A Study to Evaluate the Safety and Pharmacokinetics of Ataluren in Participants From ≥6 Months to <2 Years of Age With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Pharmacokinetics of Ataluren in Participants From ≥6 Months to <2 Years of Age With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) (NCT04336826), a na phase 2 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

The clinical question is descriptive rather than comparative. The registry record identifies ataluren exposure and adverse-event monitoring as the focus, alongside pharmacokinetic measures. It does not list a placebo or active comparator, and it does not identify a comparative efficacy endpoint. Consequently, the reported safety counts describe events observed among participants in the ataluren group; they cannot establish how those counts would compare under a different treatment or no treatment.

The primary endpoint is the number of participants with TEAEs, with the registry defining a TEAE as an adverse event that occurred or worsened while participants were taking ataluren, beginning on or after the first dose and extending up to 4 weeks after the last dose. The primary endpoint timeframe is listed as baseline up to Week 28. The record also lists pharmacokinetic outcomes, including measures of exposure, maximum concentration, time to maximum concentration, and trough concentration. Results for those measures are not reported in the registry record.

3. Trial Design

This was a Phase 2, open-label, single-group study of ataluren in male children aged ≥6 months to <2 years with nmDMD. The registry record lists 6 participants as enrolled and marks the study completed. There was no allocation to treatment groups and no masking. All participants in the listed group received ataluren oral suspension on a daily schedule for 24 weeks: 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening.

An open-label design means that treatment assignment was not masked. A single-group design means there was no concurrent control arm. These design features fit a study focused on safety, tolerability, and pharmacokinetics in a young population, but they limit what can be inferred from comparisons: the registry record does not offer a randomized treatment contrast or a control-group estimate. Any adverse-event counts are therefore descriptive of the observed participants and follow-up, not estimates of a difference between treatments.

The primary endpoint is the number of participants with TEAEs, with a timeframe from baseline up to Week 28. The registry defines the safety analysis set as participants who received at least one dose of ataluren. The record also lists pharmacokinetic outcomes for ataluren: AUC from time 0 to 24 hours, AUC over the dosing interval, maximum concentration, time to maximum plasma concentration, and trough concentration. Numerical results for these pharmacokinetic outcomes are not reported in the registry record.

The study start date is 2021-12-29, and the primary completion date is 2023-08-07. Sample-size justification, planned interim analyses, and a detailed statistical analysis plan are not reported in the registry record. The record does not describe procedures for selecting participants beyond the stated age range, sex, and diagnosis. Additional detail about adherence, dose changes, or the handling of treatment interruptions is 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

Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all participants who received at least 1 dose of ataluren.

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: Safety analysis set included all participants who received at least 1 dose of ataluren.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs), measured over Baseline up to Week 28.

The primary endpoint counts participants who experienced at least one treatment-emergent adverse event during the specified observation period. It is a participant-level count, not a count of every event experienced. An adverse event is defined broadly in the registry as an untoward medical occurrence associated with drug use, whether or not considered drug related. A TEAE is an event that occurred or worsened while on ataluren, beginning on or after the first dose and continuing through 4 weeks after the last dose. The primary endpoint timeframe is baseline up to Week 28.

Participant counts are useful in safety monitoring because they indicate how many people in the observed treatment group had an event meeting the endpoint definition. The measure does not, by itself, describe how many events each participant experienced, how severe each event was, or whether ataluren caused an event. The registry separately defines serious adverse events (SAEs) using criteria such as death, life-threatening events, inpatient hospitalization or its prolongation, substantial persistent disability, congenital anomaly or birth defect, and important medical events.

The primary endpoint is not a measure of treatment efficacy. The registry record does not report a clinical efficacy endpoint or a control-group comparison. The count therefore addresses observed safety events in this group, not whether treatment changes disease outcomes. The registry’s adverse-event summary also separates serious events from other, nonserious events and reports those regardless of causality; those categories should not automatically be treated as identical to the primary TEAE endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is a count of participants with TEAEs. This is a binary outcome at the participant level: a participant either meets the endpoint definition during the specified period or does not. It is distinct from a total event count, because a participant with multiple events is still counted as a participant with an event for this endpoint. The registry labels the measure as a count of participants and gives its unit as participants.

Participant counts are straightforward to describe, but their interpretation depends on a clear event definition, observation period, and analysis population. Here, the registry defines a TEAE by its timing during or after ataluren exposure and specifies a timeframe from baseline up to Week 28. Its stated safety analysis set includes participants who received at least one dose. The registry does not report individual event histories or a more detailed account of how the primary endpoint was analyzed.

What can a single-group design estimate?

A single-group study can describe outcomes observed among participants receiving the study treatment. Without a concurrent control group, it cannot directly estimate a treatment difference. The observed adverse-event counts may reflect treatment, the underlying disease, other exposures, or circumstances not separated by the design. Open-label treatment also means the study was not masked, as recorded in the registry. These features do not make the counts unusable; they define them as descriptive safety observations rather than comparative evidence.

For a comparative study, an analysis might estimate a difference between groups and quantify uncertainty around that difference. No such contrast is available in this single-group record. The registry record does not report a prespecified comparative analysis or an inferential estimate for the primary endpoint. It also does not report a confidence interval or p-value for the adverse-event counts.

How should precision be understood?

Precision concerns how much uncertainty surrounds an estimate. In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but interpretation still depends on the study design and the population represented. No confidence interval is reported in the registry record for the safety counts, so the extent of statistical uncertainty is not quantified there.

The limited enrollment is relevant to precision: the observed counts may not characterize uncommon events or variation across a wider population. This is a general limitation of drawing broad conclusions from a small group, not a claim that an unobserved event did or did not occur outside the study. The registry does not report a sample-size justification, so the reason for the enrollment target and its intended precision are not reported in the registry record.

What do the planning illustrations mean?

The planning illustrations are not the study’s observed power and do not describe the design actually used. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Those assumptions describe a hypothetical two-arm planning exercise, whereas this study is recorded as a single-group, nonrandomized study with no comparator. The illustrations should therefore not be read as the protocol’s sample-size plan, nor as evidence that the study had a particular probability of detecting an effect.

In general, sample-size planning asks how much information a future study would need under explicit assumptions about the effect, variability, significance threshold, and desired power. Such calculations are conditional on the assumptions; they do not show what the completed study actually found. A planning estimate also cannot replace an analysis of observed results. The registry record does not report a protocol-based sample-size calculation or a statistical justification for the enrollment.

What analysis details are absent?

The registry record does not report the statistical analysis plan, model specifications, handling of missing observations, interim analyses, or multiplicity procedures. It does not report analysis entries for the listed outcomes. Without those details, readers cannot determine whether particular analyses were prespecified, how incomplete outcome information was handled, or whether any adjustments were planned for examining multiple outcomes. These omissions do not establish that no procedures existed; they mean those procedures are not reported in the registry record.

For the pharmacokinetic outcomes, the record lists AUC0-24, AUC0-τ, Cmax, Tmax, and Ctrough, but numerical estimates and analysis details are not reported in the registry record. The names identify types of pharmacokinetic measures; they do not provide evidence about the observed exposure values or their variability. Interpretation of those measures would require the posted estimates and relevant analysis details.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Ataluren")
n      <- c(6)
events <- c(5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Ataluren  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary safety endpoint and several pharmacokinetic outcomes. Examining multiple outcomes can raise a multiplicity question: when several statistical tests are considered together, the chance of at least one apparently notable result can differ from the chance associated with a single test. As a general matter, a study may prespecify a hierarchy, adjustment method, or descriptive approach to address this issue. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how multiplicity was addressed.

Missing-data handling is also not reported in the registry record. The record states that the safety analysis set includes participants who received at least one dose of ataluren, but it does not describe how incomplete follow-up, unavailable event information, or missing pharmacokinetic measurements were handled. The counts should therefore be read alongside the stated analysis population, without assuming an unreported imputation or exclusion procedure.

The registry record does not report a detailed statistical analysis plan, analysis populations beyond the stated safety set, or analysis entries for the listed outcomes. It also does not report planned interim analyses. These are reporting gaps, not proof that no plans or procedures existed. They limit the ability to assess prespecification, reproduce the analyses, or judge how missing observations and multiple outcomes may have affected interpretation.

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 non-serious adverse event terms

The serious adverse-event summary lists 0 participants with an SAE among 6 at risk, and 0 deaths. The summary lists 5 participants with other, nonserious adverse events among 6 at risk. These figures are participant counts for the ataluren group, not totals of individual events. The SAE and other-event categories are reported regardless of causality.

The registry defines an SAE by specified criteria, including death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant disability, congenital anomaly or birth defect, or another important medical event. The primary endpoint, however, is the number of participants with TEAEs. The record’s definition of TEAEs depends on timing relative to ataluren exposure, while the adverse-event summary is described as covering events regardless of causality. The categories should not be assumed to match without an explicit statement in the record.

A count of 0 reported SAEs does not establish that serious events cannot occur, and the count of other events does not establish that ataluren caused them. The record does not list serious-event terms or provide further event-level details. No comparative safety estimate is available because the study had no control group.

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

The study provides a description of safety monitoring in a group of male children aged ≥6 months to <2 years with nmDMD who received ataluren. The registry reports 0 participants with serious adverse events and 0 deaths, while 5 participants are listed with other, nonserious adverse events. The primary safety endpoint is a participant count for TEAEs over the registry-defined timeframe. These observations are relevant to the study’s stated safety focus, but they do not by themselves establish cause.

The findings do not answer how the observed event counts compare with those under another treatment or no treatment. The study was open-label and single-group, with no comparator. It also does not provide a comparative efficacy estimate. No efficacy outcome result is reported in the registry record, and numerical results for the listed pharmacokinetic outcomes are not reported in the record.

The enrollment of 6 participants means that the observations come from a limited group. They cannot establish the frequency of uncommon events in a broader population, and the record provides no reported confidence interval to quantify uncertainty around the counts. The study’s findings should not be generalized automatically to people outside the stated age range, sex, diagnosis, or study circumstances.

For statistical interpretation, the distinction between observing an event and attributing it to treatment is essential. The registry’s adverse-event summary includes events regardless of causality, while the primary endpoint is defined by occurrence or worsening during a specified exposure-related period. Neither an event count nor the absence of a reported event is, on its own, a causal estimate. The registry record also does not report a detailed analysis plan, missing-data procedures, or multiplicity handling, which limits assessment of how the results were analyzed.

14. Why This Trial Matters Statistically

Statistically, this study matters as a descriptive safety and pharmacokinetic investigation in a narrowly defined young population. The registry records an open-label, single-group design and a safety endpoint based on the number of participants with TEAEs. The design determines the kind of conclusion the data can support: it can describe observed outcomes in the ataluren group, but it cannot provide a randomized comparison or a treatment-effect estimate against a control.

The study also highlights the importance of distinguishing participant counts from event counts. A participant-level endpoint records whether an individual experienced an event meeting the definition; it does not show the number of events per person or characterize their timing and severity. The separate reporting of serious and other adverse events gives a different descriptive view, but the relationship between those categories and the primary TEAE endpoint should not be assumed beyond the definitions in the registry.

Enrollment of 6 participants limits the breadth of the evidence. Even when counts are reported clearly, a limited group may not reveal uncommon events or capture the range of outcomes in a wider population. Because the registry does not report confidence intervals for the counts, statistical precision is not quantified. This makes it especially important to treat the results as observations from this study rather than as stable estimates for other settings.

Finally, the listed pharmacokinetic outcomes show that drug exposure was part of the study’s stated purpose, while their numerical results are not reported in the registry record. The case illustrates why outcome definitions, analysis populations, missing-data procedures, and planned statistical methods matter: without the relevant results and methods, readers can describe what was recorded but cannot fully assess the strength or reproducibility of the statistical evidence.

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.

The most important limitation is the absence of a comparator. With a single treatment group, the registry record cannot separate the observed safety experience under ataluren from what might have occurred under another treatment or no treatment. The open-label design also means masking was absent, as recorded in the study design. Neither feature supports a randomized comparative interpretation.

The enrolled population was limited to male children aged ≥6 months to <2 years with nmDMD. The registry reports enrollment of 6 participants, so the observed counts describe a limited group. They may not capture uncommon events or represent people outside the stated population. The record does not report further population characteristics that would allow assessment of how closely participants represent a broader clinical population.

Some relevant details are not reported in the registry record: a sample-size justification, a detailed statistical analysis plan, interim-analysis plans, missing-data procedures, multiplicity handling, and analysis entries for the outcomes. Numerical results for the pharmacokinetic outcomes are also not reported. The registry lists no serious-event terms, and it does not give event-level details that would clarify timing, severity, duration, or the relationship between reported adverse-event categories and the primary TEAE endpoint.

The safety counts are reported regardless of causality and should not be interpreted as causal effects. The record does not report confidence intervals for these counts, leaving their statistical precision unquantified. The listed planning assumptions are for an illustration involving equal allocation between two arms, whereas the actual study was single-group; those assumptions should not be mistaken for the study’s own design or sample-size rationale.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Pharmacokinetics of Ataluren in Participants From ≥6 Months to <2 Years of Age With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) — NCT04336826.
• Registry record last updated 2024-04-01; status last verified 2024-02.
• Results first posted 2024-04-01.
• 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 registry record describes a completed Phase 2, open-label, single-group study of ataluren in male children aged ≥6 months to <2 years with nmDMD. Enrollment was 6. Participants received oral suspension daily for 24 weeks at 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening. The primary endpoint was the number of participants with TEAEs, with a timeframe from baseline up to Week 28.

The safety summary lists 0 participants with serious adverse events among 6 at risk, 0 deaths, and 5 participants with other, nonserious adverse events among 6 at risk. The registry also lists pharmacokinetic outcomes, but their numerical results are not reported in the registry record. A comparator, detailed statistical analysis plan, sample-size justification, and procedures for missing data or multiplicity are not reported in the registry record. The available safety counts are descriptive and do not provide a comparative treatment estimate.