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 AM-101 in the Treatment of Post-Acute Tinnitus 1 (NCT01934010), a na phase 3 study. The primary outcome is Frequency of Subjects With a Deterioration of Hearing Threshold at Day 35 (Air Conduction).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01934010 |
| Phase | Phase 3 |
| Condition | Tinnitus |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 260 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Auris Medical, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People with tinnitus enrolled in the post-acute treatment extension. For the primary endpoint, the safety analysis set includes subjects who had at least one intratympanic injection; a subject is considered at a time point only when a hearing-threshold measurement is available.
Intervention
AM-101 gel delivered by intratympanic injection. The study purpose is to test the safety and local tolerance of repeated treatment cycles.
Comparator
There is no comparator group described. The registry identifies a single-group, open-label extension, not a randomized comparison.
Primary question
How many subjects had deterioration in air-conduction hearing threshold from Day 1 (TV1) to Day 35 (FUV2) of cycle 1, defined as worsening by at least 15 dB in two neighboring sound frequencies?
The clinical question is primarily about safety and local tolerance during repeated treatment cycles, rather than a comparative treatment effect. The primary outcome records a hearing-threshold change meeting a specified definition. It is not a general measure of tinnitus symptoms, and the registry record does not identify it as an efficacy outcome.
The study title describes post-acute peripheral tinnitus and identifies the study as an open-label extension to TACTT2. The record does not report further eligibility criteria or explain how participants entered the extension. It also does not specify a control condition, placebo, or alternative treatment for comparison.
Although the question concerns AM-101 exposure, the primary endpoint is assessed during cycle 1, while the study purpose also refers to repeated cycles. The registry lists secondary hearing-threshold outcomes at Day 84, Day 168, and Day 252. Those later assessments extend the safety observation period, but they do not create a control group. Without a comparator, any observed changes can be described for the participants assessed, but cannot be separated from changes that might have occurred over time or for other reasons.
3. Trial Design
This is a Phase 3, completed, single-group study of AM-101, titled as an open-label extension to the TACTT2 study. The registry lists an enrollment of 260 and identifies Auris Medical, Inc. as sponsor. The recorded start is 2014-06, and primary completion is 2017-01.
The study is open-label, with masking listed as none and allocation listed as not applicable. These design features mean the record does not describe randomized assignment or blinding. It identifies one intervention, AM-101, described as gel for intratympanic injection. The study purpose is to test safety and local tolerance with repeated treatment cycles.
The adverse-event results are presented in groups titled 1 Cycle AM-101, 2 Cycles AM-101, and 3 Cycles AM-101. The record does not explain how participants came to receive those cycle counts, whether the groups are mutually exclusive, or how participation in the extension relates to the parent study. They should not be interpreted as randomized treatment arms or as like-for-like control groups.
The primary endpoint covers Day 1 (TV1) to Day 35 (FUV2) of cycle 1. The registry also lists hearing-threshold outcomes at Day 84, Day 168, and Day 252. It does not report the detailed visit schedule, injection schedule, treatment-cycle duration beyond the stated outcome timeframes, or other protocol procedures. The registry record also does not report the rationale for the enrollment target or the study’s original sample-size justification.
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: Main Inclusion Criteria: * completion of TACTT2 study * negative pregnancy test (women of childbearing potential) * willing and able to attend the study visits during at least one treatment cycle.
Overall Study
| Stage | 1 Cycle AM-101 | 2 Cycles AM-101 | 3 Cycles AM-101 |
|---|---|---|---|
| STARTED | 114 | 67 | 76 |
| COMPLETED | 91 | 56 | 74 |
| NOT COMPLETED | 23 | 11 | 2 |
Reasons for not completing this period:
| Reason | 1 Cycle AM-101 | 2 Cycles AM-101 | 3 Cycles AM-101 |
|---|---|---|---|
| Adverse Event | 1 | 1 | 0 |
| Withdrawal by Subject | 15 | 6 | 2 |
| Lost to Follow-up | 7 | 4 | 0 |
Analysis population for the primary outcome, as defined in the registry: The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | 1 Cycle AM-101 | 2 Cycles AM-101 | 3 Cycles AM-101 | Total |
|---|---|---|---|---|---|
| Participants analysed | 114 | 67 | 76 | 257 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 106 | 61 | 64 | 231 |
| Age, Categorical: >=65 years | Participants | 8 | 6 | 12 | 26 |
| Age, Continuous | years | 43.1 (SD 14.1) | 44.7 (SD 13.9) | 47.6 (SD 15.5) | 44.8 (SD 14.5) |
| Sex: Female, Male: Female | Participants | 25 | 17 | 21 | 63 |
| Sex: Female, Male: Male | Participants | 89 | 50 | 55 | 194 |
| Region of Enrollment: United States | participants | 71 | 45 | 40 | 156 |
| Region of Enrollment: Czechia | participants | 24 | 7 | 22 | 53 |
| Region of Enrollment: Canada | participants | 4 | 11 | 9 | 24 |
| Region of Enrollment: Israel | participants | 1 | 1 | 1 | 3 |
| Region of Enrollment: South Korea | participants | 11 | 1 | 4 | 16 |
| Region of Enrollment: Turkey | participants | 3 | 2 | 0 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Frequency of Subjects With a Deterioration of Hearing Threshold at Day 35 (Air Conduction), measured over Day 1 (TV1) to Day 35 (FUV2) of cycle 1.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Number subject affected |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of subjects with deterioration in air-conduction hearing threshold between Day 1 (TV1) and Day 35 (FUV2) of cycle 1. Air conduction describes sound reaching the inner ear through the external auditory canal and middle-ear structures. Hearing threshold is the lowest sound pressure at which a sound can be perceived.
An event is defined as worsening of at least 15 dB in two neighboring sound frequencies. This definition makes the endpoint a threshold-based safety measure: it counts subjects whose measured change meets the stated criterion. It does not describe the size of every subject’s change, nor does it measure tinnitus severity.
The endpoint is useful for monitoring a possible change in hearing during treatment because it applies a stated measurement rule to audiometric results. Its interpretation depends on the availability of threshold measurements. The safety analysis set includes subjects with at least one intratympanic injection, and a subject is included at a time point only if the hearing threshold is available.
The registry record identifies the endpoint and its definition but does not report the number of subjects who met that definition. It therefore does not permit a direct reading of the observed primary outcome or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a single-group, open-label extension intended to assess safety and local tolerance. Its primary endpoint is a defined deterioration in air-conduction hearing threshold by Day 35 of cycle 1. However, the number of subjects meeting the endpoint is not reported in the registry record. Neither an estimate of the primary outcome nor an uncertainty interval is available in the posted results described by the record. The primary safety finding therefore cannot be characterized from this record.
The adverse-event information includes group-specific counts. In the 1 Cycle AM-101 group, 114 subjects were at risk for serious adverse events and 2 were affected; 114 were at risk for other adverse events and 25 were affected. In the 2 Cycles AM-101 group, the corresponding counts were 67 at risk and 1 affected for serious events, and 67 at risk and 25 affected for other events. In the 3 Cycles AM-101 group, the counts were 76 at risk and 1 affected for serious events, and 76 at risk and 37 affected for other events. These are counts, not evidence from a randomized comparison. The record does not establish that the cycle groups are comparable or explain how participants came to be represented in them.
The registry also lists serious-event terms with percentages: Adnexa uteri cyst, 1.5%; Adnexa uteri mass, 1.5%; Osteonecrosis, 1.3%; Liver function test increased, 0.9%; and Lip and/or oral cavity cancer, 0.9%. The record does not specify the denominator for these percentages in the listed information. These terms should be read as reported adverse-event categories, not as evidence that AM-101 caused the events. Death counts are not reported in the registry record.
Because the primary endpoint result is absent and the study has no described comparator, the record cannot establish how the observed hearing-threshold changes compare with an untreated or alternatively treated group. It also cannot show whether an event count differs from what would have occurred without treatment. The counts and event terms describe reported safety information, but they do not support a causal conclusion or a comparative estimate.
9. Statistical Methods Explained
What kind of outcome is the primary endpoint?
The primary outcome is a count of subjects who meet a defined event criterion. Each subject is assessed for whether the hearing-threshold change meets the rule: worsening by at least 15 dB in two neighboring sound frequencies between the specified visits. This is different from analyzing the average change in hearing threshold. A count gives the number meeting the event definition, while interpretation of that count ordinarily also depends on how many subjects were assessed.
General statistical explanation: for an event count in a defined group, the denominator matters because the same count can have different meanings in groups of different sizes. The registry does identify the safety analysis set and says a subject is considered at a time point only if a threshold is available. It does not report the primary event count or the number with an available threshold at that assessment, so an event proportion cannot be read from the record.
What does the single-group design allow?
The registry identifies a single-group, open-label study and gives no comparator. An outcome can be described among assessed participants, but there is no randomized control group against which to estimate a treatment contrast. The adverse-event groups categorized by 1, 2, or 3 cycles are not identified as randomized arms. Their observed counts should not be treated as a comparison of assigned treatment strategies.
General statistical explanation: a comparative treatment effect requires a defined contrast between groups and an analysis that supports that contrast. Randomization can help make groups comparable at the start of a study, but this record does not describe randomized allocation. Differences among cycle-count groups could reflect differences in who received or continued treatment, among other factors. The registry does not report enough detail to assess such factors.
What can uncertainty estimates tell a reader?
A confidence interval is a statistical interval expressing uncertainty around an estimated quantity under a specified analysis. It helps show how much precision the observed information supports; it does not guarantee that the true value lies within the interval. No confidence interval for the primary endpoint is reported in the registry record. The record also does not give a primary endpoint count from which a reader could evaluate the magnitude or precision of that outcome.
The registry does not report a statistical test or p-value for the primary endpoint in the information described. Without an estimate and its uncertainty, the clinical and statistical significance of the primary endpoint cannot be judged. This is not evidence that the outcome was zero or that no analysis was conducted; the result is simply not reported in the registry record.
How should the adverse-event counts be read?
The adverse-event entries distinguish subjects at risk from subjects affected, and separately list serious and other adverse events. The figures are counts within the three cycle-labeled groups. They are descriptive safety information. The registry does not state that these groups are independent, randomized, or intended for a formal comparison. No rate should be inferred without clear denominators and a suitable analysis, and no causal relationship should be inferred from an event being listed.
General statistical explanation: serious adverse events and other adverse events are categories that describe event reporting and severity status; they are not interchangeable with the primary hearing-threshold endpoint. A participant may also experience more than one event, and an event term is not automatically equivalent to a unique affected participant. The registry information does not explain event counting conventions in enough detail to reconstruct subject-level event histories.
What do the planning illustrations represent?
The registry record does not report the trial’s own sample-size justification. Planning illustrations based on the observed effect are not the trial’s original design rationale and are not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. Those are hypothetical planning conditions. They do not change the actual study design, which is listed as single-group and not a randomized comparison.
General statistical explanation: a sample-size calculation describes how many participants a hypothetical design may require under specified assumptions. Its result depends on the assumed effect and analysis model. It is not a measure of the probability that a completed trial has detected an effect, and it cannot replace a reported estimate with uncertainty. The record does not give details of a prospective calculation for this study.
Which analysis choices remain unclear?
The record lists six outcome measures and eight analyses, but the detailed analysis methods are not reported in the registry record. This includes whether the primary endpoint was analyzed with a particular inferential procedure, how any covariates were handled, and whether the analysis included sensitivity checks. The primary analysis population is described as the safety analysis set, but further analysis details are not stated. As a result, the endpoint definition can be understood, while the precise statistical procedure and its uncertainty cannot be reconstructed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures and eight analyses. The primary outcome is hearing-threshold deterioration at Day 35, and secondary hearing-threshold outcomes are listed at Day 84, Day 168, and Day 252. The record does not report whether a formal hierarchy was used to interpret these outcomes or whether any adjustment for multiple testing was planned or applied.
General statistical explanation: when several outcomes or analyses are examined, the chance of at least one apparently unusual result can increase if each is assessed separately. Prespecified priorities or multiplicity adjustments can help define how results should be interpreted. Without such information, it is not possible to determine whether the reported analyses were confirmatory, exploratory, or adjusted for the number of questions considered.
The primary endpoint definition specifies the safety analysis set: subjects with at least one intratympanic injection. It further states that subjects are considered at a time point only when the hearing threshold is available. The registry does not report how many measurements were missing, why they were unavailable, or whether any imputation or sensitivity analysis was used. It also does not report how withdrawals or incomplete follow-up were handled for the later assessments.
The registry record does not report interim analyses, stopping rules, or a missing-data analysis plan. Those details should not be inferred from the completed status or from the presence of later outcome timepoints. The absence of these details limits assessment of how the outcomes were selected and how missing measurements may have affected interpretation.
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 |
|---|---|---|---|
| 1 Cycle AM-101 | 2 | 114 | 1.8% |
| 2 Cycles AM-101 | 1 | 67 | 1.5% |
| 3 Cycles AM-101 | 1 | 76 | 1.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 1 Cycle AM-101 | 25 of 114 |
| 2 Cycles AM-101 | 25 of 67 |
| 3 Cycles AM-101 | 37 of 76 |
Most frequent serious adverse event terms
| Event term | Organ system | 1 Cycle AM-101 | 2 Cycles AM-101 | 3 Cycles AM-101 |
|---|---|---|---|---|
| Liver function test increased | Investigations | 1 of 114 | 0 of 67 | 0 of 76 |
| Lip and/or oral cavity cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 114 | 0 of 67 | 0 of 76 |
| Adnexa uteri cyst | Reproductive system and breast disorders | 0 of 114 | 1 of 67 | 0 of 76 |
| Adnexa uteri mass | Reproductive system and breast disorders | 0 of 114 | 1 of 67 | 0 of 76 |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | 0 of 114 | 0 of 67 | 1 of 76 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 1 Cycle AM-101 | 2 Cycles AM-101 | 3 Cycles AM-101 |
|---|---|---|---|---|
| Ear pain | Ear and labyrinth disorders | 10 of 114 | 13 of 67 | 8 of 76 |
| Headache | Nervous system disorders | 5 of 114 | 7 of 67 | 9 of 76 |
| Ear discomfort | Ear and labyrinth disorders | 3 of 114 | 9 of 67 | 7 of 76 |
| Hypoacusis | Ear and labyrinth disorders | 5 of 114 | 4 of 67 | 4 of 76 |
| Nasopharyngitis | Infections and infestations | 4 of 114 | 2 of 67 | 6 of 76 |
| Otorrhoea | Ear and labyrinth disorders | 1 of 114 | 4 of 67 | 3 of 76 |
| Tinnitus | Ear and labyrinth disorders | 0 of 114 | 2 of 67 | 5 of 76 |
| Anxiety | Psychiatric disorders | 1 of 114 | 1 of 67 | 2 of 76 |
| Tympanic membrane perforation | Ear and labyrinth disorders | 0 of 114 | 0 of 67 | 3 of 76 |
| Vertigo | Ear and labyrinth disorders | 0 of 114 | 2 of 67 | 1 of 76 |
Serious events with the highest arm-level rate: adnexa uteri cyst (1.5%), adnexa uteri mass (1.5%), osteonecrosis (1.3%), liver function test increased (0.9%), lip and/or oral cavity cancer (0.9%).
For serious adverse events, the registry lists the number at risk and the number affected separately for each cycle-labeled group. The 1 Cycle AM-101 group has 114 at risk and 2 affected; the 2 Cycles AM-101 group has 67 at risk and 1 affected; and the 3 Cycles AM-101 group has 76 at risk and 1 affected. These are the reported counts, not a randomized comparison.
The record also lists other adverse events: 25 affected among 114 at risk in the 1 Cycle AM-101 group, 25 among 67 in the 2 Cycles AM-101 group, and 37 among 76 in the 3 Cycles AM-101 group. These entries should be kept distinct from the serious-event counts. The record does not explain whether the cycle groups overlap, how exposure duration varied, or how event episodes were counted.
Several serious-event terms are listed with percentages, including Adnexa uteri cyst at 1.5% and Adnexa uteri mass at 1.5%. The denominator and event-counting details for these percentages are not reported in the registry record. The listed terms do not establish that treatment caused the events. Death counts are not reported in the registry record; that absence should not be read as confirmation that no deaths occurred.
12. What the Result Does, and Does Not, Mean
The registry record establishes that AM-101 was studied in a completed Phase 3, open-label extension with a single-group design and a stated enrollment of 260. It describes an intended safety and local-tolerance assessment involving repeated treatment cycles. It also defines a primary hearing-threshold endpoint and lists later hearing-threshold outcomes, together with adverse-event counts by cycle-labeled group.
What the record does not establish is the observed result for the primary endpoint. The number of subjects meeting the threshold-deterioration definition is not reported in the registry record. There is also no reported estimate or confidence interval for that endpoint in the listed information. Consequently, readers cannot assess the observed frequency or its precision from this record.
The safety counts are descriptive. They show the reported number at risk and affected in each cycle-labeled group, but the record does not identify these groups as randomized or otherwise comparable. It would be inappropriate to interpret differences between them as evidence that receiving more cycles caused a different event burden. The serious-event terms and percentages likewise do not establish causation.
General statistical explanation: a single-group study can document what happened among participants observed, but it cannot by itself distinguish a treatment-related change from natural change, background events, or other influences. A comparator and a clearly reported analysis are needed for a comparative estimate. The record also does not report enough information to assess the influence of missing hearing-threshold measurements.
Thus, the record supports a description of the study’s design, endpoint definition, and selected safety counts. It does not support a conclusion about the primary endpoint’s observed frequency, a causal effect of AM-101, or a comparison with another treatment or no treatment.
13. Why This Trial Matters Statistically
This study is statistically notable because its central outcome is an explicitly defined safety event rather than a continuous average change. The event rule requires a deterioration of at least 15 dB in two neighboring sound frequencies. That makes the outcome interpretable as the number of subjects crossing a clinical measurement threshold, while also making the result dependent on having hearing-threshold measurements at the relevant time point.
The design matters just as much as the endpoint. This is an open-label, single-group extension with no comparator described. The study can document adverse events and threshold changes among observed participants, but it does not provide the randomized contrast needed to attribute differences to AM-101. The groups labeled by cycle count should not be mistaken for control arms.
The registry’s description of the safety analysis set is useful because it states that participants must have had at least one intratympanic injection and that a threshold must be available for inclusion at a time point. At the same time, missingness details and the primary endpoint count are not reported in the registry record. These omissions prevent evaluation of both the observed frequency and the completeness of outcome ascertainment.
The posted serious and other adverse-event counts add descriptive context, but they do not fill the gap in the primary outcome result. They also cannot establish causality or comparative safety without further design and analysis information. The statistical lesson is that a precise endpoint definition is valuable, but interpretation still depends on reported results, denominators, uncertainty, and an appropriate comparison structure.
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 is not reported in the registry record. The endpoint definition and analysis population are described, but the number of subjects meeting the deterioration criterion and the number assessed at that time point are not stated in the listed results. No estimate of precision is reported for the primary outcome.
The study is identified as single-group and open-label, with no comparator. Its cycle-labeled adverse-event groups are not described as randomized arms, and the record does not explain how participants were categorized or whether groups overlap. Therefore, comparisons among those groups would not establish the effect of cycle count.
Although the primary population is identified as the safety analysis set, the record does not report the amount or reasons for missing hearing-threshold data, how missing observations were handled, or whether sensitivity analyses were conducted. It also does not provide detailed methods for the eight listed analyses or say whether multiplicity was addressed.
The serious adverse-event terms are accompanied by percentages, but the denominator and event-counting details are not stated in the registry information. Death counts are not reported. The record does not report the original sample-size justification, interim analyses, or a detailed statistical analysis plan. These are specific gaps in assessing the precision, completeness, and interpretation of the posted results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: AM-101 in the Treatment of Post-Acute Tinnitus 1 — NCT01934010.
- Registry record last updated 2018-05-16; status last verified 2018-04.
- Results first posted 2018-03-09.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01934010 is a completed Phase 3, single-group, open-label extension study of AM-101 gel by intratympanic injection for tinnitus. The registry lists enrollment of 260, a start in 2014-06, and primary completion in 2017-01. Its stated purpose is to assess safety and local tolerance with repeated treatment cycles.
The primary outcome is the number of subjects with air-conduction hearing-threshold deterioration from Day 1 (TV1) to Day 35 (FUV2) of cycle 1, defined as worsening by at least 15 dB in two neighboring frequencies. The primary result is not reported in the registry record. Adverse-event counts are listed for groups receiving 1, 2, or 3 cycles, but these are not described as randomized comparison groups.