SENS-401 to Prevent the Ototoxicity Induced by Cisplatin in Adult Subjects With a Neoplastic Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SENS-401 to Prevent the Ototoxicity Induced by Cisplatin in Adult Subjects With a Neoplastic Disease (NCT05628233), a randomized phase 2 study. The primary outcome is SENS-401 Efficacy Assessment With Change From Baseline of the Average of the Hearing Threshold 4 Weeks After the Completion of Cisplatin Treatment in Each Eligible Ear of Each Subject.

2. Clinical Question

The study addresses whether hearing-threshold changes differ between people receiving SENS-401 and those receiving cisplatin-based chemotherapy alone. Hearing was assessed at baseline, before the first cisplatin dose, and after completion of cisplatin treatment. The primary assessment averages measurements across 8-10-12.5 kHz in each eligible ear.

This is an efficacy question about a measured hearing outcome, not a direct measure of every aspect of hearing or of all possible effects of cisplatin. The registry record describes a randomized, controlled, open-label study and includes safety assessment as well as efficacy assessment. The results describe the posted measurements and their uncertainty; they do not by themselves establish that an observed difference is attributable to SENS-401.

3. Trial Design

This is a phase IIa, multicenter, randomized, controlled, open-label study with a parallel two-arm design. The registry record gives an enrollment of 48 and a status of completed. The study start date is 2022-12-30, and the primary completion date is 2025-04-16. These registry entries describe the study record; they do not establish how many participants contributed data to any particular analysis.

Eligible adults had neoplastic disease requiring cisplatin treatment as part of their chemotherapy protocol plan. The control arm received cisplatin-based chemotherapy without SENS-401. The treatment arm received 43.5 mg of oral SENS-401 b.i.d for up to 23 weeks along with cisplatin-based chemotherapy. Randomization was used to assign participants to the arms, but the study was open label, meaning masking was not used.

The primary outcome assessed change from baseline in average hearing threshold 4 weeks after completion of cisplatin treatment. The registry also lists a secondary hearing-threshold assessment at 12 weeks after completion. Audiometry was conducted at baseline and at the post-treatment assessment times described in the record. The primary analysis population was the Full Analysis Set extended to eligible ears of randomized subjects, so the analysis unit described for the primary outcome includes eligible ears rather than being limited to a single summary per participant.

Details such as the allocation ratio, the original sample-size justification, and the specific randomization procedure are not reported in the registry record. The trial’s own statistical plan and the handling of deviations from the planned intervention are also not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) population was extended to the eligible ears of the randomized subjects for the primary analysis.

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.

Population: The Full Analysis Set (FAS) included all randomized participants. One (1) participant randomized in Arm B was excluded from the FAS due to failure to take at least one dose of SENS-401 and the lack of any data post randomization. Twenty three (23) participants who received at least one dose of SENS-401 and all twenty four (24) participants randomized to control arm, were included in the FAS.

6. Primary Endpoint

The registry lists the primary outcome as SENS-401 Efficacy Assessment With Change From Baseline of the Average of the Hearing Threshold 4 Weeks After the Completion of Cisplatin Treatment in Each Eligible Ear of Each Subject, measured over 4 weeks after the completion of cisplatin treatment.

The primary endpoint is the change from baseline in average hearing threshold, measured in decibels using pure tone audiometry, at 4 weeks after completion of cisplatin treatment. The threshold is averaged over three contiguous frequencies, 8-10-12.5 kHz, for each eligible ear. Baseline measurement occurred before the first cisplatin dose.

Pure tone audiometry is a behavioral, subjective hearing test that assesses the sound level at which a person can hear tones at different frequencies. The registry defines a decrease in hearing threshold as an improvement and an increase as a deterioration. The endpoint therefore focuses on whether the hearing threshold changes after cisplatin treatment, and whether the amount of change differs between the arms.

A continuous endpoint retains the magnitude of each measured change rather than reducing the outcome to categories such as improved or worsened. Reporting a mean change allows comparison of the average measured response between groups, while uncertainty estimates help indicate how precisely that difference has been estimated. Because the primary analysis extends the Full Analysis Set to eligible ears, the interpretation concerns the ear-level measurements specified for analysis. It should not be read as a comprehensive measure of hearing function or of every possible manifestation of ototoxicity.

7. Results Posted in the Registry

• Arm B (Treatment Arm): mean 16.80 versus 13.20 on control; difference 3.60 (95% CI -4.16 to 11.36), standardized effect d = 0.32; z-test p = 0.363.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

SENS-401 Efficacy Assessment With Change From Baseline of the Average of the Hearing Threshold 12 Weeks After the Completion of Cisplatin Treatment in Each Eligible Ear of Each Subject.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Arm B (Treatment Arm): mean 14.90 versus 10.00 on control; difference 4.90 (95% CI -2.46 to 12.26), standardized effect d = 0.45; z-test p = 0.192.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm B (Treatment Arm) and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists a secondary hearing-threshold assessment at 12 weeks after cisplatin treatment was completed. Its group estimates and comparison indicate the same broad direction as the primary result: the treatment-arm mean change is numerically higher than the control-arm mean change. The secondary comparison remains uncertain, with its interval including zero. This directional consistency does not remove the uncertainty in either assessment, nor does it establish a treatment effect.

The secondary result relates to the primary finding by measuring the same general hearing-threshold construct at a later post-treatment time. It can add information about whether the pattern is present beyond the primary assessment time, but it is not a substitute for the prespecified primary outcome. The time point differs, and the number of contributing observations described for the secondary analysis differs from that for the primary assessment. Those results should not be treated as interchangeable measurements.

Unadjusted secondary results generally carry less weight for confirmatory conclusions because they may be among multiple outcomes or time points examined. If many comparisons are considered without a prespecified strategy or multiplicity adjustment, the chance of at least one apparently notable result can increase. General statistical context: multiplicity procedures manage that risk by adjusting interpretation or testing thresholds, though the appropriate approach depends on the trial’s analysis plan.

The registry record does not report a multiplicity strategy or a hierarchy governing the secondary outcome. Accordingly, the secondary finding is best treated as supportive descriptive evidence rather than independent confirmation of the primary result. The posted results do not establish whether the later pattern reflects a persistent effect, measurement variation, or other factors.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• SENS-401 Efficacy Assessment With Change From Baseline of the Average of the Hearing Threshold 12 Weeks After the Completion of Cisplatin Treatment in Each Eligible Ear of Each Subject.

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a mean change in hearing threshold measured in dB. For a continuous outcome, group summaries describe the average measured value, while a comparison estimates how far apart the group averages are. The primary arm summaries are least-squares means, and their reported dispersion is the standard error. A standard error describes the uncertainty in an estimated mean; it is not the spread of individual hearing measurements.

What does the mean difference represent?

The reported comparison is the treatment-arm mean minus the control-arm mean. A positive estimate means the treatment-arm change is higher on the numerical scale than the control-arm change. Since the registry says a rise in hearing threshold is deterioration, a positive mean difference points in that direction for the measured outcome. It is an average contrast, not a statement that every eligible ear changed by the same amount. Nor does it establish that treatment caused the difference.

The unadjusted re-calculation uses the posted group summaries to estimate a simple difference between arm means and its uncertainty. Its estimates are 3.6 dB for the difference, a 95% confidence interval from -4.161 to 11.36, and p = 0.363. This is a re-calculation from summary statistics, not the trial’s fitted analysis model. The registry’s own analysis uses ANCOVA and reports a net mean difference. The model’s covariates and other fitting details are not reported in the registry record.

Why are the analyses not identical?

An analysis of covariance, or ANCOVA, estimates an arm contrast while accounting for other variables included in the model. The registry labels its result a net mean difference and reports a 95% confidence interval from -3.7 to 11.0 with p = 0.314. Without the model specification, it is not possible to identify which variables were included or to reproduce the sponsor’s analysis. A difference between an adjusted model result and a simple unadjusted re-calculation can arise because they answer related but not identical statistical questions. The posted ANCOVA result is the sponsor’s analysis; the recalculation is a complementary unadjusted check.

How should a confidence interval be read?

A confidence interval gives a range of values compatible with the data under the analysis assumptions and communicates uncertainty about the estimated contrast. A narrower interval indicates greater precision than a wider interval. Here, the intervals include zero, the value corresponding to no mean difference on the scale used. They also include values on either side of zero. This means the results do not pin down the direction or size of the underlying contrast precisely. A confidence interval is not a guarantee that the true value lies within its endpoints, and it does not indicate the probability that a particular effect is true.

What does the p-value add?

A p-value describes how unusual the observed data, or data more extreme, would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor does it measure the probability that the result happened by chance. The unadjusted p-value and sponsor-reported p-value come from different analyses. Neither should be interpreted without considering the estimated effect, its interval, the model, and the clinical context. The registry does not report a multiplicity adjustment for the outcome analyses.

Why can over-dispersion matter?

General statistical context: over-dispersion means that the observed variability is greater than a model’s assumptions allow. When a model understates variability, standard errors can be too small and intervals too narrow, creating an overly confident impression. For a continuous hearing-threshold outcome, the choice of model and variance assumptions can affect uncertainty estimates. The registry record does not report an over-dispersion assessment for this endpoint, and the posted summary statistics do not permit a separate evaluation of that assumption.

The primary analysis is extended to eligible ears, which means ear-level observations are relevant to the stated analysis population. If two ears from the same participant contribute, their measurements could be correlated. General statistical context: correlated observations contain less independent information than the same number of unrelated observations, and a model may need to account for that dependence. The registry record does not report how within-participant correlation was handled in the ANCOVA or the re-calculation.

These methods describe how to read the estimates, not a full reconstruction of the trial analysis. The registry’s details on covariate selection, missing-data handling, multiplicity control, and model diagnostics are not reported in the registry record. The posted findings should therefore be interpreted with attention to both their uncertainty and the limits of the available analysis description.

11. Confidence Intervals and Precision

The primary sponsor-reported estimate is a net mean difference of 3.6 dB, with a 95% confidence interval from -3.7 to 11.0. The unadjusted re-calculation is 3.6 dB, with a 95% confidence interval from -4.161 to 11.36. Both intervals include zero, so neither estimate rules out no mean difference under its analysis. The intervals also permit differences in either direction, indicating limited precision about the direction and magnitude of the contrast.

A confidence interval is a range produced by a statistical procedure that, under its assumptions, would contain the target parameter in the stated proportion of repeated applications. For a reader, it is useful as a gauge of estimation uncertainty: values closer together indicate a more precise estimate, while a wider span indicates less precision. The interval should not be read as a range containing every individual participant’s or ear’s change, or as a probability statement about the true value.

The two intervals differ because one comes from the registry’s ANCOVA and the other from a simple unadjusted re-calculation based on posted summaries. The sponsor analysis is the trial’s reported analysis, while the recalculation provides a separate check using less information about the model. The registry does not report enough ANCOVA detail to explain the difference in interval endpoints or independently reproduce the fitted model.

Precision also depends on the analysis population, measurement variability, and the assumptions used to estimate uncertainty. The primary analysis is described as the Full Analysis Set extended to eligible ears. The registry record does not report the handling of within-participant correlation or missing observations in sufficient detail to assess their influence on the confidence interval. The interval is therefore best understood alongside the stated analysis and these limits on available methodological detail.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect and are not the trial’s original design calculation. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set at the stated fraction of the observed effect.

For planning at 100% of the observed effect, the figures are 152 participants per arm for 80% power and 204 participants per arm for 90% power. For planning at 75% of the observed effect, they are 271 participants per arm for 80% power and 362 participants per arm for 90% power. For planning at 50% of the observed effect, they are 608 participants per arm for 80% power and 814 participants per arm for 90% power.

In plain terms, 80% power describes a design that would have an 80% chance of detecting the specified effect at the stated significance level if that effect and the planning assumptions were correct. The 90% column describes a higher chance of detecting that effect under the same assumptions, which generally requires more participants. As the target effect becomes smaller, the groups need more participants to distinguish it from random variation.

These calculations are planning illustrations, not observed power. The trial’s original sample-size assumptions and justification are not reported in the registry record. The figures rely on the observed effect as a planning input, so they should not be interpreted as evidence that the trial was designed around those assumptions or that its observed result had a particular probability of being detected.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 3.600; pooled standard deviation σ = 11.200.
2. n = 2 × (1.96 + 0.842)² × 11.200² / 3.600² = 151.9, rounded up to 152 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 3.6                      # observed difference in means
sigma <- 11.2                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5628233)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 152 (80% power), 204 (90% power)
 75% of observed effect: n per arm = 271 (80% power), 362 (90% power)
 50% of observed effect: n per arm = 608 (80% power), 814 (90% power)
power.t.test: 152.9 
Simulated power at n = 152 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s own primary analysis is an ANCOVA. It reports a net mean difference of 3.6 dB, with a 95% confidence interval from -3.7 to 11.0 and p = 0.314. This is the sponsor-reported analysis and is the main posted inferential result for the primary outcome.

The unadjusted re-calculation uses the posted arm summaries rather than the ANCOVA model. It estimates a mean difference of 3.6 dB, with a 95% confidence interval from -4.161 to 11.36 and an unadjusted p-value of 0.363. It is a useful arithmetic check on the group summaries, but it does not reproduce an adjusted model or incorporate covariates whose details are not reported in the registry record.

The estimates are close in their central value and both intervals include zero. Their differing uncertainty limits and p-values reflect the fact that the calculations are not identical analyses. The registry does not give enough information about the ANCOVA specification to explain the precise differences. The posted sponsor result should be interpreted as the study’s own analysis, and the recalculation as a secondary, unadjusted perspective rather than a replacement.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when more than one outcome, time point, subgroup, or statistical comparison is examined. General statistical context: with repeated testing, the chance of a false-positive finding across the family of tests can be higher than the nominal error rate for any one test. A prespecified outcome hierarchy or an adjustment procedure can help control how multiple results are interpreted. The registry record does not report whether such a strategy was used for the primary and secondary hearing outcomes.

The record identifies a primary endpoint at 4 weeks after completion of cisplatin treatment and a secondary assessment at 12 weeks. It does not report a complete statistical analysis plan, the intended testing sequence, or whether the reported p-values were adjusted for multiple comparisons. The secondary result should therefore be interpreted cautiously and should not be treated as an independently confirmatory finding.

Missing-data methods are also not reported in the registry record. The outcome summaries do not explain why observations may be unavailable at an assessment, how missing values were handled, or whether sensitivity analyses were conducted. Missingness can matter if the availability of measurements is related to hearing change, treatment, or other participant characteristics. Without those details, the influence of missing observations on the estimated differences cannot be determined.

The primary population is described as the Full Analysis Set extended to the eligible ears of randomized subjects. That description clarifies the stated analysis population, but the registry does not provide a full definition of the Full Analysis Set, the rules determining an eligible ear, or the handling of participants or ears with incomplete assessments. These details limit independent assessment of which observations contributed to each estimate.

The registry also does not report model covariates, an analysis of within-participant dependence between ears, or sensitivity checks for model assumptions. These are not evidence that a particular method was or was not used; they are details not reported in the registry record. Interpretation should remain tied to the reported analyses and acknowledge that the methodological description is incomplete.

16. 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: neutrophil count decreased (13.0%), acute kidney injury (13.0%), vomiting (12.5%), decreased appetite (8.7%), anaemia (4.3%).

The registry reports serious adverse events in both arms. In the control arm, 8 of 24 participants at risk were affected; in the SENS-401 arm, 15 of 23 participants at risk were affected. Deaths were recorded as 0 in each arm. These are serious adverse-event summaries, not counts of every adverse event or a direct estimate of causation.

The most frequently listed serious terms include neutrophil count decreased and acute kidney injury, each reported as 13.0%; vomiting, 12.5%; decreased appetite, 8.7%; anaemia, 4.3%; and febrile bone marrow aplasia, 4.3%. The registry reports the terms and percentages, but does not establish from these figures alone whether an event was caused by SENS-401, cisplatin, the underlying disease, or another factor.

Comparisons of serious-event counts should be read with the reported numbers at risk in mind. The registry record does not provide enough detail to determine event timing, duration, severity beyond the serious-event classification, or how overlapping events in one participant were counted. These figures describe the posted safety record and do not, by themselves, establish the overall safety profile of either treatment approach.

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

The primary result estimates an average difference in hearing-threshold change between the randomized arms at the specified post-cisplatin assessment. The sponsor’s ANCOVA estimate is 3.6 dB, with a 95% confidence interval from -3.7 to 11.0. The interval includes zero and is broad enough to leave uncertainty about the direction and size of the difference. The posted findings do not establish a clear difference between arms on this measured endpoint.

That uncertainty should not be mistaken for proof that the treatments are equivalent, or proof that there is no effect. Demonstrating equivalence or ruling out meaningful differences would require an appropriate design and prespecified margins, which are not reported in the registry record. Conversely, a numerical difference between arm estimates is not by itself proof of a causal effect. The estimate is subject to sampling variation and the assumptions of the analysis.

The outcome concerns average hearing-threshold change across specified frequencies in eligible ears, rather than all dimensions of hearing or all consequences of ototoxicity. A mean can also conceal variation among participants and ears. The registry record does not state a threshold for clinical importance, so the clinical meaning of a difference of this size cannot be determined from statistical significance alone.

The result applies to the population and treatment context studied: adults with neoplastic disease requiring cisplatin-based chemotherapy. The record describes a phase IIa, open-label, randomized study. It does not establish what would happen in other populations, with other chemotherapy regimens, or at assessment times outside those posted. The secondary assessment offers information at a later time, but it carries the limitations of a secondary comparison and does not remove uncertainty in the primary finding.

Safety summaries are also descriptive. Serious adverse-event counts do not determine whether an event was caused by a study treatment, and the registry figures do not capture every consideration needed to characterize safety. Overall, the posted results provide an estimate of hearing-threshold change and its uncertainty, not medical advice or a definitive conclusion about treatment benefit.

18. Why This Trial Matters Statistically

This trial addresses a measurable adverse effect associated with cisplatin treatment: hearing impairment due to ototoxicity. A randomized comparison with a control arm receiving cisplatin-based chemotherapy without SENS-401 creates a framework for comparing hearing-threshold changes in the study population. The open-label design and the use of an objective-seeming but behavioral, subjective audiometry assessment are relevant context when interpreting the results.

Statistically, the example highlights why the estimate, confidence interval, and analysis method should be considered together. The primary estimate is positive, but its confidence interval includes zero and spans effects in either direction. A p-value by itself would not convey the range of differences compatible with the analysis. The sponsor’s ANCOVA and the unadjusted re-calculation also illustrate that model-based and summary-statistic comparisons can be similar in broad direction without being interchangeable.

The ear-level analysis population is another important feature. When outcomes are recorded for eligible ears, the analysis must consider how ears relate within participants. The registry record does not report how that dependence was handled, which limits methodological appraisal and underscores the value of transparent analysis descriptions.

The planning illustrations also show how sample-size requirements depend on the target effect and desired power. Smaller target effects require more participants under the stated planning assumptions. Those illustrations are not a substitute for the original study design justification, which is not reported in the registry record, and they should not be used to infer observed power.

Together, these features make the trial useful for statistical interpretation: it provides a treatment comparison, repeated hearing assessments, a continuous endpoint, model-based analysis, and uncertainty estimates, while leaving important details about multiplicity, missing data, and model specification unreported. The appropriate conclusion is therefore bounded by both the posted estimates and the limits of the available methodological record.

19. 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 registry record does not report the ANCOVA covariates, model diagnostics, or how the analysis handled correlation between eligible ears from the same participant. Because the primary population is extended to eligible ears, the treatment of within-participant dependence is a trial-specific methodological detail that affects interpretation of uncertainty.

Missing-data procedures are not reported. The record does not explain why observations might be absent at either post-treatment assessment, how any incomplete outcomes were handled, or whether sensitivity analyses were performed. The rules defining the Full Analysis Set and eligible ears are also not reported in detail. These omissions make it difficult to assess whether the posted estimates could be sensitive to the availability of measurements.

The study was open label, and pure tone audiometry is described as behavioral and subjective. The registry does not report whether audiometry assessors were masked to treatment assignment or how measurement procedures were standardized across centers. The record also does not report a clinically important threshold difference, so the clinical relevance of the estimated contrast cannot be judged against a stated benchmark.

Multiplicity handling for the primary and secondary outcomes is not reported. The record gives a primary time point and a later secondary time point but does not specify a testing hierarchy or adjustment. In addition, the original sample-size justification and design assumptions are not reported in the registry record. The planning illustrations based on the observed effect cannot fill that gap.

The registry reports enrollment and completed status, but those details do not establish how many participants or eligible ears contributed to each analysis. The reasons for differences in analysis availability are not reported. These limitations do not invalidate the posted estimates, but they constrain how fully they can be independently evaluated.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: SENS-401 to Prevent the Ototoxicity Induced by Cisplatin in Adult Subjects With a Neoplastic Disease — NCT05628233.
• Registry record last updated 2026-07-02; status last verified 2026-07.
• Results first posted 2026-07-02.
• 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.

23. Record Summary

NCT05628233 is a completed phase IIa, multicenter, randomized, controlled, open-label, parallel study sponsored by Sensorion. It enrolled 48 adults with neoplastic disease requiring cisplatin-based chemotherapy. The control arm received chemotherapy without SENS-401, while the treatment arm received oral SENS-401 at 43.5 mg b.i.d for up to 23 weeks.

The primary outcome was change from baseline in average hearing threshold at 4 weeks after completion of cisplatin treatment, measured across 8-10-12.5 kHz in eligible ears. The sponsor-reported ANCOVA estimate was a net mean difference of 3.6 dB, with a 95% confidence interval from -3.7 to 11.0 and p = 0.314. The interval includes zero, leaving uncertainty about the direction and magnitude of the difference.

The registry also reports a secondary hearing-threshold assessment at 12 weeks and serious adverse-event summaries for both arms. Details on multiplicity, missing-data handling, ANCOVA specification, and the original sample-size justification are not reported in the registry record.