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 AUT00063 Versus Placebo in Age-Related Hearing Loss (NCT02345031), a randomized phase 2 study. The primary outcome is Change in Hearing Loss After 4 Weeks of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02345031 |
| Phase | Phase 2 |
| Condition | Age-Related Hearing Loss |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 78 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Autifony Therapeutics Limited |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned people with age-related hearing loss. Its primary outcome analysis used the Full Analysis Set. The registry record reports enrollment of 78, while the posted primary outcome summaries include 37 participants in the AUT00063 group and 39 in the placebo group. The record does not describe the eligibility criteria in detail, so the age range, hearing-loss thresholds, and other characteristics required for participation are not reported in the registry record.
Intervention
The intervention was AUT00063, described as 600 mg capsules. The regimen was three 200 mg capsules taken orally once daily with food for 4 weeks. The trial was randomized, and its parallel design assigned participants to AUT00063 or placebo. The registry identifies the study as Phase 2.
Comparator
The comparator was placebo, described as three placebo capsules taken orally once daily with food for 4 weeks. The official study title describes a placebo-controlled, double-blind study, while the registry’s masking field states quadruple masking. Further details about which people were masked, or how masking was maintained, are not reported in the registry record.
Primary question
The primary question was whether change in hearing, measured by QuickSIN speech-in-noise performance, differed between AUT00063 and placebo from baseline on Day 1 to Day 28. QuickSIN assesses the signal-to-noise level required for 50% recognition. The posted results give a least-squares mean change and a 95% confidence interval for each group. A direct between-group primary estimate and its statistical test are not reported in the registry record, so the displayed group estimates do not by themselves establish the size or precision of a treatment contrast.
3. Trial Design
This was a randomized, parallel-group Phase 2 study comparing AUT00063 with placebo in age-related hearing loss. The registry record identifies the study as completed and gives enrollment as 78. The recorded start was 2015-01 and primary completion was 2016-05. Autifony Therapeutics Limited is listed as the sponsor.
Participants were assigned to AUT00063 or placebo. The AUT00063 regimen was three 200 mg capsules, taken orally once daily with food for 4 weeks; the placebo regimen used three placebo capsules on the same schedule. The official title characterizes the study as balanced, randomized, placebo-controlled, and double-blind. The registry’s masking field says quadruple masking. These descriptions indicate masking was part of the design, but the identities of the masked groups and operational procedures are not reported in the registry record.
The primary outcome timeframe was 28 days. It assessed change in QuickSIN performance from baseline on Day 1 to Day 28. The analysis population is named the Full Analysis Set. The registry does not report the criteria used to define that set, the randomization procedure, allocation-concealment details, or a statistical analysis plan. It also does not report the planned sample-size justification or whether any interim analyses were planned or conducted.
Posted primary outcome summaries list 37 participants for AUT00063 and 39 for placebo. Safety summaries use at-risk counts of 38 and 40, respectively. These are outcome-specific counts, and the record does not explain the differences in analysis denominators. The design information supports understanding the comparison being made, but it does not fill in unreported details about conduct or 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.
Overall Study
| Stage | AUT00063 (600 mg Capsules) | (AUT00063 Placebo Capsules) |
|---|---|---|
| STARTED | 38 | 40 |
| COMPLETED | 37 | 39 |
| NOT COMPLETED | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set
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 | AUT00063 (600 mg Capsules) | (AUT00063 Placebo Capsules) | Total |
|---|---|---|---|---|
| Participants analysed | 38 | 40 | 78 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 15 | 13 | 28 |
| Age, Categorical: >=65 years | Participants | 22 | 26 | 48 |
| Sex: Female, Male: Female | Participants | 15 | 17 | 32 |
| Sex: Female, Male: Male | Participants | 22 | 22 | 44 |
| Race/Ethnicity, Customized: Race – White/Caucasian | Participants | 36 | 38 | 74 |
| Race/Ethnicity, Customized: Race – Black/African-American | Participants | 1 | 1 | 2 |
| Race/Ethnicity, Customized: Ethnicity – Hispanic Or Latino | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Ethnicity – Not Hispanic Or Latino | Participants | 36 | 39 | 75 |
| Region of Enrollment: United States | Participants | 38 | 40 | 78 |
| QuickSIN SNR-50 Score (dB) | decibels (dB) | 7.00 (SD 1.963) | 7.11 (SD 1.991) | 7.06 (SD 1.965) |
6. Primary Endpoint
The registry lists the primary outcome as Change in Hearing Loss After 4 Weeks of Treatment, measured over 28 days.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | decibels (dB) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change in hearing loss after 4 weeks of treatment, measured in decibels using the QuickSIN test. QuickSIN assesses speech-in-noise performance: it measures the signal relative to background noise needed for 50% recognition. The test was administered in a sound booth at 70-dB HL binaurally through insert earphones. Three lists were administered to each participant, and the threshold was calculated as the mean of the three lists. Each list contains sentences presented in four-talker babble, with signal-to-noise ratios decreasing in 5-dB steps from 25, described as very easy, to 0, described as extremely difficult.
A speech-in-noise measure captures performance under competing sound rather than hearing in quiet alone. That makes it relevant to the trial’s focus on age-related hearing loss and speech understanding in noise. The reported endpoint is a change from baseline, so its interpretation depends on the measurement scale and the direction in which better performance is represented. The registry record describes the threshold but does not explicitly state the clinically preferred direction of change or a threshold for an important difference.
The reported parameter is a least-squares mean, with a 95% confidence interval for each group. Least-squares means are model-based estimates; the model specification and any covariates are not reported in the registry record. The endpoint therefore summarizes the estimated within-group change, but the posted primary results do not include a direct between-group contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the primary QuickSIN outcome, the AUT00063 group’s least-squares mean change was -1.114 dB, with a 95% confidence interval from -1.956 to -0.272. The placebo group’s least-squares mean change was -1.914 dB, with a 95% confidence interval from -2.703 to -1.125. Both group estimates are negative, and their confidence intervals overlap. These are estimates of change within each group; they should not be read as the estimated treatment effect relative to placebo.
The registry record does not report a primary between-group estimate, its confidence interval, or a primary hypothesis test. Without those items, the size and precision of the contrast between AUT00063 and placebo cannot be assessed directly from the posted primary results. Comparing the two group-specific confidence intervals is not a substitute for a confidence interval or test of the difference. The record also does not state a threshold for a clinically important QuickSIN change, so the clinical importance of either group estimate cannot be determined from these results alone.
A confidence interval describes uncertainty around an estimate under the assumptions of the analysis. The interval does not mean that the true value has a 95% probability of lying within the particular reported bounds. Rather, the confidence level refers to the long-run performance of the interval-generating procedure under its assumptions. The reported intervals convey uncertainty in each group estimate, but they do not answer the unreported between-group question.
The posted primary outcome uses the Full Analysis Set, with group-specific analysis counts of 37 and 39. The registry does not describe the rules defining that set or how missing outcome measurements were handled. Consequently, the possible effects of incomplete data, exclusions, or deviations from the assigned regimen cannot be evaluated from the record. The enrollment figure should not be treated as the denominator for every outcome.
The statistical reading is therefore bounded: the registry reports estimated changes and their intervals for each group over the stated timeframe, but does not report the primary contrast needed to quantify the comparative effect. No conclusion about efficacy or lack of efficacy follows solely from the two within-group summaries. Precision, clinical importance, and sensitivity to analysis choices remain uncertain because the relevant comparison and supporting methods are not reported in the registry record.
9. Statistical Methods Explained
The primary outcome is continuous: it is a decibel measure of QuickSIN change. The registry reports least-squares means and 95% confidence intervals for each treatment group. The statistical methods used to calculate those values are not fully described, so interpretation should distinguish the reported summaries from details that are absent.
What does a least-squares mean represent?
In general, a least-squares mean is an estimate derived from a statistical model rather than simply the arithmetic average of observed values. It can account for terms included in that model. Which terms were included, whether the analysis adjusted for baseline or other characteristics, and how the model was fitted are not reported in the registry record. It would therefore be unwarranted to attribute any particular adjustment or modeling choice to these estimates.
The registry gives a least-squares mean for each group, not a direct least-squares mean difference between groups. A treatment comparison ordinarily targets a contrast between groups, with an estimate and uncertainty interval that directly quantify the difference. The posted primary results do not include that contrast or a corresponding test. A reader should not derive a new contrast by subtracting the displayed group estimates: such a calculation would not supply the model-based contrast, its standard error, or the statistical test used by the sponsor.
How should the confidence intervals be read?
In general, a confidence interval gives a range of values compatible with the data and the interval procedure, subject to the analysis assumptions. Narrower intervals indicate greater precision than wider intervals on the same scale. The intervals reported for the primary endpoint describe uncertainty around each group’s estimated change. They do not directly quantify uncertainty in the between-group difference. Overlap or non-overlap of separate group intervals is not itself a formal test of the contrast.
Intervals also do not establish clinical importance. That judgment requires an interpretable scale and a benchmark for meaningful change. The record describes QuickSIN’s measurement process but does not report a clinically important difference threshold. Nor does it state the direction of change considered beneficial. These omissions limit interpretation of the numerical estimates even when their statistical uncertainty is described.
What is the role of the secondary comparison?
The posted pharmacokinetic comparison includes a mean difference, a confidence interval, and an unadjusted p-value. In general, a p-value measures how compatible the data are with a specified null hypothesis under the assumptions of the test; it is not the probability that the null hypothesis is true and does not measure clinical importance. The secondary comparison is a calculation based on posted summary statistics, and the registry lists no reported analyses for that secondary outcome. It should not be treated as a sponsor-reported primary analysis.
The registry record also includes planning illustrations based on the observed secondary effect. These are hypothetical sample-size calculations, not observed power and not evidence that the trial was designed around those assumptions. They use a two-sided significance level of 0.05, equal allocation, a normal approximation, and specified fractions of the observed effect. Such illustrations depend strongly on the assumed effect and model. Smaller assumed effects generally require larger sample sizes to achieve a target power, all else being equal. The actual trial’s sample-size justification is not reported in the registry record.
Why can over-dispersion matter?
In general, over-dispersion occurs when variation in the data exceeds what a model’s assumed distribution allows. If a model ignores that extra variation, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. This concern is especially relevant for count or event outcomes; the primary endpoint is continuous, and the registry does not describe a model or report a dispersion assessment. There is therefore no basis to claim that over-dispersion was or was not present in the primary analysis.
What remains unknown about the analysis?
The registry names the Full Analysis Set but does not define membership or give the handling of missing outcome data. It does not report the primary analysis model, assumptions about repeated or baseline measurements, diagnostic checks, or a prespecified primary contrast. It also does not report a multiplicity procedure. Those details matter because choices about population, model, missing data, and testing can affect both the estimate and the strength of statistical evidence. The posted summaries can be described as recorded, but they do not allow those analytical choices to be independently assessed.
10. Multiplicity, Missing Data and Analysis Populations
The record identifies a primary QuickSIN outcome and several secondary outcomes, including an Adaptive Test of Temporal Resolution measure, safety and tolerability assessments, and pharmacokinetic plasma levels. The temporal-resolution outcome is listed twice. The registry reports five outcome measures but does not describe the full relationship between those measures, the planned hypotheses, or any hierarchy for interpreting them.
When multiple outcomes are tested, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures control or account for that risk by adjusting the testing strategy or by specifying which outcomes are confirmatory and which are exploratory. A multiplicity plan, correction method, or prespecified testing hierarchy is not reported in the registry record. The posted pharmacokinetic comparison is unadjusted. Its p-value should be read as an unadjusted result, not as evidence that the broader family of outcomes was controlled for multiple testing.
The primary summaries are reported for the Full Analysis Set, but the rules defining that population are not reported in the registry record. The primary analysis counts are 37 for AUT00063 and 39 for placebo. The safety summaries use at-risk counts of 38 and 40. Those different outcome-specific denominators should remain distinct; the record does not explain why they differ or provide a participant-flow account that would clarify inclusion, withdrawal, or missing measurements.
The handling of missing primary outcomes is not reported in the registry record. There is no description of imputation, complete-case analysis, sensitivity analyses, or assumptions about why measurements might be missing. The record also does not report the amount or pattern of missing data. These omissions prevent an assessment of whether the posted estimates could be sensitive to missingness or to the definition of the analysis population.
Interim analyses and any adjustments associated with them are not reported in the registry record. Nor is a complete statistical analysis plan available in the record. The absence of these details does not establish that particular procedures were or were not used; it means their use cannot be assessed from the registry information.
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 |
|---|---|---|---|
| AUT00063 (600 mg Capsules) | 0 | 38 | 0.0% |
| Placebo (AUT00063 Placebo Capsules) | 1 | 40 | 2.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| AUT00063 (600 mg Capsules) | 0 of 38 |
| Placebo (AUT00063 Placebo Capsules) | 0 of 40 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| AUT00063 (600 mg Capsules) | 18 of 38 |
| Placebo (AUT00063 Placebo Capsules) | 21 of 40 |
Most frequent serious adverse event terms
| Event term | Organ system | AUT00063 (600 mg Capsules) | Placebo (AUT00063 Placebo Capsules) |
|---|---|---|---|
| Alcohol poisoning | Injury, poisoning and procedural complications | 0 of 38 | 1 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AUT00063 (600 mg Capsules) | Placebo (AUT00063 Placebo Capsules) |
|---|---|---|---|
| Headache | Nervous system disorders | 4 of 38 | 5 of 40 |
| Dizziness | Nervous system disorders | 6 of 38 | 1 of 40 |
| Tinnitus | Ear and labyrinth disorders | 4 of 38 | 3 of 40 |
| Diarrhoea | Gastrointestinal disorders | 3 of 38 | 2 of 40 |
| Nausea | Gastrointestinal disorders | 2 of 38 | 3 of 40 |
| Upper respiratory tract infection | Infections and infestations | 3 of 38 | 2 of 40 |
| Back Pain | Musculoskeletal and connective tissue disorders | 1 of 38 | 3 of 40 |
| Sinus Congestion | Respiratory, thoracic and mediastinal disorders | 1 of 38 | 2 of 40 |
| Somnolence | Nervous system disorders | 3 of 38 | 0 of 40 |
| Blood triglycerides increased | Investigations | 2 of 38 | 0 of 40 |
Serious events with the highest arm-level rate: alcohol poisoning (2.5%).
The safety summaries report serious adverse events separately from other adverse events and give an at-risk count for each group. For AUT00063, the serious adverse event count was 0 among 38 at risk; for placebo, it was 1 among 40 at risk. The record reports 0 deaths in each group. It also identifies alcohol poisoning, with 2.5%, as a top serious-event term. The registry does not provide enough detail to determine the event’s timing, circumstances, or relationship to study treatment.
These counts are descriptive. They do not establish whether an event was caused by the assigned intervention, and the record does not provide an adjudication or causal-assessment narrative. A serious adverse event is a category used for important events under safety-reporting rules; it is not interchangeable with every adverse event or with severity alone. The record also reports other adverse events affecting 18 participants among 38 at risk in the AUT00063 group and 21 among 40 at risk in the placebo group.
Safety comparisons in a trial of this size and duration can be imprecise, particularly for uncommon events. The posted counts should therefore be read as the events recorded during the study, not as a definitive comparison of safety profiles. The registry does not report event-level detail or a statistical comparison for these figures.
12. What the Result Does, and Does Not, Mean
The primary result describes estimated change in QuickSIN performance within each treatment group over 28 days. The estimates and confidence intervals indicate the uncertainty reported for those group-specific changes. Because a direct between-group primary estimate and test are not reported in the registry record, the posted primary summaries do not quantify how much the groups differed or how precisely that difference was estimated.
The result does not establish that AUT00063 improved hearing, nor does it establish that it had no effect. Those conclusions would require a suitable comparative analysis and interpretation against a clinically meaningful benchmark. The registry record does not report a primary contrast or a threshold for meaningful QuickSIN change. The group estimates alone cannot substitute for either piece of information.
The study’s short treatment period and specified QuickSIN task define the scope of the outcome. The record describes testing under speech-in-noise conditions; it does not provide evidence about other aspects of hearing, longer-term outcomes, or effects beyond the stated timeframe. The record also does not report enough participant characteristics to determine how broadly the results apply to people with age-related hearing loss outside the study.
Secondary information has a different role. Pharmacokinetic observations concern plasma levels, while secondary auditory measures and safety assessments address other questions. They may help characterize the study, but unadjusted secondary findings do not replace the primary comparison. The record does not report a multiplicity strategy or analyses for all listed secondary outcomes.
Finally, precision and robustness cannot be fully judged from the registry summaries. The population definition, missing-data handling, primary model, and primary hypothesis test are not reported. The posted estimates are useful descriptions of the recorded outcome, but they should be interpreted within these limits rather than as a standalone verdict about treatment efficacy or safety.
13. Why This Trial Matters Statistically
This trial illustrates why group-specific estimates and a treatment contrast answer different statistical questions. The registry reports least-squares mean changes for AUT00063 and placebo, each with a confidence interval. Those summaries describe estimated change within each group. The principal comparative question, however, concerns the difference between groups. Without that contrast and its uncertainty, readers cannot directly assess the estimated comparative effect from the primary results.
The record also shows why endpoint definitions matter. QuickSIN measures speech recognition against background noise, using a specified threshold and testing procedure. Understanding what the scale represents helps distinguish the measured performance from broader claims about hearing. At the same time, the record does not state a clinically important change threshold or preferred direction, illustrating how a statistical estimate can remain difficult to interpret clinically even when its units and uncertainty are given.
Another statistical issue is the separation of confirmatory and exploratory evidence. The trial includes several secondary domains, but the record does not describe a multiplicity plan or a hierarchy of hypotheses. An unadjusted secondary result may be informative, but its evidential weight is not equivalent to a prespecified primary comparison protected by a transparent testing strategy.
Finally, denominators and analysis populations deserve attention. The primary and safety summaries use different at-risk or analysis counts, and the registry does not explain the difference. The Full Analysis Set is named but not defined, while missing-data methods are not reported. These details affect how confidently readers can connect a reported estimate to the randomized comparison. The trial is therefore a useful example of reading posted results carefully: identify the estimand, distinguish within-group change from between-group effect, and recognize when missing methods limit interpretation.
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 reporting limitation is the absence of a direct between-group QuickSIN estimate, confidence interval, and statistical test in the registry record. Separate group estimates do not provide the same information as a treatment contrast, and their intervals do not directly describe uncertainty in that contrast.
The analysis methods are incompletely described. Although the record names the Full Analysis Set and reports least-squares means, it does not define the analysis population, identify the model terms, or explain how baseline values were handled. The method for handling missing primary outcome data is also not reported. The primary and safety denominators differ, but the record does not explain the difference or give a participant-flow account.
The registry does not report a clinically important QuickSIN threshold or explicitly identify the preferred direction of change. This limits interpretation of the magnitude of the group estimates. The treatment period was 4 weeks, and the primary timeframe was 28 days; results therefore address the recorded short-term outcome rather than longer-term performance.
Several secondary outcomes are listed, including a repeated listing of the Adaptive Test of Temporal Resolution outcome. A multiplicity approach and an outcome hierarchy are not reported. The posted secondary pharmacokinetic comparison is unadjusted, and analyses for the other listed secondary outcomes are not reported in the registry record. The absence of these details restricts how strongly secondary observations can be interpreted alongside the primary result.
The record gives limited information about eligibility, participant characteristics, randomization procedures, masking procedures, and the trial’s sample-size justification. These details are not reported in the registry record, so they cannot be used to assess representativeness, allocation procedures, or the rationale for the planned enrollment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of AUT00063 Versus Placebo in Age-Related Hearing Loss — NCT02345031.
- Registry record last updated 2018-08-09; status last verified 2018-08.
- Results first posted 2017-09-19.
- 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
NCT02345031 is a completed randomized, parallel-group Phase 2 study of AUT00063 versus placebo for age-related hearing loss. The registry lists enrollment of 78, with a start date of 2015-01 and primary completion in 2016-05. The AUT00063 regimen was 600 mg orally once daily with food for 4 weeks; placebo capsules followed the same schedule.
The primary outcome was QuickSIN change from baseline on Day 1 to Day 28, reported as group-specific least-squares means with 95% confidence intervals. The primary between-group estimate and test are not reported in the registry record. The named analysis population is the Full Analysis Set, but its definition and missing-data methods are not reported.
Secondary aims include temporal-resolution performance, safety and tolerability, and plasma levels. Safety summaries report serious adverse events and deaths by group. The registry does not report a multiplicity plan or complete analyses for the listed secondary outcomes, limiting the strength of conclusions that can be drawn from the record.