SPI-1005 for the Treatment of Meniere's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SPI-1005 for the Treatment of Meniere's Disease (NCT04677972), a randomized phase 3 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events.

2. Clinical Question

The randomized, double-blind, placebo-controlled study was designed to evaluate the safety and efficacy of SPI-1005 in people with Ménière's disease, with an open-label extension intended to evaluate chronic safety. The central comparison in the randomized portion is SPI-1005 against matching placebo. The posted primary outcome, however, is a safety measure: the number of participants with treatment-emergent adverse events (TEAEs). The listed secondary outcomes concern changes in tinnitus severity, tinnitus loudness, vertigo severity, aural fullness, and dizziness.

That distinction matters when interpreting the results. Safety counts describe participants with adverse events; they are not, on their own, an efficacy comparison for symptoms. The registry record includes counts of participants with serious and other adverse events, but it does not provide a single inferential comparison for the primary endpoint or results for the listed symptom outcomes. Thus, the record supports a descriptive reading of the posted safety information, not a conclusion about symptom benefit or the overall balance of benefits and harms.

3. Trial Design

This is a phase 3, randomized, double-blind, placebo-controlled, multi-center study with a parallel design. The registry identifies masking as quadruple. It does not report which specific roles were masked, so the masking label alone cannot establish whether participants, clinical staff, outcome assessors, or other groups knew the assigned treatment. The sponsor is Sound Pharmaceuticals, Incorporated.

The active-treatment arm is listed as SPI-1005 400 mg BID, given orally for 28 days, with 84-day follow-up. The comparator arm received matching placebo BID for 28 days, also with 84-day follow-up. The registry lists 220 participants enrolled and posts group counts of 112 for SPI-1005 and 108 for placebo in the adverse-event results. The record does not report the allocation ratio as a protocol detail, nor does it explain how the posted counts relate to any analysis population.

The study began on 2022-08-02, reached primary completion on 2023-09-19, and is listed as completed. Its brief description specifies adults with definite Ménière's disease and active symptoms within three months preceding enrollment. The official title also describes an open-label extension intended to evaluate chronic safety. A separate extension group is posted as Open Label Extension: SPI-1005 400 mg BID, with 197 participants at risk in the safety results. The registry record does not explain participant movement into that extension group or whether its participants overlap with the randomized groups.

Open-label means treatment assignment is not masked in that extension, but the record does not report further operational details. The randomized comparison and extension therefore have different interpretive contexts: the former has a placebo group and masking designation, while the extension is described as open label. Safety counts from these groups should not be treated as if they arose from the same comparison.

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.

Randomized Controlled Trial (RCT)

Reasons for not completing this period:

Open Label Extension (OLE)

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events, measured over 84 days.

The primary endpoint is the number of participants with treatment-emergent adverse events during the 84-day timeframe. A participant count is a safety summary: it records how many people experienced an event, rather than the total number of event episodes. The registry describes the outcome as a count of participants and does not provide a more detailed definition of treatment-emergent, such as the rules used to determine onset or attribution.

Safety endpoints are used to characterize unwanted events observed during treatment and follow-up. A participant-based measure can help readers understand how many people were affected, while additional information about event seriousness, type, timing, and attribution is needed to interpret the clinical context. General statistical interpretation: a count alone does not show how precisely an underlying event frequency has been estimated, and it does not establish that treatment caused an event. A comparison between treatment groups also needs a clearly defined analysis, including which participants are included and how uncertainty is quantified.

The registry posts serious and other adverse-event counts for the randomized groups and the open-label extension. It does not post a single comparative statistical result for the named primary endpoint. Nor does the record define how events were classified as treatment-emergent or report the analysis population used for that endpoint. The listed symptom outcomes are secondary outcomes and are not substitutes for the primary safety measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical challenge is that the named primary outcome is a participant count, while the registry record does not post a single comparative result for it. The outcome title refers to the number of participants with treatment-emergent adverse events, and its timeframe is 84 days. The safety results separately show participant counts for serious and other adverse events. Without a reported endpoint definition and analysis, it is not possible to determine whether those categories map exactly to the primary outcome or how the primary analysis combined event types.

What does a participant count represent?

A participant count records the number of people who experienced at least one event within the defined outcome. It differs from an event count, which can include multiple episodes in the same person. General statistical explanation: when the outcome is binary at the participant level, each person is classified as having or not having the event under the analysis definition. A group comparison may then estimate an absolute difference or a relative measure, but the choice depends on the analysis plan. No such comparative estimate is posted for this primary endpoint.

The adverse-event record includes participants at risk and participants affected in the randomized groups and extension. Those figures are useful for understanding the posted summaries, but they do not supply an analysis method or uncertainty estimate. A confidence interval, when reported, describes the range of values compatible with the data under the specified model and assumptions. The registry record does not report confidence intervals for the primary endpoint. A p-value, if reported, would address compatibility with a specified null model; no p-value for this endpoint is posted.

Why does the analysis population matter?

Randomized trials can report results for different populations, such as all randomized participants or participants who received treatment, but the rules for defining those groups must be stated. The registry record does not report the analysis population for the primary outcome, exclusions from analysis, or how missing outcome information was handled. The group counts in the safety results should therefore be described as posted at-risk counts, not assumed to define an unreported primary analysis population.

The trial is randomized and parallel, and the registry identifies quadruple masking. In general, randomization helps make treatment groups comparable at baseline on average, while masking can reduce certain forms of bias. These design features do not remove the need to report an analysis plan, outcome definitions, missing-data handling, and uncertainty. The record does not identify the roles covered by quadruple masking or provide a detailed statistical analysis plan.

How should the extension be treated?

The open-label extension is described as an evaluation of chronic safety. Its posted group has 197 participants at risk, with counts for serious and other adverse events. General statistical explanation: an open-label group without a concurrent randomized comparator is mainly descriptive because changes over time may reflect factors other than treatment, including selection into extension participation and the course of the condition. The registry does not report the extension eligibility rules, participant overlap, or a comparative analysis. Its counts should not be combined with the randomized groups or treated as a randomized treatment contrast.

What can sample-size illustrations say?

Any sample-size illustration associated with the posted results is planning information, not observed power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm. These assumptions describe a hypothetical planning exercise; they do not establish the trial's original sample-size rationale or prove that the study had adequate power for a particular endpoint.

The registry record does not report the protocol's sample-size justification, the assumptions used when the trial was designed, an interim-analysis plan, or a detailed statistical analysis plan. It also does not report a numerical primary-outcome comparison to which a precision assessment could be attached. The sample-size assumptions should therefore not be confused with evidence that an effect was detected or ruled out.

General statistical explanation: adverse-event data can be sparse, especially for serious events. In sparse data, estimates may be imprecise, and conventional approximations may not perform well. Over-dispersion is a concern in count models when variability exceeds the model's assumptions; assessing it requires data and a stated model. The registry does not report a count model, an over-dispersion assessment, or any alternative method. These are considerations for interpreting a possible analysis, not methods that can be attributed to this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and identifies secondary outcomes involving tinnitus severity, tinnitus loudness, vertigo severity, aural fullness, and dizziness. It does not report how many statistical hypotheses were tested, which outcomes were included in a confirmatory testing sequence, or whether any adjustment for multiple comparisons was used. Without those details, the status of the secondary outcomes as exploratory or confirmatory cannot be determined from the registry record.

Multiplicity arises when several outcomes, time points, or comparisons are assessed. General statistical explanation: as the number of statistical tests increases, the chance of at least one apparently unusual result can increase if the tests are interpreted without accounting for their joint testing context. Methods such as hierarchical testing or adjustment of significance thresholds can address this, but the registry record does not report that either approach was used.

The record lists zero analyses. It does not report a statistical analysis population for the primary endpoint, the handling of missing outcome data, methods for censoring or follow-up gaps, or rules for participants who discontinued. It also does not describe imputation, sensitivity analyses, or whether all randomized participants were included. These omissions limit assessment of how robust any outcome estimate would be to missingness or analysis choices.

The adverse-event counts are descriptive, but the record does not state whether all participants were monitored for the same duration or how partial follow-up was handled. The randomized treatment period is listed as 28 days with 84-day follow-up, while the primary endpoint timeframe is 84 days. The record does not provide further detail on event collection windows or endpoint adjudication. The open-label extension is a separate setting, and its analysis population and relationship to the randomized phase are not reported.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypoacusis (0.9%), diverticulitis (0.9%), nausea (0.5%), vomiting (0.5%), ankle fracture (0.5%).

For serious adverse events, the posted randomized-group counts are 2 affected participants among 112 at risk in the SPI-1005 400 mg BID group and 0 among 108 at risk in the placebo group. The open-label extension lists 4 affected participants among 197 at risk. The registry reports 0 deaths in all three groups. These are participant counts, not counts of all event episodes.

For other adverse events, the posted affected-participant counts are 25 in the SPI-1005 group, 19 in the placebo group, and 90 in the open-label extension. The registry lists six serious adverse-event terms with percentages: Hypoacusis and Diverticulitis at 0.9% each, and Nausea, Vomiting, Ankle fracture, and Depression at 0.5% each. The record does not provide further event-level detail alongside those terms.

General statistical explanation: serious events may be uncommon, so small counts can be compatible with substantial uncertainty. A count does not identify whether an event was caused by treatment, and a zero observed count does not prove that the underlying risk is zero. The registry does not report a comparative safety estimate or confidence interval for these figures. The extension is open label and has no concurrent placebo group in the posted results, so its counts have a different interpretive context from the randomized groups.

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

The posted results describe adverse events among participants in the randomized groups and the open-label extension. They show 2 participants with serious adverse events in the SPI-1005 group and 0 in the placebo group; other adverse-event counts are 25 and 19, respectively. The extension lists 4 participants with serious adverse events and 90 with other adverse events. No deaths are listed in any of the three groups. These statements describe the registry entries and do not establish causation.

The record does not provide an inferential comparison for the primary endpoint, such as an effect estimate with a confidence interval. It also does not post results for the listed secondary symptom outcomes. Therefore, the safety counts cannot be used to conclude whether SPI-1005 changes tinnitus, vertigo, aural fullness, or dizziness. Nor does the absence of a reported efficacy analysis mean that no effect occurred.

A difference in raw counts is not itself a complete statistical comparison. Interpretation depends on the endpoint definition, the analysis population, follow-up completeness, and a method for estimating uncertainty. The registry does not report these details for the primary outcome. The extension is open label and its participants' relationship to the randomized study is not described, so its safety counts should not be treated as a direct randomized comparison.

The study's completed status and posted safety entries indicate that the registry contains outcome information, but completion does not fill in unreported analytic details. The record does not report the trial's sample-size justification, interim analyses, or full statistical plan. Overall, these data allow a limited descriptive account of reported adverse events. They do not, by themselves, establish treatment effects, prove equivalence between groups, or provide a complete safety or efficacy assessment.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a named outcome and a fully reported analysis. The primary endpoint is a participant count for treatment-emergent adverse events over 84 days, while the registry posts separate serious and other adverse-event summaries. Without a single comparative analysis and an explicit link between these summaries and the primary endpoint, readers should not treat the posted counts as a complete test of the primary question.

The randomized, placebo-controlled design provides a framework for comparison, and the registry reports group counts for both randomized arms. The open-label extension adds longer-term safety context, but its design and relationship to the randomized participants are not described in enough detail to treat it as a controlled comparison. Keeping these settings distinct is important when interpreting the figures.

The record also illustrates why uncertainty and analysis populations matter. Counts, even when accompanied by at-risk totals, do not show the precision of a treatment contrast. No confidence interval, p-value, or primary-outcome analysis is reported. The lack of information about missing data, multiplicity, and the analysis population further limits assessment of what the posted outcomes can support.

For clinical researchers and statisticians, the practical lesson is to separate descriptive safety reporting from inferential conclusions and from efficacy outcomes. The listed symptom measures do not have posted results in the registry record. The available safety counts are worth describing accurately, while avoiding claims that require analyses or outcome information that the record does not report.

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.

Several trial-specific details needed for a fuller statistical assessment are not reported in the registry record. These include the primary endpoint's operational definition, the analysis population, the handling of missing data, the statistical model, and an inferential comparison. The record lists zero analyses and does not provide confidence intervals or p-values for the primary outcome.

The relationship between the primary endpoint and the serious and other adverse-event categories is not explained. The registry does not report event attribution rules or further event-level context for the serious-event terms. Its adverse-event summaries therefore support description of the posted counts but not a determination of treatment causality.

The extension group is listed separately, but participant overlap with the randomized phase, extension entry criteria, and follow-up details are not reported. The open-label setting also differs from the masked randomized comparison. These factors limit direct comparison of the extension counts with the randomized groups.

The registry lists secondary symptom outcomes but does not report their results in the record. It does not describe multiplicity handling, interim analyses, or the protocol's sample-size justification. The posted enrollment and group counts do not replace those missing design and analysis details. As a result, the record allows a narrow descriptive reading of safety information, rather than a comprehensive assessment of statistical precision or treatment effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: SPI-1005 for the Treatment of Meniere's Disease — NCT04677972.
• Registry record last updated 2026-07-23; status last verified 2026-06.
• Results first posted 2026-06-26.
• 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

NCT04677972 is a completed phase 3, randomized, double-blind, placebo-controlled, multi-center, parallel study of SPI-1005 in adults with definite Ménière's disease and active symptoms within three months preceding enrollment. The registry lists 220 participants enrolled. The randomized treatment arms received oral SPI-1005 400 mg BID or matching placebo BID for 28 days, with 84-day follow-up. An open-label extension is also described.

The primary outcome is the number of participants with treatment-emergent adverse events over 84 days. Posted safety counts include serious and other adverse events, as well as zero deaths in the randomized groups and extension. The registry does not report a single comparative analysis for the primary endpoint, results for the listed symptom outcomes, or key details of the statistical analysis plan, analysis population, and missing-data handling. The posted data therefore support descriptive safety reporting but not a complete inferential or efficacy assessment.