 |
| Eye discharge | Eye disorders | 0 of 21 | 1 of 19 | 0 of 10 |
| Vision blurred | Eye disorders | 0 of 21 | 1 of 19 | 0 of 10 |
| Joint sprain | Injury, poisoning and procedural complications | 0 of 21 | 1 of 19 | 0 of 10 |
| Headache | Nervous system disorders | 0 of 21 | 1 of 19 | 0 of 10 |
| Back pain | Musculoskeletal and connective tissue disorders | 0 of 21 | 0 of 19 | 1 of 10 |
| Foreign body sensation in eyes | Eye disorders | 0 of 21 | 0 of 19 | 1 of 10 |
The registry record reports 0 participants with serious adverse events in the AGN-207281 group, 0 in the timolol group, and 0 in the placebo group. For other adverse events, it reports 9 of 21 participants in the AGN-207281 group, 19 of 19 in the timolol group, and 2 of 10 in the placebo group. These are the counts recorded for the groups, not adjusted comparisons. The record does not provide event-level descriptions or explain how multiple events in a participant were handled.
Serious adverse events and other adverse events are presented separately in the registry record. A count of participants affected does not convey the number of episodes, their duration, severity, timing, or relationship to treatment. The record does not list serious adverse-event terms, and death counts are not reported in the registry record. A zero serious-event count means none are recorded in these group summaries; it does not establish that an event is impossible or rule out safety concerns that a study of this size or duration could not characterize.
The groups have different recorded denominators, so raw counts should be read alongside their listed group sizes rather than treated as direct measures of comparative risk. No statistical comparison of adverse events is reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the trial was designed to examine safety and pharmacodynamics of AGN-207281 ophthalmic solution in patients with ocular hypertension or primary open-angle glaucoma. It identifies timolol ophthalmic solution 0.5% and placebo as comparators, and defines a Day 14 primary endpoint based on change in worse-eye intraocular pressure. The record also supplies adverse-event counts and lists plasma concentration outcomes at Day 7 and Day 14.
It does not report the numerical primary-endpoint results. There is no reported estimate of mean change by group, no between-group difference, and no confidence interval describing precision. As a result, the available registry information does not show the direction or size of a primary-endpoint contrast. It also does not allow readers to determine whether a potential difference is estimated precisely or whether it could be compatible with a range of effects.
This absence should not be interpreted as a finding of no effect. It is a limit on what can be concluded from the record. The listed endpoint definition explains how a result would be interpreted, but it cannot replace the result itself. Likewise, the study’s randomized and triple-masked labels describe its design classification but do not supply evidence about the outcome or enough procedural detail to assess possible bias.
The study is identified as phase 1 and exploratory. That context helps describe its purpose, but it does not change the need for reported outcome estimates when interpreting treatment-group differences. The adverse-event counts are descriptive and do not establish comparative safety. Further information about event characteristics, statistical analyses, missing observations, and the primary endpoint would be needed for a fuller assessment. Nothing in the registry record alone supports medical advice or a treatment decision.
13. Why This Trial Matters Statistically
This study illustrates an important distinction between a clearly defined endpoint and a reported endpoint result. The registry record specifies a continuous measure, its timing, the population, and the direction in which change is interpreted. Those details define what the primary question concerns. However, the record lists 0 analyses and does not report group-level estimates or uncertainty. Without those results, readers cannot quantify the outcome or evaluate the precision of a treatment comparison.
The design labels also show why a registry description is only part of statistical interpretation. Randomization and masking are useful design features in general, but assessing their implementation requires details about sequence generation, concealment, and who remained unaware of assignment. Those details are not reported in the registry record. Similarly, an endpoint can be defined without revealing how missing measurements, multiple comparisons, or repeated data reviews were addressed in analysis.
The safety information demonstrates another distinction: counts of participants with events are not the same as a comparative analysis of risk. The record reports serious and other adverse-event counts, but does not give event descriptions, timing, or statistical comparisons. The listed denominators and counts are informative as descriptive records while remaining limited in what they establish.
For biostatisticians and clinical researchers, this trial is a reminder to separate study design, outcome definitions, analysis details, and numerical findings. Each contributes a different piece of evidence. When an estimate and its uncertainty are absent, the appropriate conclusion is that the registry record does not report them, rather than inferring a null result or reconstructing an analysis from the study description.
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 interpreting the primary outcome is that its numerical results are not reported in the registry record. Group means, standard deviations, treatment contrasts, confidence intervals, and p-values are absent. The record therefore does not permit assessment of the direction, magnitude, or precision of the Day 14 change in worse-eye intraocular pressure.
The record identifies a safety population but does not state how many participants had evaluable baseline and Day 14 measurements. Missing-data handling and the criteria used to define analysis populations are not reported in the registry record. Randomization and triple masking are listed, but sequence generation, allocation concealment, and the roles masked are not described. These omissions limit assessment of potential bias.
The summary describes ongoing review of data and evaluation of up to 3 doses, but the review procedures and their effect on dosing or analysis are not reported in the registry record. The statistical analysis plan, sample-size justification, interim-analysis procedures, multiplicity approach, and model assumptions are also not reported. Planning assumptions based on an observed effect do not establish the original design rationale.
The available safety results are counts of participants with serious or other adverse events. Event descriptions, timing, severity, causality assessments, and death counts are not reported in the registry record. The listed counts do not provide adjusted comparisons. The study’s enrollment of 50 and its phase 1, exploratory classification should also be considered when interpreting what the record can establish, without treating either as a substitute for the missing estimates or analysis details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Pharmacodynamics Study of AGN-207281 Ophthalmic Solutions Compared With Timolol Ophthalmic Solution or Placebo in Patients With Ocular Hypertension or Primary Open-Angle Glaucoma — NCT01215786.
- Registry record last updated 2015-08-17; status last verified 2015-07.
- Results first posted 2012-01-16.
- 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
NCT01215786 is a completed, randomized, triple-masked, parallel phase 1 study sponsored by Allergan. It lists an enrollment of 50, a start date of 2010-10, and primary completion in 2010-12. Participants had ocular hypertension or primary open-angle glaucoma and were assigned to AGN-207281 ophthalmic solution, timolol ophthalmic solution 0.5%, or placebo.
The primary endpoint was mean change from baseline in worse-eye intraocular pressure at Day 14, in mm Hg. Negative change was defined as a reduction. Plasma concentrations at Day 7 and Day 14 were listed as secondary outcomes. The registry record lists 3 outcome measures and 0 analyses, and does not report numerical results for the primary endpoint or plasma concentration outcomes.
The record reports 0 participants with serious adverse events in each group and lists other adverse events affecting 9 of 21, 19 of 19, and 2 of 10 participants across the AGN-207281, timolol, and placebo groups, respectively. Death counts and serious adverse-event terms are not reported in the registry record.