OTO-313 in Subjects With Subjective Tinnitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for OTO-313 in Subjects With Subjective Tinnitus (NCT03918109), a randomized phase 1, phase 2 study. The primary outcome is Audiometry - Pure Tone Average Done Over 1000, 2000 and 4000 Hertz (HZ).

2. Clinical Question

3. Trial Design

The registry describes a randomized, triple-masked, parallel-group Phase 1/2 study comparing OTO-313 with placebo in people with subjective tinnitus. The official title specifies a single intratympanic injection. Its stated purpose includes evaluating safety, tolerability, plasma pharmacokinetics, and exploratory efficacy. The record lists Otonomy, Inc. as sponsor and reports an overall enrollment of 43 participants.

The registry reports two study parts, with separate OTO-313 and placebo arms in each. For the primary audiometry outcome, Part A results include 6 participants in the OTO-313 arm and 2 in the placebo arm. Part B results include 14 and 15 participants, respectively. These outcome counts are not interchangeable with overall enrollment or the safety populations. The registry does not explain the distinction between the parts or why their outcome sample sizes differ.

The reported study start date is 2019-04-04, and the primary completion date is 2020-05-29. The study status is completed. The primary outcome timeframe is described as up to the end of study: baseline to Day 29, 4 weeks after dosing, for Part A, or baseline to Day 57, 8 weeks after dosing, for Part B.

Further details about the protocol, including eligibility criteria, dose levels, allocation procedures, and the statistical analysis plan, are not reported in the registry record. The design labels establish the broad comparison structure, but do not by themselves specify how the analyses were conducted or how participants were assigned to each study part.

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: Part A and Part B were conducted as 2 separate studies under a single protocol.

Overall Study

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 Audiometry - Pure Tone Average Done Over 1000, 2000 and 4000 Hertz (HZ), measured over Up to end of study (Part A - Day 29 [4 weeks after dosing]), (Part B - Day 57 [8 weeks after dosing]).

The primary outcome is the mean change from baseline in pure tone average hearing thresholds, measured in decibels across 1000, 2000 and 4000 Hertz. Pure tone audiometry measures hearing thresholds at specified sound frequencies. Combining the listed frequencies into an average gives a summary measure of hearing threshold across those tones.

The registry defines a negative change as improvement. The outcome is measured from baseline to Day 29, 4 weeks after dosing, in Part A, and from baseline to Day 57, 8 weeks after dosing, in Part B. The reported group means are -0.3 decibels for Part A OTO-313 and 0.71 decibels for Part A placebo; for Part B, they are -0.8 decibels and 0.3 decibels, respectively. The associated standard deviations are 2.66, 2.5, 6.44 and 6.95, in that same order.

Audiometry is relevant to hearing-threshold changes, but it does not directly quantify the subjective experience of tinnitus. The registry also describes efficacy as exploratory. The posted primary measure should therefore be read as a hearing outcome within a study whose stated purpose included safety, tolerability, pharmacokinetics and exploratory efficacy. The registry record does not report a primary-outcome population description beyond the arm-level results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant contributes a hearing-threshold change measured in decibels, and the registry summarizes each arm using a mean and standard deviation. A mean describes the central level of the observed measurements. A standard deviation describes their spread around that mean. Neither quantity alone describes the uncertainty in a treatment contrast.

The four reported primary-outcome summaries are separated by study part and randomized arm. In Part A, the OTO-313 mean change is -0.3 decibels, with a standard deviation of 2.66 and 6 participants; the placebo mean is 0.71 decibels, with a standard deviation of 2.5 and 2 participants. In Part B, the OTO-313 mean is -0.8 decibels, with a standard deviation of 6.44 and 14 participants; the placebo mean is 0.3 decibels, with a standard deviation of 6.95 and 15 participants. The registry defines negative change as improvement. These summaries should be interpreted within their own study part and follow-up time.

In general, an inferential comparison of two means estimates a contrast between groups and quantifies how uncertain that estimate is. A confidence interval is one way to express uncertainty: it gives a range of values compatible with the data under the statistical method and its assumptions. A p-value is another summary used in hypothesis testing. Neither a confidence interval nor a p-value for this endpoint is reported in the registry record. The arm means and standard deviations do not supply either one, and they do not establish that an observed difference is statistically distinguishable from chance variation.

The record indicates that a two-arm comparison for this continuous endpoint is missing or not estimable. It also reports no analysis results. Consequently, the available registry results support descriptive reading of the separate arms, but not a claim based on a sponsor-reported inferential comparison. There is no reported adjusted effect estimate, standard error, confidence interval, or p-value to interpret. The statistical method intended for the primary comparison is not reported in the registry record.

In general, the standard deviation and the standard error answer different questions. The standard deviation describes variation among participant measurements; the standard error describes the precision of an estimated quantity, such as a mean or contrast. A confidence interval for a mean difference would depend on the analysis method and the data, not only on the displayed means. The registry does not post enough inferential information to reconstruct the sponsor’s analysis. No recalculated estimate should be substituted for a missing sponsor analysis.

In general, over-dispersion means that observed variability is greater than a chosen statistical model expects. When a model does not accommodate the actual variation, uncertainty estimates can be too small or otherwise poorly calibrated. That concept is relevant to statistical interpretation of variable clinical outcomes, but the registry does not report an over-dispersion assessment or a model for this endpoint. The posted standard deviations describe the observed spread; they do not establish that over-dispersion was present.

The registry includes planning assumptions for sample-size illustrations: 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. Those assumptions describe planning illustrations, not observed power and not necessarily the original trial design. The sample-size justification for the trial itself is not reported in the registry record. Planning illustrations cannot show what the study was designed to detect unless the relevant design assumptions are known, and they do not change the interpretation of the observed outcome summaries.

For a continuous outcome, the stated illustration framework concerns participants per arm. In general, a planning calculation estimates how many participants might be needed to detect a specified effect under stated assumptions. It is not a measure of the probability that a completed study’s result is true, nor does it remedy the absence of an inferential result. No additional numerical sample-size result is reported in the registry record for interpretation.

The registry identifies the study as randomized, triple-masked, and parallel. In general, randomization is intended to support comparable treatment groups on average, masking can reduce some forms of bias, and a parallel design assigns participants to a group followed over time rather than having every participant receive each intervention. These general design concepts do not reveal how allocation or masking was implemented in this trial. Those procedural details are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Part A OTO-313", "Part A Placebo", "Part B OTO-313", "Part B Placebo")
n   <- c(6, 2, 14, 15)
m   <- c(-0.3, 0.71, -0.8, 0.3)
sp  <- c(2.66, 2.5, 6.44, 6.95)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Part A OTO-313  6  -0.300  2.660  -3.091  2.491
CARM  Part A Placebo  2  0.710  2.500  -21.752  23.172
CARM  Part B OTO-313  14  -0.800  6.440  -4.518  2.918
CARM  Part B Placebo  15  0.300  6.950  -3.549  4.149

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures and reports no posted secondary outcome results. The primary outcome is the audiometry measure described as mean change from baseline in pure tone average hearing thresholds. The record does not identify a multiplicity adjustment, a hierarchy of hypotheses, or a prespecified strategy for controlling false-positive findings across outcomes or analyses. Those details are not reported in the registry record.

In general, multiplicity arises when several statistical hypotheses are tested. The more tests conducted, the more opportunities there may be for a chance finding to appear noteworthy. Researchers may address this through prespecified testing strategies or statistical adjustments, but the registry does not report such a plan for this study. No claim about the presence or absence of an adjustment can be made from the posted arm summaries.

Missing-data methods and the handling of incomplete outcome measurements are also not reported in the registry record. The primary endpoint counts are 6 and 2 for the Part A OTO-313 and placebo arms, and 14 and 15 for the Part B arms. Safety counts differ: 6 and 2 in Part A, and 17 and 18 in Part B. The record does not explain why the safety and primary-outcome populations differ, or whether missing measurements, exclusions, or other analysis rules account for that difference.

The analysis populations are not described in sufficient detail to identify whether the primary endpoint used an intention-to-treat, per-protocol, or other population. The registry reports no analysis results for the primary comparison and no secondary outcome results. Without a stated population definition, missing-data approach, and analysis plan, the scope of the reported outcome summaries cannot be extended beyond the arm-level counts and values posted in the record.

12. 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: stress cardiomyopathy (5.9%).

The safety results report serious adverse events by study part and arm. In Part A, 0 of 6 participants in the OTO-313 group and 0 of 2 in the placebo group had a serious adverse event. In Part B, 1 of 17 participants in the OTO-313 group and 0 of 18 in the placebo group had a serious adverse event. No deaths are reported in any of the four safety groups.

The registry lists Stress Cardiomyopathy at 5.9% among the top serious adverse-event terms. It does not identify an arm for that term in the posted list, so the term should not be assigned to a particular group based on this record alone. The registry also reports other adverse events affecting 2 of 6 and 1 of 2 participants in Part A, and 5 of 17 and 8 of 18 in Part B, in OTO-313 and placebo arms respectively.

These counts are descriptive. They do not establish whether an event was caused by treatment, and the registry record does not report an inferential comparison of serious adverse events. Small group counts mean that each participant represents a substantial part of the observed group experience. The safety findings should be read as the events posted for these groups, not as a precise estimate of comparative risk.

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

The registry reports descriptive mean changes in pure tone average hearing thresholds, with negative values defined as improvement. The values are -0.3 decibels for Part A OTO-313, 0.71 decibels for Part A placebo, -0.8 decibels for Part B OTO-313, and 0.3 decibels for Part B placebo. The results are reported at different follow-up times: Day 29 for Part A and Day 57 for Part B. They should not be combined as if they arose from one shared time point or one common group comparison.

These measurements concern audiometric hearing thresholds. They do not directly measure the subjective experience of tinnitus, and the record describes efficacy as exploratory. A change in hearing threshold should therefore not be interpreted as a direct measure of change in tinnitus symptoms. The registry’s stated study purpose also includes safety, tolerability, and plasma pharmacokinetics.

The posted group means do not establish a treatment effect. The registry does not report a two-arm inferential comparison, confidence interval, or p-value for the primary outcome. The standard deviations indicate variability in the observed values, but cannot substitute for an uncertainty interval around a treatment contrast. In particular, the small Part A outcome groups warrant caution when interpreting the descriptive means.

Nor do the posted results establish that there was no effect. The absence of a reported inferential comparison is not evidence that the groups were equivalent. The record does not report an equivalence or non-inferiority analysis, nor does it provide a margin for such a question. The results support a limited description of the observed arm-level measurements and safety counts, not a conclusion about treatment benefit, lack of benefit, or the cause of adverse events.

The distinction between endpoint and safety sample sizes also matters. The primary outcome includes 14 and 15 participants in Part B, while the safety counts are 17 and 18. The registry does not explain this difference. Readers should not assume that all participants contributed to each outcome or that the same analysis population was used throughout.

14. Why This Trial Matters Statistically

This trial is statistically informative in part because it illustrates the difference between an outcome summary and a treatment-effect analysis. The registry reports group means, standard deviations, and participant counts for a continuous audiometry endpoint. Those summaries describe the observed arms, but a treatment-effect interpretation ordinarily also requires a defined comparison and information about its uncertainty. That inferential comparison is not reported for the primary outcome.

The separate Part A and Part B results also matter. Part A has 6 OTO-313 participants and 2 placebo participants for the primary endpoint, while Part B has 14 and 15. The parts have different follow-up times, Day 29 and Day 57. Keeping them distinct avoids implying a common follow-up or a combined analysis that the registry does not report. The overall enrollment of 43 does not replace the endpoint-specific counts.

The record offers a concrete reason to distinguish outcome types. Pure tone average hearing thresholds summarize audiometric performance, while subjective tinnitus is the condition under study. A hearing-threshold result should not be treated as a direct measurement of tinnitus experience. This distinction is important when considering what a particular endpoint can and cannot answer.

Finally, the record shows why missing methodological detail limits interpretation. The analysis population, missing-data handling, multiplicity strategy, and statistical analysis plan are not reported. These are not minor labels: they help define which participants and outcomes inform a result and how uncertainty is assessed. Without them, the posted findings remain descriptive and should not be expanded into a stronger statistical conclusion than the registry supports.

15. 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 limitations restrict what can be inferred from the registry record. First, the primary endpoint results are presented as arm-level means and standard deviations, but no two-arm comparison is reported. Confidence intervals and p-values for the primary comparison are also not reported. The direction and precision of a treatment contrast therefore cannot be evaluated from the registry results.

Second, the primary-outcome sample sizes are small, particularly in Part A, where the placebo arm includes 2 participants. The registry does not explain the differences among the primary outcome counts, the safety counts, and total enrollment. Reasons for these differences, including any missing measurements or analysis exclusions, are not reported in the registry record.

Third, Part A and Part B have different endpoint follow-up times. The record does not report details about the parts that would support treating them as directly comparable or combining their results. The separate means should be read within their stated study part and timeframe.

Fourth, the registry does not report the analysis population, missing-data method, multiplicity strategy, or statistical analysis plan. It also does not report the trial’s sample-size justification. The available sample-size assumptions concern planning illustrations and do not establish the original design rationale or observed power.

Finally, the primary outcome is an audiometric hearing-threshold measure, whereas the study concerns subjective tinnitus and describes efficacy as exploratory. The record does not report secondary outcome results that could add further context about tinnitus symptoms. These limitations mean that the posted values are best understood as descriptive registry results, rather than a complete inferential account of the trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: OTO-313 in Subjects With Subjective Tinnitus — NCT03918109.
• Registry record last updated 2022-12-23; status last verified 2022-12.
• Results first posted 2022-12-23.
• 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.

19. Record Summary

The completed study, NCT03918109, evaluated OTO-313 in subjects with subjective tinnitus. The registry describes a randomized, triple-masked, parallel Phase 1/2 study with placebo as comparator and an overall enrollment of 43. The official title specifies a single intratympanic injection. The stated study purpose includes safety, tolerability, plasma pharmacokinetics, and exploratory efficacy.

The primary outcome is mean change from baseline in pure tone average hearing thresholds across 1000, 2000 and 4000 Hertz. Results are reported for Part A through Day 29 and Part B through Day 57. The posted results include arm-level means, standard deviations, and counts, but no inferential comparison for this continuous endpoint. No secondary outcome results are posted. Safety results include serious adverse-event counts and report no deaths in the four safety groups.

The registry does not report the statistical analysis plan, analysis populations, missing-data handling, multiplicity strategy, or reasons for differences between endpoint and safety counts. The posted results therefore support descriptive interpretation, with important limits on conclusions about comparative effects.