An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy (NCT02090959), a na phase 3 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This was a Phase 3, single-group extension study of ataluren in participants with nonsense mutation dystrophinopathy. The registry lists no masking and no randomized allocation. Its stated purpose was to collect long-term safety data from male participants who had participated in and completed a previous Phase 3 study of ataluren. Screening and baseline procedures were intended to avoid a gap in treatment between that study and the extension.

The intervention was oral ataluren suspension, given three times daily: 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening. The total daily dose was 40 mg/kg, and treatment could continue for up to 144 weeks. The registry lists 219 enrolled participants. The adverse-event summaries use 218 participants at risk; the record does not explain this difference in reported counts.

The study started on 2014-03-20, and its primary completion date is listed as 2018-06-12. Its status is terminated. The brief summary says the study might be extended by amendment until ataluren became commercially available or clinical development in Duchenne muscular dystrophy was discontinued. A reason for termination is not reported in the registry record.

Because there is no randomized control group, the design supports description of outcomes observed among participants in the extension, not a controlled estimate of treatment effect. Participation was also conditional on completing the preceding study, which is important when considering how well the observed participants represent people who did not enter that earlier research.

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: A total of 221 participants completed the double-blind Phase 3 Study PTC124-GD-020-DMD. Of the 221 participants who completed Study PTC124-GD-020-DMD, 219 participants were enrolled in this open-label extension study and 218 were treated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.

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: As Treated (AT) population included all participants who received at least 1 dose of ataluren treatment in this extension study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs), measured over Baseline (Day 1) up to 6 weeks post-treatment (Week 150).

The primary endpoint is the number of participants with treatment-emergent adverse events (TEAEs). It is a participant-count outcome: it records whether participants experienced an event in the defined period, rather than counting every occurrence as a separate participant. The safety population is described as the AT population, comprising participants who received at least one dose of ataluren in the extension.

A TEAE is an adverse event that occurred or worsened from the first dose in this study through 6 weeks after the last dose. An adverse event is defined as an untoward medical occurrence in a participant who received study drug, whether or not it was considered causally related to treatment. The registry describes severity grading under CTCAE Version 3.0, from Grade 1 (mild) through Grade 5 (death). It also defines serious adverse events by criteria including death, life-threatening events, hospitalization, persistent or significant disability, congenital anomaly, and other important medical events requiring intervention.

Counting participants with events is useful for safety monitoring because it indicates how many people were affected during the specified observation period. It does not, on its own, describe event duration, recurrence, timing, or causal attribution. The endpoint details do not give a separately stated overall TEAE result in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group design, so the posted safety findings are most naturally read as counts within the ataluren extension group. A count of participants with an event answers how many people were affected at least once during the specified observation window. It is different from a count of event episodes, since one participant might experience more than one event. The endpoint is defined as a participant count, and the serious and other adverse-event summaries likewise report participants affected.

What does a participant count tell the reader?

A participant count gives a direct description of how many people in the stated safety population had a recorded event. The accompanying denominator matters: it identifies the number of participants at risk in the reported summary. In this record, the adverse-event group uses 218 at risk. The study enrollment figure is 219, and the registry does not explain why the adverse-event denominator differs. No denominator should be inferred for another endpoint unless the record states it.

Counts and percentages are descriptive. A percentage expresses a count relative to a denominator, but neither measure indicates by itself whether an event was caused by treatment. The registry's event definition includes occurrences without regard to the possibility of a causal relationship. Its serious-event summary also includes events regardless of causality. Establishing attribution requires more than observing that an event occurred during a study.

Why is a control group important for comparison?

In a randomized comparison, outcomes in groups assigned to different conditions can be contrasted under the design's assumptions. This extension has no randomized allocation and no concurrent control group. Its event counts therefore describe experience in the ataluren group but cannot estimate a between-group contrast. Differences from an external population would not automatically provide a valid treatment comparison, because populations and observation conditions may differ.

The extension also enrolled participants who had participated in and completed a previous ataluren study. This entry requirement defines the population being observed. People who completed the preceding study may differ from people who did not enter or complete it, so the extension findings should not automatically be generalized to all people with the condition.

How should uncertainty be considered?

In general, a confidence interval describes a range of values compatible with data under a statistical method and its assumptions. It can communicate uncertainty around an estimate, but it does not eliminate design limitations or establish causality. Confidence intervals for the reported adverse-event figures are not reported in the registry record. Statistical tests or adjusted estimates for the primary endpoint are also not reported in the registry record.

In general, event counts can be affected by observation time: participants followed for longer may have more opportunity for an event to be recorded. The registry gives a treatment plan of up to 144 weeks and defines TEAEs through 6 weeks after the last dose. It does not report participant-level follow-up durations or a time-to-event analysis for the primary endpoint. A participant count alone does not account for differences in time under observation.

What does the planning information mean?

General sample-size calculations use assumptions about the effect to detect, allocation, significance level, and statistical method. The registry's planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with planning based on a stated fraction of an observed effect. It characterizes such calculations as planning illustrations, not as the trial's own design. That hypothetical two-arm setup is not the single-group design described for this extension. Any planning illustration should not be read as observed power, a result of this study, or evidence that the extension tested a randomized comparison.

The registry does not report a statistical analysis plan for the primary endpoint in the information. Methods for handling repeated events, adjustment for covariates, estimation of uncertainty, or formal hypothesis testing are not reported in the registry record. Without those details, the most defensible interpretation is descriptive: the stated counts characterize recorded events in the reported group, within the definitions and observation period given.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, including changes in walking distance, timed functional tasks, physical-function scores, and percent predicted forced vital capacity at Week 144. It reports 0 analyses in the information summarized for the record. The multiplicity plan—how statistical inference across several outcomes or analyses would be controlled or interpreted—is not reported in the registry record. When many outcomes are considered, the chance of finding an apparently notable result by chance can increase; this is a general statistical concern, not a claim about the results of this study.

Methods for missing outcome data are not reported in the registry record. The record does not describe imputation, rules for excluding incomplete observations, or sensitivity analyses. Without those details, the consequences of missing measurements for the functional outcomes cannot be assessed. The treatment plan allowed exposure for up to 144 weeks, but the registry does not state that all participants completed that duration or provide a participant-level account of follow-up for these outcomes.

The primary safety population is defined as participants who received at least one dose of ataluren in the extension. The adverse-event summaries give 218 participants at risk, while the registry reports enrollment of 219; the reason for the difference is not reported. The registry record does not describe additional analysis populations or explain how participants without a dose or with incomplete data were handled for each outcome. These reporting gaps limit assessment of how analysis populations and missing observations may affect the results.

11. 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: femur fracture (2.3%), lumbar vertebral fracture (0.9%), spinal compression fracture (0.9%), hypoxia (0.9%), exposure to communicable disease (0.5%).

The serious adverse-event summary reports 24 affected participants among 218 at risk. The summary of other adverse events reports 201 affected participants among 218 at risk, and the death count is 0. These categories should be read as the registry reports them; the record does not establish that participants in one category were excluded from the other. The figures are counts of participants, not totals of event episodes.

The listed serious-event terms are femur fracture (2.3%), lumbar vertebral fracture (0.9%), spinal compression fracture (0.9%), hypoxia (0.9%), exposure to communicable disease (0.5%), and hip fracture (0.5%). These are the terms and percentages reported in the serious-event summary. They do not, by themselves, identify cause, duration, recurrence, or clinical consequence beyond the serious-event classification.

The registry defines serious adverse events using criteria such as death, a life-threatening event, hospitalization, significant disability, congenital anomaly, or another important medical event requiring intervention. Serious-event summaries include events regardless of causality. Therefore, the presence of an event in this list is not evidence that ataluren caused it. The figures are descriptive observations from a single-group extension, without a concurrent control group for comparison.

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

The posted results describe adverse events reported among participants receiving ataluren in a long-term extension. They include counts of participants with serious and other adverse events, a death count of 0, and selected serious-event terms with percentages. The stated primary objective was to obtain long-term safety data and augment the overall safety database.

These observations do not show what would have happened to comparable participants under a different treatment or without ataluren. The study was single-group, with no randomized allocation or masking, so the registry results do not provide a controlled estimate of comparative safety. Nor do the event counts alone determine whether a particular event was caused by study treatment.

The trial also listed functional and respiratory outcomes, including change in 6MWD, timed movement tasks, NSAA and PUL scores, and percent predicted FVC at Week 144. Their presence as outcomes does not establish a result. Values and analyses for these outcomes are not reported in the information available for this account. The record also does not state a separate overall TEAE count in the primary endpoint details.

Interpretation should remain specific to the enrolled extension population: male participants with nonsense mutation dystrophinopathy who had participated in and completed a previous ataluren study. The reported findings do not automatically apply to people who did not enter that prior study, or to populations with different characteristics. The registry lists treatment for up to 144 weeks, not completed exposure of that duration for every participant.

In short, the record supplies descriptive safety information for this extension but does not establish comparative effects, causation, or outcomes beyond those reported. Absence of a reported result in the registry record should not be interpreted as evidence that an outcome did or did not occur.

13. Why This Trial Matters Statistically

Extension studies address a statistical question that differs from an initial controlled efficacy comparison: they can describe events during continued exposure in participants who enter the extension. This study's stated aim was long-term safety data collection, and its endpoint counts participants with treatment-emergent adverse events over a defined period. Clear definitions of the event window and safety population are essential for interpreting those counts.

The record illustrates why denominators and populations matter. Enrollment is reported as 219, while the adverse-event summaries give 218 at risk. The reason for this distinction is not reported. Stating the population used for a safety summary helps readers understand whose experience the result describes, without treating the enrollment figure as the denominator for every analysis.

It also illustrates the limits of descriptive safety evidence. A single-group study can report how many participants had recorded events, but it cannot by itself separate treatment-associated events from events that might occur because of the underlying condition or other circumstances. The registry's definition includes adverse events regardless of causal relationship, making that distinction especially important.

Participants entered after completing a previous study, so selection into the extension shapes the population represented. This matters statistically because findings among extension participants are not automatically generalizable to people who did not take part in or complete the earlier study. The reported event categories and selected terms should therefore be read as observations in this particular study population, not as controlled estimates of risk for a broader population.

The record also makes clear that a stated endpoint and listed secondary outcomes are not equivalent to fully reported numerical results or analysis methods. Without reported uncertainty estimates, missing-data methods, or multiplicity procedures, readers should avoid claims that go beyond the descriptive information available.

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 main design limitation is the absence of a concurrent randomized comparator. The study is single-group and unmasked, so adverse-event counts cannot be used to estimate a causal contrast with another treatment. Event occurrence during treatment does not establish attribution, and the registry explicitly includes adverse events without regard to causal relationship.

The extension population was limited to male participants with nonsense mutation dystrophinopathy who had participated in and completed a previous Phase 3 ataluren study. This selection restricts how broadly the findings can be applied. The study description planned treatment for up to 144 weeks, but the registry record does not report that every participant reached that duration or provide individual follow-up information.

The registry reports 219 enrolled participants and adverse-event summaries with 218 at risk, but does not explain the difference. It does not report a separate overall TEAE count in the primary endpoint details available for this account. Although serious and other adverse-event counts are reported, the record does not clarify whether those categories overlap.

Methods for missing data, confidence intervals, adjusted analyses, and multiplicity are not reported in the registry record. The study status is terminated, but the reason for termination is not reported. These limitations mean the available information supports a descriptive reading of specified safety findings, not a complete assessment of comparative safety or all planned outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy — NCT02090959.
• Registry record last updated 2020-08-11; status last verified 2020-08.
• Results first posted 2020-08-11.
• 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.

18. Record Summary

NCT02090959 is a Phase 3, single-group extension study of ataluren in male participants with nonsense mutation dystrophinopathy who had participated in and completed a previous ataluren study. The primary objective was long-term safety data collection. Ataluren was given orally three times daily at a total daily dose of 40 mg/kg, for up to 144 weeks. The record reports enrollment of 219 and lists the study status as terminated.

The primary endpoint counts participants with treatment-emergent adverse events. Adverse-event summaries report 24 participants with serious events and 201 with other events among 218 at risk; the death count is 0. The registry record does not report a randomized comparator, a separate overall TEAE count in the endpoint details, the reason for termination, or methods for missing data and multiplicity. These findings are descriptive and do not establish causal or comparative effects.