A 6-Month Extension Study of OTO-104 in Meniere's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A 6-Month Extension Study of OTO-104 in Meniere's Disease (NCT02706730), a na phase 3 study. The primary outcome is Otoscopic Examination - Tympanic Membrane Perforation at Week 24 (Month 6).

2. Clinical Question

This is a safety-focused extension question, rather than a randomized comparison of OTO-104 with another treatment or with no treatment. The stated reason for assessing the eardrum at the end of follow-up was to understand whether a tympanic perforation resulting from the intratympanic injection persisted at the end-of-study visit. The outcome is a participant count, not a measure of symptom change or a direct estimate of comparative treatment effect.

Eligibility depended on completion of either Otonomy study 104-201102 or 104-201506. The record does not give further detail about the characteristics of the participants who entered the extension, or how those who did not enter differed from those who did. The available registry information therefore frames the clinical question around end-of-study perforation status in the extension population, without establishing how the observed outcome would compare with a concurrent control group.

3. Trial Design

The registry describes a Phase 3, multicenter, open-label extension safety study of OTO-104 in subjects with unilateral Meniere's disease. It lists a single-group model, no masking, and allocation as NA. Thus the record does not describe random assignment or a blinded comparison between treatment groups. Participants had to complete one of the specified earlier Otonomy studies before entering the extension.

The planned regimen was a single intratympanic injection of OTO-104 given every 3 months for a total of 2 injections. The intervention description identifies OTO-104 as 12 mg dexamethasone. The study's stated duration was 6 months, with the primary outcome assessed at Week 24 (Month 6). Otoscopic examinations were conducted at each visit, according to the outcome description.

The registry lists 189 participants as enrolled. It records a start of 2016-02, primary completion in 2017-09, and status as terminated. The reason for termination is not reported in the registry record. The record does not state whether termination affected follow-up, outcome collection, or analysis, so those consequences should not be inferred.

As an extension study, this design addresses outcomes during continued observation after completion of an earlier Otonomy study. It does not furnish a contemporaneous control group for separating the course of the condition from changes occurring during the extension. Open-label status also means that the record does not indicate masking of participants or study personnel. The registry does not report the detailed operational procedures used to deliver treatment or collect and adjudicate endpoint data.

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 study was terminated early based on results of study 104-201506, a US Phase 3 study that indicated no statistically significant difference in the primary endpoint of reduction in definitive vertigo days (DVD) for OTO-104 vs placebo nor for any of the secondary endpoints. Decision was made to terminate all ongoing studies on August 31, 2017, including this study. At the time of termination, 156 subjects completed the study through Month 3 and 121 subjects completed the study through Month 6.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The 6-month Safety Analysis Set included all subjects who received at least 1 dose of study drug and completed the study at the Month 6 visit.

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 Analysis Set included all subjects who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Otoscopic Examination - Tympanic Membrane Perforation at Week 24 (Month 6), measured over 6 Months.

The primary endpoint is the number of participants with tympanic membrane perforation at Week 24 (Month 6). The record describes otoscopic examinations at each visit and states that the endpoint was intended to address whether a perforation resulting from the intratympanic injection persisted at the end-of-study visit. It is a binary outcome at the participant level: each participant either met the endpoint definition or did not, as assessed at the specified visit.

A count can be useful for describing how often a defined event was observed in a safety population. The endpoint's clinical focus is persistence at the end of follow-up, rather than simply whether an examination at any earlier visit detected a perforation. However, the registry record does not provide the number meeting this endpoint, its denominator for the primary analysis, or an estimate of uncertainty. It therefore does not allow the event frequency or its precision to be described.

The defined 6-month Safety Analysis Set included subjects who received at least 1 dose of study drug and completed the study at the Month 6 visit. That population definition is important: it is not necessarily interchangeable with all enrolled participants. The registry record does not report how many participants were included in that set or how participants without a Month 6 examination were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count describe?

The primary outcome is recorded as a count of participants with an event. In general, this type of endpoint reduces each person's status at the specified assessment to an event or no event. A count is straightforward to understand, but interpretation also depends on the denominator: the number of participants eligible for the analysis and actually assessed. A count alone does not express the frequency of the event unless the relevant denominator is known. The registry record does not report the primary endpoint count or its analysis denominator.

For a binary outcome, an analysis might report a proportion and an interval expressing uncertainty. A confidence interval is a range of values compatible with the data and the method used to calculate it; its width reflects how precisely the quantity has been estimated. This is a general statistical explanation, not a description of an interval reported for this study. No primary endpoint interval is reported in the registry record, so its precision cannot be assessed.

What can a single-group design estimate?

A single-group study can describe the events recorded among participants receiving the study intervention. Without a concurrent comparator, it cannot estimate a between-group treatment contrast. The observed event experience may reflect the intervention, the underlying condition, other care, participant characteristics, or other factors; a single-group result cannot isolate those explanations. This is a general design limitation, not evidence that any particular factor affected this study.

Open-label means that masking is listed as none. In general, knowledge of treatment assignment can influence reporting, examination, or decisions about recording outcomes, depending on the outcome and procedures. The endpoint was assessed by otoscopic examination, but the registry record does not describe assessor masking, adjudication, or other safeguards against bias. It would therefore be inappropriate to assume either that assessment was biased or that it was protected from bias.

How should significance testing be understood?

A p-value, when reported, quantifies how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. No primary endpoint test or p-value is reported in the registry record. In a single-group safety study, a test against a hypothetical reference value would also require a clearly stated reference and analysis plan; neither is reported.

The planning illustrations associated with the study use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not reported features of this trial's design. In particular, equal allocation between two arms does not describe the listed single-group study. The registry record does not report the trial's own sample-size justification, and no planning illustration should be read as observed power or as evidence about the primary outcome.

Why do assumptions matter for binary data?

Methods for binary outcomes generally rely on assumptions about how participant outcomes vary and how observations are related. For example, an analysis may treat participants' outcomes as independent, while shared study sites or other common factors could in some settings make observations more alike. Whether that issue applies, and how it should be handled, depends on the design and analysis. The registry record identifies the study as multicenter but does not report an adjustment for site, a model, or an assessment of such assumptions.

Over-dispersion is a general term for variability greater than a model expects. If present, it can make standard errors too small and intervals too narrow when the model does not account for it. The registry record does not report a model or diagnostics for over-dispersion. It is not possible to determine from the record whether this issue arose or was relevant to the primary endpoint analysis.

What can be concluded without a posted analysis?

Statistical interpretation requires the result, its analysis population, and enough methodological detail to understand how it was obtained. Here, the registry provides the endpoint definition and population definition, but no primary outcome analysis. It also lists no analyses. Accordingly, no estimate, interval, or test can be evaluated, and no recalculation from posted primary summary statistics is possible. General statistical concepts explain what such quantities would mean if reported; they do not fill in the missing study result.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or analyses are examined: the chance of at least one apparently notable result can increase as the number of statistical tests grows. Methods such as prespecifying a primary analysis or adjusting for multiple tests can address that issue, depending on the study question. The registry lists one outcome measure and no analyses. It does not report a multiplicity strategy, a hierarchy of outcomes, or whether additional outcomes were assessed but not posted. The absence of that information does not establish that multiplicity was or was not addressed in the study's conduct.

The primary population is described as the 6-month Safety Analysis Set: subjects who received at least 1 dose of study drug and completed the study at the Month 6 visit. This definition excludes, by its wording, participants who did not complete that visit, but the registry record does not report the number excluded or the reasons for noncompletion. It also does not report missing-data methods, imputation, sensitivity analyses, or how an unavailable otoscopic assessment was classified.

That distinction matters because completion-based analysis can describe participants with observed Month 6 status without necessarily describing all enrolled participants. If missing outcomes are related to participants' health or event status, the observed set could differ from the full enrolled group. This is a general consideration, not a claim about the missingness pattern in this study. The registry gives neither enough detail to assess missingness nor a primary result to check against alternative assumptions.

The registry's 189 enrolled participants and the 189 listed at risk in the adverse event group should not be treated automatically as the denominator for the primary endpoint. The record defines a specific primary safety population but does not report its size. Accordingly, neither the primary event frequency nor the impact of missing endpoint data can be derived from the available information.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hemiplegic migraine (0.5%), omental infarction and small intestinal obstruction (0.5%), acute myeloid leukemia (0.5%), angina pectoris (0.5%), deafness, unilateral (0.5%).

The registry lists 189 participants at risk for serious adverse events in the OTO-104 group, with 7 affected. It lists 189 at risk for other adverse events, with 30 affected, and records 1 death. These are counts from the adverse event information, not comparative estimates. The record does not state whether the death was considered related to treatment, or provide the timing or circumstances of the death.

The serious-event terms listed are Hemiplegic Migraine, Omental Infarction and Small Intestinal Obstruction, Acute Myeloid Leukemia, Angina Pectoris, Deafness, Unilateral, and Prostate Cancer. Each is reported as 0.5%. The registry excerpt does not establish whether these terms represent distinct participants, how events were judged related to study drug, or what follow-up period applies to each term. These details should not be inferred from the percentages.

Because the study has no control group, the counts do not show how event occurrence compares with another treatment or with no study treatment. They also do not establish causation. The figures describe what the registry lists for the study group; the record does not provide uncertainty estimates or a full account of event severity, timing, or attribution.

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

The study record describes an open-label extension in which participants received OTO-104 on a schedule of injections at 3-month intervals for a total of 2 injections. Its primary endpoint concerns tympanic membrane perforation at the Month 6 visit, and its stated purpose is to understand persistence of a perforation at the end of follow-up. The registry also gives adverse event counts for the OTO-104 group.

However, the primary outcome result is not reported in the registry record. No primary endpoint count or analysis is available to show how many participants experienced perforation, what denominator was analyzed, or how precisely the event frequency was estimated. The record's stated endpoint and its rationale are not themselves findings. The listed adverse event counts do not substitute for the missing primary outcome result.

The design does not provide a control group, so even a complete event count would describe outcomes in the extension group rather than establish a comparative treatment effect. Open-label status and selection of participants who completed an earlier study are also relevant to interpretation. The registry does not report enough information to determine how these features affected outcome measurement or the population represented.

The serious adverse event counts, other adverse event count, and death count are descriptive. They do not establish that OTO-104 caused or prevented any event. The record does not report event attribution, comparative rates, or uncertainty estimates. The termination status is recorded, but its reason and implications for the analysis are not reported in the registry record.

Thus, the record supports a description of the intended safety question, design, and listed adverse event counts. It does not support a conclusion about the observed primary endpoint result, its precision, or a causal or comparative effect.

13. Why This Trial Matters Statistically

This study illustrates an important distinction between an endpoint being named and an endpoint result being available. The registry specifies a concrete safety question—whether tympanic membrane perforation was present at Week 24 (Month 6)—and describes the population intended for that assessment. Yet the registry does not report the outcome count or an analysis. Without those elements, readers cannot estimate the event frequency or its precision.

The design also clarifies what an extension study can and cannot answer statistically. A single-group follow-up can document events observed during continued treatment and observation. It cannot, without a concurrent comparator, determine how those events differ from outcomes under another treatment or from the course of the condition without the study intervention. This distinction remains important even when the study is multicenter and Phase 3.

The population definition matters as well. The primary safety set requires receipt of at least 1 dose and completion of the Month 6 visit. That is narrower by definition than a population based solely on enrollment. Since the record does not give the size of this set or explain missing endpoint data, the relation between the enrolled group and the primary analysis population cannot be assessed.

Finally, the planning assumptions described for sample-size illustrations should not be confused with the design of this trial. They specify equal allocation between two arms, whereas the registry describes a single-group study. Planning calculations can help frame hypothetical future research, but they do not replace an observed result and should not be interpreted as evidence of power achieved in this study.

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 endpoint result and analysis are not reported in the registry record. This prevents assessment of the endpoint count, denominator, estimated event frequency, or statistical precision. The record also does not report the size of the defined 6-month Safety Analysis Set, so the primary analysis population cannot be quantified from the enrollment figure alone.

There is no comparator group, and the study is open-label. The record therefore offers no randomized estimate of a treatment contrast, and it does not report masking of outcome assessors or endpoint adjudication procedures. These design features limit the conclusions that could be drawn even if the primary count were available.

Participants had to complete either of two earlier studies to be eligible for the extension. The registry does not report characteristics of eligible participants who did not enroll, or explain how participants entering the extension differed from the original study populations. This limits assessment of selection and generalizability. The study is also listed as terminated; the reason and any effect on follow-up or data availability are not reported in the registry record.

For the primary endpoint, the record does not describe missing-data handling, sensitivity analyses, statistical methods, or any adjustment for study site. It also does not provide a sample-size justification for the trial. The serious adverse event listing lacks comparative context, and event relatedness and timing are not reported. These omissions prevent stronger interpretation of the outcome and safety information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A 6-Month Extension Study of OTO-104 in Meniere's Disease — NCT02706730.
• Registry record last updated 2022-12-14; status last verified 2022-11.
• Results first posted 2022-12-14.
• 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 describes NCT02706730 as a Phase 3, multicenter, open-label, single-group extension safety study of OTO-104 in unilateral Meniere's disease. The regimen was 12 mg dexamethasone by intratympanic injection at 3-month intervals for a total of 2 injections. Eligibility required completion of one of two earlier Otonomy studies. The record lists 189 enrolled participants and a terminated status.

The primary endpoint is the count of participants with tympanic membrane perforation at Week 24 (Month 6), in a Safety Analysis Set defined by treatment receipt and Month 6 completion. The primary result and analysis are not reported in the registry record. The adverse event listing records 7 participants affected by serious adverse events, 30 by other adverse events, and 1 death, among 189 at risk in each listed category. No comparator is reported, and event causality is not established by these counts.