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 Pharmacokinetics of the Brimonidine Tartrate Posterior Segment Delivery System in Patients Undergoing Pars Plana Vitrectomy (NCT01229410), a randomized phase 1 study. The primary outcome is Highest Vitreous Humor Level of Brimonidine in the Study Eye.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01229410 |
| Phase | Phase 1 |
| Condition | Vitrectomy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 24 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Allergan |
| Results posted | Yes |
2. Clinical Question
Population
Patients undergoing pars plana vitrectomy, with the primary endpoint population described as participants with pharmacokinetic data available in the per-protocol population. The registry record lists 24 participants enrolled overall; the primary endpoint lists 11 in the 400 µg arm and 12 in the 200 µg arm.
Intervention
A single intravitreal administration of a 400 µg brimonidine tartrate implant in the study eye on Day 1. The registry description says administration occurred 2, 4 or 8 weeks before pars plana vitrectomy.
Comparator
A single intravitreal administration of a 200 µg brimonidine tartrate implant in the study eye on Day 1, also described as occurring 2, 4 or 8 weeks before surgery. The study is listed as randomized, double masked and parallel, but details of allocation and masking are not reported in the registry record.
Primary question
What was the highest vitreous humor brimonidine level measured in the study eye for each treatment arm by the 60-day timeframe? The registry reports an arm-level maximum, not an average or an estimate of the typical participant's level. It does not report a statistical comparison between the dose arms.
The study concerns pharmacokinetics: how a drug is present in the body after administration. Its primary measure is the highest vitreous humor level of brimonidine in the study eye. Vitreous humor is described in the registry as the clear gel between the eye's lens and retina. The registry also lists the highest aqueous humor level and the percentage of patient samples with plasma brimonidine levels below the limit of quantitation as secondary outcomes.
The question is therefore descriptive and dose-focused. The posted primary values identify the largest recorded vitreous concentration in each arm during the stated timeframe. They do not by themselves describe the full concentration profile, the timing of each participant's maximum, or how concentrations varied between participants. Those details, as well as an inferential comparison of the arms, are not reported in the registry record.
3. Trial Design
This is a phase 1, randomized, double-masked, parallel study of brimonidine tartrate implants in patients undergoing pars plana vitrectomy. The registry lists an enrollment of 24 and the status as completed. The recorded study start is 2010-12, and primary completion is recorded as 2011-05. Allergan is listed as the sponsor.
The two intervention arms differ by implant dose: 400 µg and 200 µg of brimonidine tartrate. Both descriptions specify administration to the study eye on Day 1, with vitrectomy planned 2, 4 or 8 weeks later. The record does not explain how the timing categories were assigned, whether they were balanced across dose arms, or whether timing was included in the analysis. It also does not describe the randomization procedure, allocation concealment, or which people were masked.
A parallel design means participants are assigned to a treatment group rather than crossing between the treatment groups, as a general design concept. Randomization can support a fair comparison when treatment assignment is implemented as planned, while masking can reduce the influence of treatment knowledge on care or assessment. The registry labels this study randomized and double masked, but does not give further operational details about either feature.
The primary outcome is the highest vitreous humor brimonidine level in the study eye, with a 60-day timeframe. Its population is described as per protocol: all participants with pharmacokinetic data available. The endpoint data list 11 participants for the 400 µg implant and 12 for the 200 µg implant. The registry's overall enrollment and the endpoint analysis counts are different record entries; reasons for the difference are not reported in the registry record.
This design and endpoint describe a pharmacokinetic study, not a trial with a reported clinical efficacy comparison. The record lists three outcome measures and two secondary outcomes. It lists no analyses for the primary outcome, and no statistical comparison is posted. The protocol details, sample-size justification, interim analyses and statistical analysis plan are not reported in the registry record.
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 were enrolled in groups by planned time of pars plana vitrectomy (Week 2, 4, or 8 post-implant). Patients who had the implant removed during the vitrectomy did not complete the 6 month follow-up per protocol.
Overall Study
| Stage | 400 µg Brimonidine Tartrate Implant | 200 µg Brimonidine Tartrate Implant |
|---|---|---|
| STARTED | 12 | 12 |
| COMPLETED | 7 | 9 |
| NOT COMPLETED | 5 | 3 |
Analysis population for the primary outcome, as defined in the registry: Per Protocol: all subjects with pharmacokinetic data available
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 | 400 µg Brimonidine Tartrate Implant | 200 µg Brimonidine Tartrate Implant | Total |
|---|---|---|---|---|
| Participants analysed | 12 | 12 | 24 | |
| Age Continuous | Years | 69.7 (full range 2.87) | 66.5 (full range 9.67) | 68.1 (53 to 78) |
| Sex: Female, Male: Female | Participants | 8 | 6 | 14 |
| Sex: Female, Male: Male | Participants | 4 | 6 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Highest Vitreous Humor Level of Brimonidine in the Study Eye, measured over 60 Days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Nanogram/milliliter (ng/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the highest level of brimonidine measured in vitreous humor from the study eye in any participant in each treatment arm. The registry gives the unit as nanograms per milliliter and specifies a 60-day timeframe. Vitreous humor is the clear gel filling the space between the lens and retina.
Concentration measurements help characterize pharmacokinetics by describing the amount of a drug measured in a biological compartment. Reporting a maximum can be useful for describing the largest recorded concentration within an arm. It can also help distinguish the question being answered from one about average exposure, concentration at a prespecified visit, or the proportion of participants above a threshold. Those are different summaries and cannot be inferred from an arm maximum.
The posted values are 137.0 ng/mL for the 400 µg implant arm and 34.9 ng/mL for the 200 µg implant arm. These are maxima, not group means. They do not reveal how many participants had measurements near the maximum, the distribution of measurements, or whether a single participant contributed the maximum. The registry does not report individual-level data, measures of spread, or confidence intervals for this endpoint.
The endpoint is appropriate to describe the highest observed vitreous concentration within each arm, but it offers limited information about typical exposure or uncertainty. No inferential test or adjusted estimate for a between-arm contrast is reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint values are 137.0 ng/mL in the 400 µg implant arm and 34.9 ng/mL in the 200 µg implant arm. Each value is the highest vitreous humor brimonidine level reported for its arm, according to the registry description. The values therefore describe the upper observed measurement in each group, rather than the average level or a participant-level treatment effect.
The record lists 11 participants for the 400 µg endpoint and 12 for the 200 µg endpoint. The endpoint population is described as per protocol, consisting of participants with pharmacokinetic data available. The registry does not state why all enrolled participants are not represented in those endpoint counts, nor does it report how missing pharmacokinetic data were handled.
The numerical maxima should not be read as a complete comparison of drug exposure. A maximum depends on the range of observations and may be influenced by an unusually high measurement. Without a distribution, a measure of spread, individual observations or an interval estimate, the precision and representativeness of each arm maximum cannot be assessed from the posted endpoint results. The record also does not report a statistical test or model for comparing the doses.
The trial has a randomized, double-masked, parallel design in the registry record, but the reported endpoint summary remains descriptive. Randomization is relevant to a planned comparison; it does not turn separate maxima into an estimate of the difference in typical concentration. Likewise, masking does not supply information about uncertainty or analysis choices that are absent from the posted results.
The registry lists the highest aqueous humor level and the percentage of patient samples with plasma levels below the limit of quantitation as secondary outcomes. Their results are not included in the record details, so conclusions about those measurements cannot be drawn from the primary values. No results are posted for other pharmacokinetic characteristics, such as concentration over time, or for a clinically defined benefit.
In statistical terms, the primary result answers a narrow descriptive question: what was the largest recorded vitreous concentration in each arm by the stated timeframe? It does not establish how concentrations generally differed between arms, how precise a dose contrast would be, or what the results imply about clinical outcomes. The registry record does not report evidence for such broader conclusions.
9. Statistical Methods Explained
The primary outcome is a concentration summary, but its reported parameter is a number: the highest vitreous humor brimonidine level in any participant within each arm. This distinction matters. An arm maximum is not the same as a mean, median, or model-based estimate of a typical participant's concentration. It describes the extreme observation in the data summarized for that arm.
What does an arm maximum show?
A maximum identifies the largest observed value in a set of measurements. As a general statistical concept, it is sensitive to the number and pattern of observations, measurement variability and extreme values. It may be useful when the scientific question specifically concerns the largest recorded level, but it does not describe the distribution of all measurements. Two arms could have the same maximum while having very different typical values, or have different maxima despite substantial overlap in their underlying distributions.
For this endpoint, the registry reports 137.0 ng/mL for the 400 µg arm and 34.9 ng/mL for the 200 µg arm. The available summary does not show the lower and upper ranges of all observations, a central tendency, a standard deviation, or a confidence interval. No uncertainty interval can therefore be interpreted from the primary endpoint entry. It is also not possible to determine whether a maximum reflects one unusual observation or a broader pattern in the arm.
What would a confidence interval mean?
In general, a confidence interval expresses uncertainty around an estimate under a specified statistical procedure and its assumptions. For a comparison, an interval could communicate the range of effects compatible with the data and method. The registry record does not report an interval for the arm maxima or for a between-arm effect. That absence is important: the posted values alone do not quantify the precision of a dose comparison.
An interval for a group mean or for a difference in means would answer a different question from an interval for a maximum. The appropriate summary depends on the estimand, which is the precise quantity the analysis is intended to estimate. The registry description identifies the arm-specific maximum as the primary measure, but does not report an inferential estimand or comparison method.
Why not treat the values as a treatment effect?
A treatment effect is generally expressed as a comparison defined at the participant or group level, using a specified outcome and analysis. The two posted maxima are separate summaries. Subtracting them or otherwise transforming them would not supply the missing distributional information, uncertainty estimate or prespecified comparison. No such recalculated comparison is included in the registry record, and no sponsor comparison is reported. The values should therefore be read as descriptive arm results.
Randomization is a design feature intended to make treatment groups comparable on average, subject to implementation and chance. It does not eliminate the need to specify an analysis, report the data used, and quantify uncertainty. The record labels the study randomized, double masked and parallel, but details of the randomization method, masking procedures and analysis plan are not reported in the registry record.
What do the planning assumptions mean?
General sample-size planning uses assumptions about the effect to detect, the significance level, allocation, and statistical method. The record's planning description specifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as stated fractions of the observed effect. These are planning illustrations based on an observed effect, not the trial's own design justification. Any resulting sample-size illustration concerns a hypothetical future study under those assumptions; it is not a statement about the precision or power observed in this completed trial.
Observed power is not a substitute for an uncertainty interval. In general, calculations that use an observed effect after a study has concluded largely restate the observed result under chosen assumptions and do not provide an independent measure of evidence. The record does not report a sample-size justification, the effect targeted when the study was designed, or a prospective power calculation. The trial's planned sample size and rationale are not reported in the registry record.
How should the outcome structure be understood?
The primary endpoint is one of three listed outcome measures, and the record names two secondary outcomes. Multiple outcomes can raise multiplicity concerns when several hypotheses are tested, because repeated testing can increase the chance of at least one misleading positive finding. This is a general consideration, not a claim that such testing occurred in this study. The record lists no primary analyses and does not describe testing procedures, hierarchy, adjustment, or a multiplicity strategy.
Over-dispersion is a general issue for count data when variability exceeds what a simple model assumes. It does not appear to be the central issue for the reported primary endpoint, which is a continuous concentration summarized as an arm maximum. The registry does not report a model for the concentration outcome. No model assumptions should be inferred from the reported values alone.
The posted endpoint counts and values permit a direct descriptive reading but not a reconstruction of the underlying analysis. Individual-level measurements, measurement schedules, handling of values below quantitation limits for the primary endpoint, and data exclusions are not reported in the registry record. Without those details, readers cannot assess how the maximum was selected from available observations or whether the same measurement opportunities applied across participants and arms.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary outcome and two secondary outcomes: highest aqueous humor brimonidine level in the study eye, and the percentage of patient samples with plasma brimonidine levels below the limit of quantitation. Although three outcome measures are listed, results for the secondary outcomes are not reported in the registry record. The primary endpoint entry contains descriptive values, but the registry lists no analyses.
Multiplicity is a general statistical concern when several outcomes or hypotheses are tested. Without a stated analysis plan, testing hierarchy or adjustment method, it is not possible to determine whether or how multiplicity was addressed. The record does not report a prespecified primary hypothesis test or an inferential comparison between dose arms.
The primary outcome population is per protocol, described as all participants with pharmacokinetic data available. The endpoint data list 11 participants for the 400 µg arm and 12 for the 200 µg arm, while overall enrollment is recorded as 24. Reasons for the difference between these record entries, participant flow, exclusions, and missing-data handling are not reported in the registry record.
The endpoint description does not state how measurements missing at particular times were handled or how an individual participant's highest value was determined when data were incomplete. The record also does not report imputation, sensitivity analyses, or a comparison of the per-protocol population with any other analysis population. These omissions limit assessment of potential bias due to unavailable pharmacokinetic 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 |
|---|---|---|---|
| 400 µg Brimonidine Tartrate Implant | 1 | 12 | 8.3% |
| 200 µg Brimonidine Tartrate Implant | 2 | 12 | 16.7% |
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 |
|---|---|
| 400 µg Brimonidine Tartrate Implant | 11 of 12 |
| 200 µg Brimonidine Tartrate Implant | 12 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | 400 µg Brimonidine Tartrate Implant | 200 µg Brimonidine Tartrate Implant |
|---|---|---|---|
| Choroidal Detachment | Eye disorders | 1 of 12 | 0 of 12 |
| Atrial Fibrillation | Cardiac disorders | 1 of 12 | 0 of 12 |
| Vitreous Haemorrhage | Eye disorders | 0 of 12 | 1 of 12 |
| Retinal Detachment | Eye disorders | 0 of 12 | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 400 µg Brimonidine Tartrate Implant | 200 µg Brimonidine Tartrate Implant |
|---|---|---|---|
| Conjunctival Haemorrhage | Eye disorders | 7 of 12 | 6 of 12 |
| Conjunctival Hyperaemia | Eye disorders | 5 of 12 | 7 of 12 |
| Conjunctival Oedema | Eye disorders | 2 of 12 | 2 of 12 |
| Intraocular Pressure Increased | Investigations | 1 of 12 | 3 of 12 |
| Hypertension | Vascular disorders | 2 of 12 | 0 of 12 |
| Nasopharyngitis | Infections and infestations | 1 of 12 | 1 of 12 |
| Cataract | Eye disorders | 1 of 12 | 1 of 12 |
| Eye Pain | Eye disorders | 1 of 12 | 1 of 12 |
| Vitreous Haemorrhage | Eye disorders | 0 of 12 | 2 of 12 |
| Retinal Detachment | Eye disorders | 0 of 12 | 2 of 12 |
Serious events with the highest arm-level rate: choroidal detachment (8.3%), atrial fibrillation (8.3%), vitreous haemorrhage (8.3%), retinal detachment (8.3%).
The registry lists serious adverse events for each dose arm. In the 400 µg implant arm, 1 participant is listed as having a serious adverse event, with 12 at risk. In the 200 µg implant arm, 2 participants are listed as having a serious adverse event, also with 12 at risk. These are descriptive counts, not a reported statistical comparison between arms.
The record lists Choroidal Detachment, Atrial Fibrillation, Vitreous Haemorrhage and Retinal Detachment among the top serious terms, each with a reported 8.3%. The information does not specify in the registry record which arm is associated with each term, whether terms could occur in the same participant, or how the term percentages were calculated. They should not be treated as mutually exclusive categories or added together.
Other adverse events are listed for 11 participants at risk in the 400 µg arm and 12 at risk in the 200 µg arm. The record does not give definitions or further detail for these other events in the registry record for this interpretation. Deaths are not reported in the adverse-event entry, which does not establish that no deaths occurred.
These counts describe events recorded during the study; they do not establish causation or provide a comparative safety analysis. The registry record does not report event timing, severity beyond the serious classification, exposure-adjusted rates, or statistical uncertainty for the arm counts.
12. What the Result Does, and Does Not, Mean
The results describe a phase 1 pharmacokinetic study of two brimonidine tartrate implant doses in patients undergoing pars plana vitrectomy. The primary reported values are arm-specific maximum vitreous concentrations by the 60-day timeframe: 137.0 ng/mL for the 400 µg implant and 34.9 ng/mL for the 200 µg implant. The registry reports no inferential analysis for comparing them.
These measurements can be used to describe the largest recorded vitreous concentration in each arm. They do not show the typical concentration, the full concentration-time profile, the degree of variability between participants, or the precision of a dose contrast. Without individual observations and uncertainty estimates, readers cannot establish whether the maxima reflect a general pattern or a small number of extreme measurements.
The results do not establish a clinical benefit, and they do not answer whether a treatment improves an outcome of interest to patients. The primary endpoint is a pharmacokinetic measurement, not a reported clinical efficacy endpoint. The registry's secondary outcomes concern aqueous humor and plasma measurements, but their results are not reported in the registry record.
The study is labeled randomized and double masked, but the record does not report enough detail to evaluate how those procedures were implemented or how they informed the analysis. The primary endpoint is described for a per-protocol population with pharmacokinetic data available. The reasons for the endpoint analysis counts and the handling of missing measurements are not reported.
The adverse-event entries are also descriptive. They show the recorded serious-event counts and selected event terms, but do not provide an inferential safety comparison. The record does not establish that events were caused by an implant. It also does not report deaths in the available adverse-event details; absence of a death count should not be read as confirmation that there were no deaths.
Overall, the registry supports a narrow account of observed maximum concentrations and recorded adverse events. It does not support conclusions about typical exposure, a statistically established dose difference, clinical effectiveness, or comparative safety.
13. Why This Trial Matters Statistically
This trial is statistically instructive because the form of a reported summary determines what can be concluded. The primary endpoint is an arm-level maximum, not a mean concentration or a modeled comparison. A maximum can answer a focused question about the largest observed level, but readers should not interpret it as the level experienced by a typical participant.
The example also shows why uncertainty matters. A value without a confidence interval, distribution, or other measure of spread gives little information about how stable the estimate might be. The record lists arm counts, but does not provide participant-level values or an analysis of the dose contrast. Thus, randomized assignment is not enough by itself to make the posted maxima an inferential result.
Another statistical lesson is the distinction between a study result and a planning illustration. The record's planning assumptions describe calculations based on the observed effect under specified hypothetical assumptions. Those calculations are not observed power, and they do not substitute for the trial's original design justification. The justification and prospective analysis plan are not reported in the registry record.
Finally, the record names secondary pharmacokinetic outcomes but does not report their results. Statistical interpretation depends not only on which outcomes were planned, but on which analyses and results are available, how missing data were handled, and whether multiplicity was addressed. Those details are not reported. This makes careful description more appropriate than extending the findings beyond the posted summaries.
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 primary result is a maximum per treatment arm. It does not describe the distribution of concentrations or provide a typical value, and the registry gives no measure of uncertainty for the maxima. The record does not indicate whether each participant had the same measurement schedule or how incomplete measurement series affected selection of the highest value.
The endpoint population is per protocol and is defined as participants with pharmacokinetic data available. The endpoint counts are 11 for the 400 µg arm and 12 for the 200 µg arm, while overall enrollment is 24. Participant flow, reasons for exclusions or unavailable data, and methods for handling missing measurements are not reported in the registry record.
The timing description allows vitrectomy 2, 4 or 8 weeks after implant administration, but the record does not explain how timing was allocated or incorporated into the analysis. It does not report whether the dose arms were balanced by timing, or provide results by timing category. This limits interpretation of how measurement timing relates to the observed arm maxima.
The registry lists two secondary outcomes but does not report their results in the registry record for this analysis. It also lists no statistical analyses for the primary endpoint. Details of randomization, masking, protocol deviations, sample-size justification, interim analyses, and the statistical plan are not reported in the registry record.
Safety reporting is limited to listed counts and selected serious-event terms. The record does not provide event-level detail, timing, attribution, or a comparative statistical analysis. These limitations constrain both interpretation of the pharmacokinetic summaries and assessment of safety differences between arms.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics of the Brimonidine Tartrate Posterior Segment Delivery System in Patients Undergoing Pars Plana Vitrectomy — NCT01229410.
- Registry record last updated 2013-08-05; status last verified 2013-07.
- Results first posted 2013-08-05.
- 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.
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18. Record Summary
NCT01229410 is a completed phase 1 randomized, double-masked, parallel study sponsored by Allergan. It enrolled 24 patients undergoing pars plana vitrectomy and compared a 400 µg brimonidine tartrate implant with a 200 µg implant. The registry records a study start of 2010-12 and primary completion of 2011-05.
The primary outcome is the highest vitreous humor brimonidine level in the study eye by the 60-day timeframe, in a per-protocol population with pharmacokinetic data available. The reported arm maxima are 137.0 ng/mL for the 400 µg arm and 34.9 ng/mL for the 200 µg arm. No comparative analysis is reported.
Two secondary outcomes are listed, but their results are not reported in the registry record. Serious adverse-event counts are listed as 1 participant in the 400 µg arm and 2 in the 200 µg arm, with 12 at risk in each arm. The record does not report a statistical safety comparison or enough detail to interpret those counts as causal or comparative evidence.