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 Efficacy and Safety of AM-111 as Acute Sudden Sensorineural Hearing Loss Treatment (NCT02809118), a randomized phase 3 study. The primary outcome is Pure Tone Average (PTA).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02809118 |
| Phase | Phase 3 |
| Condition | Hearing Loss, Idiopathic Sudden Sensorineural |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 56 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Auris Medical, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People with severe to profound idiopathic sudden sensorineural hearing loss (ISSNHL). The registry record describes the condition and the intended population, but does not report a detailed eligibility profile or the characteristics of participants who enrolled.
Intervention
AM-111 gel for intratympanic use at concentrations of 0.4 mg/ml or 0.8 mg/ml. The trial sought to assess AM-111 for recovery of hearing after acute ISSNHL.
Comparator
Placebo gel for intratympanic use. The randomized design assigned participants among placebo and the AM-111 intervention arms; allocation details beyond the randomized designation are not reported in the registry record.
Primary question
Did hearing, measured as pure tone average (PTA), change between Day 0 before treatment and Day 91, and did that change differ across the randomized groups? The registry record states that the study was prematurely terminated and that no meaningful efficacy analysis could be performed.
The study's stated objective was to confirm AM-111's efficacy in recovery from severe to profound ISSNHL. The clinical question therefore concerns a change in hearing over time, assessed with pure tone audiometry, and a comparison of that recovery across the treatment groups. Word Recognition Score (WRS) was identified as the main secondary outcome.
The distinction between the planned question and the reported evidence is important. A randomized design can support a comparison between assigned groups when the planned data collection and analyses are completed. In this case, the registry record says that not all planned data were collected and that analyses were pre-specified not to be completed after premature termination. It does not report a treatment-effect estimate for PTA or WRS. As a result, the posted information does not establish whether hearing recovery differed between AM-111 and placebo.
3. Trial Design
This was a phase 3, randomized, quadruple-masked, parallel-group trial sponsored by Auris Medical, Inc. The interventions were AM-111 gel for intratympanic use at 0.4 mg/ml, AM-111 gel for intratympanic use at 0.8 mg/ml, and placebo gel for intratympanic use. The registry record reports enrollment of 56.
The study began in 2016-06, and primary completion was recorded as 2018-02. Its status is TERMINATED. These dates describe the registered study timeline; they do not establish that the planned follow-up or outcome collection was completed. The primary outcome timeframe is described as Day 0 and Day 91, with the added statement that the study was prematurely terminated.
Randomization is intended to make the assigned groups comparable on average, while masking is intended to limit the influence of knowledge about assignment on care, assessment, or reporting. Those are general features of these design elements, not evidence that this trial achieved balance or that masking was maintained. The registry record does not report the randomization method, allocation concealment procedure, or details of who was masked.
The parallel design means participants were assigned to an intervention group rather than being described as crossing between interventions. The record does not provide the treatment duration, dosing schedule, timing of intratympanic administration, or additional co-interventions. It also does not report a sample-size justification, stopping rationale, or whether any interim analyses took place. These details should not be inferred from the phase designation, enrollment, or termination status.
Although PTA and WRS are named as outcomes, the record states that planned data collection was incomplete and that no meaningful efficacy analysis could be performed. The main design question can therefore be described, but the registered outcome record does not supply a completed group comparison. Safety figures are reported separately and should not be treated as a substitute for the absent efficacy analysis.
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: In subjects assessed within the first 24 hours from Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL) onset, mean hearing threshold had to be confirmed by a second measure that was conducted, at the earliest, 24 hours after the onset of ISSNHL.
Overall Study
| Stage | Placebo | AM-111 0.4 mg/ml | AM-111 0.8 mg/ml |
|---|---|---|---|
| STARTED | 18 | 19 | 19 |
| COMPLETED | 18 | 18 | 18 |
| NOT COMPLETED | 0 | 1 | 1 |
Reasons for not completing this period:
| Reason | Placebo | AM-111 0.4 mg/ml | AM-111 0.8 mg/ml |
|---|---|---|---|
| Withdrawal by Subject | 0 | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: The study was prematurely terminated. No meaningful efficacy analysis could be performed on the data.
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 | Placebo | AM-111 0.4 mg/ml | AM-111 0.8 mg/ml | Total |
|---|---|---|---|---|---|
| Participants analysed | 18 | 19 | 19 | 56 | |
| Age, Customized: Age | years | 57.7 (SD 15.25) | 57.0 (SD 15.13) | 54.6 (SD 14.36) | 55.6 (SD 14.96) |
| Sex: Female, Male: Female | Participants | 12 | 7 | 8 | 27 |
| Sex: Female, Male: Male | Participants | 6 | 12 | 11 | 29 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 12 | 8 | 11 | 31 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 6 | 10 | 6 | 22 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Pure Tone Average (PTA), measured over Day 0 and Day 91: The study was prematurely terminated..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is Pure Tone Average (PTA), assessed as the change in pure tone audiometry between Day 0 before treatment and Day 91. PTA combines hearing-threshold measurements across test tones into a summary measure. In general, such a summary can make the overall pattern of hearing thresholds easier to compare than a list of tone-specific measurements, while still depending on the testing procedures and analysis choices used.
For this trial, the endpoint was intended to measure hearing recovery over the follow-up period. Comparing change across randomized groups would address whether the observed change differed between AM-111 and placebo. The registry record does not give a PTA unit, a statistical parameter, a dispersion measure, or a numerical result. It states that the study was prematurely terminated, not all planned data were collected, and no meaningful efficacy analysis could be performed. Accordingly, there is no reported PTA estimate to interpret as the amount or precision of hearing change.
WRS, or Word Recognition Score, is identified as the main secondary outcome. The registry record does not give its results or measurement details. PTA and WRS address related but distinct aspects of hearing assessment, so an absent PTA analysis cannot be replaced by an assumed WRS result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the registry record does not report a meaningful efficacy analysis. It describes PTA change from Day 0 to Day 91 as the primary outcome, but also states that the trial was prematurely terminated, planned data were not all collected, and analyses were pre-specified not to be completed because of the termination. No treatment-effect estimate, uncertainty interval, or inferential test is reported for PTA. No efficacy results for WRS are reported either.
That means the posted results do not quantify how much hearing changed within any group or whether the change differed among the randomized groups. They also do not show that the groups had identical outcomes. An absent estimate is not an estimate of no effect: it is a lack of an interpretable efficacy comparison in the registry record. The trial's stated objective and randomized design describe what it sought to evaluate, not what the available efficacy results establish.
Enrollment is reported as 56. The safety entries give the number at risk and the number affected for each listed intervention group, but those entries do not supply a completed efficacy analysis or a basis for inferring hearing outcomes. Nor should the safety counts be used to reconstruct unreported efficacy results. The registry status is TERMINATED, while the primary completion date is 2018-02; neither fact, by itself, explains why termination occurred. The reason for termination is not reported in the registry record.
Precision cannot be evaluated for the primary treatment comparison because there is no reported estimate or confidence interval. In general, a confidence interval describes a range of values compatible with an estimate and its statistical uncertainty under the analysis assumptions. Without an estimate and interval, readers cannot judge whether an efficacy comparison was precise, whether it could exclude clinically important differences, or whether uncertainty was wide. Those conclusions cannot be recovered from the enrollment figure alone.
The safety data require similarly careful reading. The registry lists serious adverse event counts for each group, along with counts for other adverse events and deaths. These are descriptive counts, not a complete comparative safety analysis. The record does not report statistical comparisons, adjusted estimates, or uncertainty intervals for these outcomes. Some serious-event terms and percentages are listed, but their denominator and relation to each intervention group are not specified in that listing.
In short, the registry supports a description of the trial's design, intended outcome, termination, and posted safety counts. It does not support a conclusion about the efficacy of AM-111 for hearing recovery, or a precise comparative judgment about safety. The limitation is not merely that an effect estimate is small or uncertain; no meaningful efficacy estimate is reported at all.
9. Statistical Methods Explained
The registry record identifies the broad design and outcomes, but reports no completed efficacy analyses. The statistical concepts below explain how such a trial question is generally approached; they do not describe unreported methods used in this study.
What does randomization contribute?
In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the outset, including differences that are measured and differences that may not be known. It does not guarantee that groups will be identical, especially in a study with limited enrollment. Comparisons should therefore be based on the actual randomized groups and the analysis plan, not on an assumption that randomization removes all uncertainty.
The record labels allocation RANDOMIZED, but the method for generating the sequence and concealing assignments is not reported in the registry record. The masking designation is QUADRUPLE. The identities of the masked parties and procedures for maintaining masking are not reported in the registry record. These broad labels are informative, but they do not provide enough detail to assess implementation.
How would a change endpoint be compared?
For a change endpoint, a group-level summary of the Day 0 to Day 91 difference could be compared across assigned groups. In general, an analysis might estimate change within each group and then estimate a contrast between groups, with uncertainty around that contrast. The choice of model can affect interpretation and precision, and the analysis should account for the trial's design and the data actually collected. The registry record does not report a statistical model, an analysis parameter, or a numerical PTA result.
PTA is described as change in pure tone audiometry between Day 0 and Day 91. The record does not specify the exact PTA calculation, handling of individual tones, or an analysis population. It lists no unit, dispersion measure, or estimate. Consequently, a reader cannot verify the intended scale or reproduce a group comparison from the registry entry.
What does an uncertainty interval tell a reader?
Generally, a confidence interval places an estimate alongside a range expressing statistical uncertainty under the model and assumptions used. A narrow interval indicates greater precision than a wide interval, but neither width nor location can be assessed without a reported estimate and interval. The registry record reports no confidence interval for the primary efficacy outcome. It also reports no p-value or other inferential result for that outcome.
Even when estimates are available, statistical uncertainty is not the same as clinical importance. A comparison can be statistically uncertain while allowing a range of effects, and an estimate alone does not determine whether a difference matters to patients. In this trial record, the more basic limitation applies: there is no meaningful efficacy estimate to evaluate for magnitude, precision, or clinical interpretation.
What is the role of masking?
As a general principle, masking can reduce the influence of treatment knowledge on participant reports, clinical management, outcome assessment, and decisions about analysis. Its value depends on how masking is implemented and whether it remains credible throughout the study. The QUADRUPLE designation does not, by itself, identify the masked roles or show whether masking was successful. Those details are not reported in the registry record.
Why can incomplete data matter?
When planned observations are missing, the analysis may represent a different subset of participants than intended. The consequences depend on why observations are missing, how much information is absent, and what assumptions the analysis makes about missingness. General statistical approaches can include prespecified handling rules and sensitivity analyses to examine how conclusions change under alternative assumptions. The registry record says not all planned data were collected, but does not describe the missingness pattern, the missing-data method, or any sensitivity analysis.
The primary outcome description states that analyses were pre-specified not to be completed due to premature termination. This is a reported reason that no meaningful efficacy analysis was performed; it does not reveal the detailed analysis plan. The plan's model, covariates, treatment contrasts, significance threshold, confidence-interval method, and any interim analyses are not reported in the registry record.
Why can over-dispersion matter?
Generally, over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than the data contain, uncertainty can be understated and inferential results can appear more decisive than warranted. Model choice should match the outcome type and its variability. No distributional model or over-dispersion assessment is reported in the registry record; this concept is general and does not imply that over-dispersion occurred in this trial.
Likewise, there is no reported sample-size justification or power calculation for the trial. The enrollment figure is not a substitute for a documented design rationale, and the record does not state whether the study was expected to have adequate precision for a particular effect. Any planning illustration based on an observed effect would be distinct from the trial's own design justification, and this record supplies no meaningful efficacy estimate on which to base such an illustration.
Finally, the registry lists two outcome measures and zero analyses. These entries align with the stated absence of meaningful efficacy analysis, but do not establish what analyses were performed outside the registry or whether results were reported elsewhere. No publication or external result is identified in the registry record. Interpretation should remain limited to the information recorded there.
10. Multiplicity, Missing Data and Analysis Populations
PTA is designated as the primary outcome, and WRS is identified as the main secondary outcome. The registry record reports two outcome measures and zero analyses. It does not provide a multiplicity strategy, such as a prespecified ordering of tests or an adjustment to control the chance of false-positive findings across multiple outcomes or comparisons. It also does not report a complete set of outcome-specific results from which multiplicity could be assessed.
The trial includes placebo and AM-111 at 0.4 mg/ml and 0.8 mg/ml, creating more than one possible treatment comparison. Which comparisons were intended to be primary, whether the concentrations were to be compared with each other, and how those comparisons were to be handled are not reported in the registry record. It also does not report an analysis plan or interim-analysis procedures. These omissions do not establish that such plans did not exist; they mean they are not documented in the registry record.
Missing-data information is limited. The primary outcome description says not all planned data were collected, but the record does not identify which observations were missing, why they were missing, or how missingness differed by group or visit. An analysis population, imputation method, and sensitivity analyses are not reported in the registry record. In general, missing-data assumptions matter because the participants with observed follow-up may not represent everyone randomized. Here, the stated premature termination and lack of meaningful efficacy analysis prevent evaluation of the primary comparison regardless of which method might otherwise have been planned.
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 |
|---|---|---|---|
| Placebo | 1 | 18 | 5.6% |
| AM-111 0.4 mg/ml | 1 | 19 | 5.3% |
| AM-111 0.8 mg/ml | 0 | 19 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 0 of 18 |
| AM-111 0.4 mg/ml | 0 of 19 |
| AM-111 0.8 mg/ml | 0 of 19 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 8 of 18 |
| AM-111 0.4 mg/ml | 11 of 19 |
| AM-111 0.8 mg/ml | 10 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | AM-111 0.4 mg/ml | AM-111 0.8 mg/ml |
|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | 1 of 18 | 0 of 19 | 0 of 19 |
| Chest pain | General disorders | 1 of 18 | 0 of 19 | 0 of 19 |
| Sepsis | Infections and infestations | 0 of 18 | 1 of 19 | 0 of 19 |
| Acute kidney injury | Renal and urinary disorders | 0 of 18 | 1 of 19 | 0 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | AM-111 0.4 mg/ml | AM-111 0.8 mg/ml |
|---|---|---|---|---|
| Dizziness | Nervous system disorders | 2 of 18 | 2 of 19 | 1 of 19 |
| Headache | Nervous system disorders | 1 of 18 | 1 of 19 | 3 of 19 |
| Tinnitus | Ear and labyrinth disorders | 1 of 18 | 2 of 19 | 1 of 19 |
| Dyspesia | Nervous system disorders | 2 of 18 | 0 of 19 | 1 of 19 |
| Nausea | Gastrointestinal disorders | 2 of 18 | 1 of 19 | 0 of 19 |
| Asthenia | General disorders | 2 of 18 | 1 of 19 | 0 of 19 |
| Pruritus | Skin and subcutaneous tissue disorders | 1 of 18 | 1 of 19 | 1 of 19 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 1 of 18 | 1 of 19 | 1 of 19 |
| Dyspesia | Gastrointestinal disorders | 2 of 18 | 0 of 19 | 1 of 19 |
| Vertigo positional | Ear and labyrinth disorders | 1 of 18 | 0 of 19 | 1 of 19 |
Serious events with the highest arm-level rate: vertigo (5.6%), chest pain (5.6%), sepsis (5.3%), acute kidney injury (5.3%).
The registry lists serious adverse events, other adverse events, and deaths separately for placebo and each AM-111 concentration. For serious adverse events, the listed at-risk and affected counts are 18 and 1 for placebo, 19 and 1 for AM-111 0.4 mg/ml, and 19 and 0 for AM-111 0.8 mg/ml. The listed death count is 0 in each group.
For other adverse events, the at-risk and affected counts are 18 and 8 for placebo, 19 and 11 for AM-111 0.4 mg/ml, and 19 and 10 for AM-111 0.8 mg/ml. These are descriptive counts in the registry record. They are not adjusted comparisons and do not include reported uncertainty intervals or statistical tests, so they should not be read as establishing a difference between interventions.
The registry also lists Vertigo (5.6%), Chest pain (5.6%), Sepsis (5.3%), and Acute kidney injury (5.3%) among the top serious terms. The denominator and group-specific context for these percentages are not reported in the registry record. The entries therefore do not show, on their own, how often each term occurred in each intervention group. Safety counts provide useful recorded information, but the incomplete trial and lack of comparative analysis limit what can be concluded from them.
12. What the Result Does, and Does Not, Mean
The result means that the registered trial did not yield a meaningful efficacy analysis of AM-111 for its primary hearing outcome. Although PTA change from Day 0 to Day 91 was the stated primary endpoint, the registry record says the study was prematurely terminated, planned data were not all collected, and the prespecified analyses were not completed. No estimate of hearing recovery or between-group difference is reported.
That does not mean the trial demonstrated no effect, and it does not mean the treatment groups had the same outcomes. Both would require evidence from a completed, interpretable comparison. The absent analysis leaves the efficacy question unresolved in this registry record. It also prevents assessment of the size and precision of any possible difference.
The record does document a randomized, quadruple-masked, parallel-group design, enrollment of 56, the planned interventions, and selected safety counts. These registry entries describe the study structure and the information recorded, but they do not replace an efficacy result. The safety entries should likewise be read as descriptive counts rather than definitive comparative evidence.
The termination status alone does not explain why the study ended, whether a safety concern prompted the decision, or whether operational considerations were involved. The reason for termination is not reported in the registry record. The record also does not report a sample-size justification, detailed analysis plan, or missing-data approach, so those aspects cannot be used to explain the lack of an efficacy estimate.
The appropriate statistical conclusion is narrow: the registry record does not provide a usable estimate for the primary question. It neither confirms nor rules out benefit, and it does not establish comparative safety. Any broader conclusion would go beyond the posted results.
13. Why This Trial Matters Statistically
This trial illustrates why design labels and efficacy evidence must be distinguished. Randomization and masking describe safeguards that can strengthen a comparison, but they cannot produce an interpretable treatment-effect estimate when the planned data are incomplete and the efficacy analysis is not performed. A well-described question is not the same as an answered question.
It also shows why a registry's outcome status matters. PTA was specified as the primary outcome and WRS as the main secondary outcome, yet the record reports zero analyses and explicitly says that no meaningful efficacy analysis could be performed. Without estimates and their uncertainty, readers cannot evaluate effect size, precision, or whether results would support a clinically important difference.
The entry is also a reminder that termination should not be treated as an outcome. The status is TERMINATED, but the reason for termination is not reported in the registry record. Statistical interpretation should not assign a cause or infer a result from that status alone.
Finally, descriptive safety counts and an efficacy comparison answer different questions. Safety counts can convey what was recorded among participants at risk, but without comparative analyses they do not establish a treatment-related difference. This distinction is particularly important when the efficacy outcome was not meaningfully analyzed. The trial record therefore has value for understanding the intended design and the limits of the available evidence, even though it does not resolve the stated efficacy question.
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 limitation is explicit: the study was prematurely terminated, not all planned data were collected, and no meaningful efficacy analysis could be performed. The record also says analyses were pre-specified not to be completed after premature termination. As a result, there is no reported estimate for PTA change from Day 0 to Day 91 and no reported comparative efficacy result for WRS.
The registry does not explain the reason for termination. It does not report participant-level outcome completeness, the pattern or reasons for missing measurements, or any method for handling missing data. The analysis population is not reported in the registry record, and no sensitivity analyses are described. These gaps prevent assessment of how incomplete follow-up might have affected an efficacy comparison.
Statistical details are also limited: the record provides no model, treatment contrast, estimate, confidence interval, p-value, or sample-size justification. The allocation method, masking procedures, and interim-analysis plan are not reported in the registry record. The intended handling of multiple outcomes and treatment comparisons is also not reported.
The safety information is descriptive. Although group counts are listed, the record does not report comparative estimates or uncertainty intervals. The context and denominators for the listed serious-event term percentages are not reported. These limitations constrain both efficacy and safety interpretation and should not be filled by assumptions about the protocol or reasons for the study's termination.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of AM-111 as Acute Sudden Sensorineural Hearing Loss Treatment — NCT02809118.
- Registry record last updated 2020-08-07; status last verified 2020-06.
- Results first posted 2020-08-07.
- 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
NCT02809118, titled Efficacy and Safety of AM-111 as Acute Sudden Sensorineural Hearing Loss Treatment, is a phase 3 randomized, quadruple-masked, parallel-group trial sponsored by Auris Medical, Inc. It evaluated intratympanic AM-111 at 0.4 mg/ml and 0.8 mg/ml against placebo gel. Enrollment was 56. The registered start was 2016-06, primary completion was 2018-02, and the status is TERMINATED.
The primary endpoint was PTA change between Day 0 and Day 91; WRS was the main secondary outcome. The registry states that the trial was prematurely terminated, not all planned data were collected, and no meaningful efficacy analysis could be performed. It reports selected adverse-event counts, but no comparative efficacy estimate or completed statistical analysis. The reason for termination, detailed analysis plan, missing-data methods, and sample-size justification are not reported in the registry record.