An Open-label Extension Study to Evaluate the Safety of the 13 mg Bimatoprost Ocular Insert: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-label Extension Study to Evaluate the Safety of the 13 mg Bimatoprost Ocular Insert (NCT02537015), a na phase 2 study. The primary outcome is Percentage of Participants With Ocular and Non-ocular Adverse Events (AE) by Severity.

2. Clinical Question

This is a safety question about events observed during continued exposure to the insert in an extension-study population. It is not a randomized test of the insert against another treatment or against no treatment. The primary endpoint was intended to describe the proportion of participants with adverse events and their severity; numerical results for that endpoint are not reported in the registry record. Separately, the posted safety figures include participants with serious adverse events and participants with other adverse events. Those figures describe reported safety outcomes, but do not establish how the insert compares with an alternative.

3. Trial Design

This was a Phase 2, open-label extension study of the 13 mg Bimatoprost Ocular Insert. Its official title identifies the intended participants as people with open-angle glaucoma or ocular hypertension who had completed study FSV5-004. The registry record lists a single-group model, allocation as not applicable, and no masking. Enrollment was 81, and the study status is completed.

All participants received the insert. The arm description specifies continuous use of a 13 mg insert in each eye for 12 weeks, followed by replacement with a new insert in each eye for another 26 weeks. The brief summary describes this as approximately 3 months followed by approximately 6 months, and characterizes the evaluation as long-term safety over 9 months. The primary endpoint timeframe runs from baseline, defined as Day 0 at enrollment in this study, to the end of the study at Week 38.

The study began on 2015-08-10, and primary completion was 2016-08-11. The sponsor was ForSight Vision5, Inc. Because the design has no randomized comparator, differences between treatment groups cannot be estimated from this study. The extension population also consists of participants who completed the earlier study, so the findings describe this selected group rather than an unselected population of people with these conditions.

The registry record does not report a protocol rationale for the study design, a sample-size justification, or a detailed statistical analysis plan. The registry record’s planning assumptions describe illustrative sample-size calculations, not the original trial design or observed power.

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: Participants who completed the Phase 2 study FSV5-004 \[NCT02358369\] were eligible to enroll in this open-label extension study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population included all enrolled participants who had at least one 13 mg Bimatoprost Ocular Insert placed.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The safety population included all enrolled participants who had at least one Bimatoprost Ocular Insert 13 mg placed.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Ocular and Non-ocular Adverse Events (AE) by Severity, measured over Baseline (Day 0, enrollment in this study) to end of study (Week 38).

The primary endpoint is the percentage of participants with ocular and non-ocular adverse events, categorized by severity. An ocular adverse event occurred in the eye; a non-ocular event occurred outside the eye. The registry record defines an adverse event broadly as an untoward medical occurrence during the study, whether or not it was suspected to be caused by the study treatment.

Severity was assessed by the investigator using the worst severity of each event. Mild meant the participant was aware of a sign or symptom but readily tolerated it; moderate meant discomfort interfered with usual activity; severe meant the event was incapacitating, with inability to work or do usual activity. These categories describe intensity and impact as defined in the record. They should not be treated as interchangeable with the separate classification of an event as serious.

A participant percentage is a descriptive safety measure: it indicates how many participants in the relevant population experienced an event during the specified observation period. It is useful for describing the frequency and severity distribution of events during exposure. Without a comparator group, however, it does not show whether event frequency differs from what would have occurred under another treatment or without the insert. Numerical results for the primary endpoint by severity are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary measure as a percentage of participants with an event, a binary outcome summarized descriptively. It does not report a statistical analysis for that endpoint. The concepts below are general explanations of how this type of outcome is commonly read; they are not claims about unreported analyses in this study.

What does a participant percentage describe?

For a binary safety outcome, each participant is classified according to whether the specified event occurred during the observation period. A proportion is the number of participants meeting that definition divided by the number in the analysis population, and a percentage expresses that proportion on a percentage scale. In this study, the primary outcome is defined by event location and severity, and the timeframe is baseline at Day 0 through Week 38. A participant-level percentage is different from an event count: a participant may experience more than one event, while a participant percentage generally counts whether each participant experienced the specified outcome. The registry record does not provide a detailed counting rule for recurrent events in the primary endpoint.

Why distinguish severity from seriousness?

Severity describes the intensity or impact of an event. The study record gives investigator-assessed categories of mild, moderate, and severe. Seriousness is a separate safety classification. In general, an event can be serious without being described as severe, and an event described as severe is not automatically a serious adverse event. The registry record’s serious-event summaries therefore answer a different descriptive question from the primary endpoint’s severity categories. The record does not provide additional study-specific criteria for classifying serious events.

What does an uncertainty interval add?

As a general statistical concept, a confidence interval gives a range of estimates compatible with the observed data under a specified method and its assumptions. A narrow interval indicates greater precision than a wide interval, while neither interval width nor the point estimate alone establishes cause. For a participant percentage, uncertainty depends in part on the number of participants and the number with the outcome. No confidence interval for the primary endpoint is reported in the registry record, so its statistical precision cannot be assessed from that endpoint in the record.

Why does the lack of a comparator matter?

A single-group study can describe the frequency of outcomes during the observed exposure period. A randomized comparison can additionally estimate a contrast between assigned groups, subject to its design and analysis assumptions. Here, the registry lists a single group, allocation as not applicable, and no masking. Consequently, no treatment-group contrast is available. Events recorded during follow-up may have multiple explanations, and the registry’s definition explicitly does not require a suspected treatment cause. The descriptive counts should not be interpreted as causal effects.

What do the planning assumptions mean?

The registry record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of an observed effect. These are assumptions for illustrative sample-size planning. The record also distinguishes planning calculations from the study’s own design and states that sample-size figures are not observed power. In general, sample-size planning asks how many participants would be needed for a future study under specified assumptions. It is not a measure of how likely the completed study was to find a result, and it does not replace an analysis of the actual observations. No numerical planning output or numerical observed primary effect is reported in the registry record.

The registry record lists 6 outcome measures and 0 analyses. It does not report a detailed inferential method for the primary endpoint, a model for repeated or recurrent events, adjustment for baseline characteristics, or a method for handling clustering between eyes. These methods cannot be inferred from the endpoint description alone. As a general principle, an analysis method needs to match both the outcome definition and the way observations were collected; without those details, the posted summaries are best read as descriptive safety information.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures and 0 analyses. It does not report a multiplicity procedure or explain whether any outcome was designated as a formal primary hypothesis test beyond the listed primary endpoint. Multiplicity arises when several outcomes or comparisons are examined: the more opportunities there are to find a statistically notable result, the more important it becomes to define in advance how those results will be interpreted. This is a general statistical concern, not evidence that an unreported adjustment was or was not performed.

The record also does not report an approach to missing data, participant withdrawals, or incomplete follow-up. This matters for a safety outcome because participants with less observation time may have fewer opportunities for an event to be recorded. Without follow-up completeness and missing-data details, the extent to which the percentages reflect the full intended period cannot be assessed. The safety population is defined as all enrolled participants who had at least one insert placed; the record does not provide more detail about exclusions or the handling of participants with partial exposure.

The primary endpoint timeframe is baseline at Day 0 to the end of study at Week 38, but the registry record does not specify how events with incomplete severity or location information were handled. It also does not state whether analyses were planned for subgroups or recurrent events. These features are not reported in the registry record and should not be assumed from the posted event summaries.

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: atrial fibrillation (1.2%), cholelithiasis (1.2%), hip fracture (1.2%), upper limb fracture (1.2%), fluid overload (1.2%).

The serious adverse-event summary reports 81 participants at risk and 7 affected. The other-adverse-event summary reports 81 at risk and 20 affected. These are distinct categories in the posted safety information; the registry record does not explain whether the groups of affected participants overlap. No additional participant totals should be inferred by combining them.

The listed serious-event terms are atrial fibrillation, cholelithiasis, hip fracture, upper limb fracture, fluid overload, and chronic obstructive pulmonary disease, each reported as 1.2%. The record does not report further event counts for these terms in the registry record for this account. These term-specific percentages are descriptive and do not establish causation. The registry’s general adverse-event definition includes events regardless of suspected cause.

Seriousness should also be distinguished from the primary endpoint’s mild, moderate, and severe categories. Those categories concern investigator-assessed severity; a serious adverse event is a separate classification. The record does not provide the primary endpoint’s numerical breakdown by severity, so the serious-event listing is not a substitute for that endpoint.

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

The posted results describe adverse events reported in an open-label extension study of the 13 mg Bimatoprost Ocular Insert. The participants had completed study FSV5-004, and the intervention schedule involved insert use for 12 weeks followed by replacement for another 26 weeks. The safety summaries report 7 affected participants for serious adverse events and 20 affected participants for other adverse events, each with 81 at risk. The listed serious-event terms are reported individually as 1.2%.

These figures do not show that the insert caused the events. The registry defines an adverse event as an untoward medical occurrence during the study regardless of suspected cause, and there is no randomized comparator against which to judge whether event occurrence differed. The figures also do not establish how the event experience would compare with another treatment, no treatment, or a broader population.

The primary endpoint was designed to measure ocular and non-ocular adverse events by worst severity from baseline through Week 38. Its numerical severity-specific results are not reported in the registry record. The serious-event information therefore does not answer the full primary question. The registry record also provides no confidence interval for the primary endpoint, so its precision cannot be judged from a reported interval.

As a general interpretation principle, safety findings from a single-group extension can identify events observed during follow-up and contribute descriptive information about tolerability in the studied participants. They cannot, on their own, determine comparative risk or establish that an event is attributable to treatment. The record’s status as completed indicates that the study is listed as completed; it does not resolve the missing endpoint details or remove limitations arising from the non-comparative design.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between describing safety and estimating comparative effects. An open-label, single-group extension can record events during continued exposure, but it has no randomized control group to separate treatment-related differences from background events, participant characteristics, or other influences. The event counts therefore need to be read as observations within the study rather than as a treatment contrast.

The outcome definitions also illustrate why endpoint labels matter. The primary measure concerns participant percentages by ocular or non-ocular location and worst severity, while the serious adverse-event summary is a separate classification. Treating those categories as interchangeable would misrepresent what each statistic describes. The primary endpoint’s numerical severity results are not reported in the registry record, making it especially important not to use the serious-event list as a proxy.

The extension design selects participants who completed an earlier study. That context is relevant to generalizability: the record describes the extension population, not necessarily all people with open-angle glaucoma or ocular hypertension. The registry’s safety population definition and the at-risk counts clarify the intended denominator, but the record does not provide follow-up completeness or missing-data handling.

Finally, the record demonstrates the difference between statistical planning and observed evidence. Planning assumptions can illustrate what a future design might require under specified conditions, but they are not a substitute for endpoint estimates, uncertainty intervals, or a comparative analysis. Here, the posted safety counts offer descriptive information, while the absence of numerical primary endpoint results and a comparator constrains the conclusions that can be drawn.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation is the single-group, open-label design. With allocation listed as not applicable and no masking, the study does not provide a randomized control comparison. Event counts can be reported for participants receiving the insert, but the record cannot establish whether these events were more or less common than under another condition or attribute them to the insert.

The study population is an extension population: participants had completed study FSV5-004. This may limit how broadly the findings apply beyond people eligible for and completing that earlier study. The registry record does not report further participant characteristics in the registry record for this account, so differences in population composition cannot be assessed.

The numerical results for the primary endpoint by severity are not reported in the registry record. Although serious and other adverse-event summaries are posted, they do not supply the missing severity-specific results. No confidence interval for the primary endpoint is reported, limiting assessment of precision. The record also does not report missing-data procedures, follow-up completeness, recurrent-event methods, or details about the treatment of partial exposure.

There are 6 outcome measures listed and 0 analyses. The registry record does not report a multiplicity strategy or a detailed statistical analysis plan. This leaves unclear how multiple outcomes were intended to be interpreted statistically. The record also does not report a sample-size justification for the original study; planning assumptions described as illustrations should not be treated as the study’s design rationale or observed power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Open-label Extension Study to Evaluate the Safety of the 13 mg Bimatoprost Ocular Insert — NCT02537015.
• Registry record last updated 2019-04-02; status last verified 2019-03.
• Results first posted 2019-02-26.
• 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.

18. Record Summary

The registry record describes NCT02537015 as a completed Phase 2, open-label extension study sponsored by ForSight Vision5, Inc. It enrolled 81 participants with open-angle glaucoma or ocular hypertension who had completed study FSV5-004. The study began on 2015-08-10, with primary completion on 2016-08-11.

Participants received a 13 mg Bimatoprost Ocular Insert in each eye continuously for 12 weeks, followed by a replacement insert for another 26 weeks. The primary endpoint was the percentage of participants with ocular and non-ocular adverse events by severity, from Day 0 through Week 38. Numerical primary endpoint results by severity are not reported in the registry record. The posted safety summaries report 7 participants affected by serious adverse events and 20 affected by other adverse events, with 81 at risk for each measure. The single-group design supports descriptive safety reporting, not a randomized treatment comparison.