Safety Study of Oral Edaravone Administered in Subjects With ALS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Study of Oral Edaravone Administered in Subjects With ALS (NCT04165824), a na phase 3 study. The primary outcome is Number of Treatment Emergency Adverse Events.

2. Clinical Question

In practical terms, the study asks what safety and tolerability information is recorded during oral edaravone use in this study group. The registry lists adverse-event counts for the MT-1186 group, including serious adverse events, other adverse events, and deaths. These are descriptive safety findings from a single group, rather than estimates of a treatment effect relative to a control group.

The record does not specify the definition of a treatment-emergent event, the criteria used to classify an event as serious, or the analysis population for the primary outcome. It also does not state how events were attributed to treatment. Those omissions limit how precisely the primary question can be matched to the reported safety counts. The findings can describe what the registry records for this study, but cannot by themselves distinguish events related to treatment from events arising for other reasons.

3. Trial Design

This is a Phase 3, completed, single-group study sponsored by Shionogi. The registry records an enrollment of 185 and identifies ALS as the condition under study. Its start date is 2019-11-18 and its primary completion date is 2021-10-07.

The intervention is MT-1186, described in the study summary as oral edaravone. The stated objective is to evaluate long-term safety and tolerability over 24 and 48 weeks. The primary outcome timeframe is stated separately as up to 48 weeks. The record does not explain how the outcome timeframe relates to the two intervals in the study objective.

There is no concurrent comparator group in the recorded design. Allocation is listed as not applicable, the model is single group, and masking is none. Consequently, the study design does not provide a randomized comparison that would separate the experience of people receiving MT-1186 from the experience of a control group under the same study conditions. The adverse-event findings should therefore be read as observations within the treated group, not as differences between treatments.

The arm description is blank. Further information about dose, dosing schedule, treatment adherence, permitted concomitant care, visit schedule, and follow-up procedures is not reported in the registry record. The record also does not state how participants were selected or whether the enrollment entry represents a planned or final number beyond its presentation as enrollment.

The registry record lists four outcome measures, but contains no analysis records. It does not give a statistical analysis plan, a sample-size justification, or details of any planned interim analyses. The posted sample-size material is a planning illustration based on stated assumptions; it is not evidence that the study was designed around those assumptions or that observed power was assessed. In particular, a hypothetical equal-allocation, two-arm illustration does not describe the single-group design recorded for this trial.

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:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Treatment Emergency Adverse Events, measured over up to 48 Weeks.

The primary endpoint is titled “Number of Treatment Emergency Adverse Events,” measured in events, with a timeframe of up to 48 weeks. As worded, it is a count endpoint: it concerns the number of events rather than a measurement such as a laboratory value or a time-to-event outcome. It is listed as a primary safety outcome, consistent with the study’s stated objective of assessing safety and tolerability.

Event counts can be useful for describing the volume of adverse-event experience observed during treatment. In general, they can convey more than whether a participant had any event, because a participant may experience multiple events. But interpreting a count requires knowing what qualifies as an event, how recurrent events are handled, and whether the count refers to all events or a defined subset. Those details are not reported in the registry record. The primary outcome’s description and population fields are also blank.

The registry provides no primary endpoint estimate, uncertainty interval, or analysis record. Accordingly, the outcome title and timeframe establish what the registry intended to measure, but do not establish the result for that endpoint. The separately listed adverse-event figures are safety summaries; they should not be treated as a reported analysis of this primary event-count endpoint without a stated link between them.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s recorded design determines the kinds of statistical claims that are available. It is a single-group study with no masking and no randomized comparator. The entries for MT-1186 can be described within that group, but they do not provide a direct estimate of the difference between treatment and control. A within-group count answers what was recorded in the group; a comparative effect asks how outcomes differ between groups. Those are distinct questions.

What does a count endpoint represent?

A count endpoint records how many events occur over a defined observation period. General statistical practice distinguishes an event count from a count of participants who experienced at least one event. If one person experiences repeated events, the event count can include each occurrence, whereas the participant count may still represent that person once. The registry calls the primary outcome a number of events, while its safety summary also gives affected-person counts. The relationship between these summaries is not explained in the registry record.

Count data can have different distributions depending on the event process and the way observation is conducted. Some common models assume that the mean and variance are linked in a particular way. Over-dispersion is a general term for more variability in counts than such a model expects. If present, it can make standard errors too small and confidence intervals too narrow when an unsuitable model is used. The registry does not report a model, dispersion estimate, or other analysis for the primary count endpoint, so it is not possible to say whether over-dispersion was assessed or how count uncertainty was handled.

How should uncertainty be understood?

In general, an estimate is a summary of observed data, while a confidence interval expresses uncertainty about that estimate under a specified method and assumptions. A narrow interval indicates greater statistical precision under that method; a wide interval indicates less precision. An interval does not resolve design limitations such as the absence of a comparator, incomplete outcome definitions, or uncertain treatment attribution. The registry record gives no primary endpoint estimate or confidence interval, and no uncertainty intervals for the posted adverse-event figures. No such values can be inferred from the counts without selecting and applying an analysis method, and the registry does not report that method.

A p-value, in general, evaluates how compatible data are with a specified null hypothesis under a statistical model. It does not measure the probability that a treatment works, and it does not remove confounding or other design limitations. The registry includes no analysis records or primary endpoint p-value. There is therefore no reported inferential test to interpret for this outcome.

What does the design permit?

With a single group, the observed safety entries describe what happened among participants recorded in that group. Without random allocation to a concurrent comparator, differences attributable to treatment cannot be separated from other explanations using these entries alone. General external comparisons also require information about comparable populations, outcome definitions, observation periods, and data collection. Such a reference comparison is not reported in the registry record.

Masking is recorded as none. In general, lack of masking can affect how outcomes are noticed, assessed, or reported, particularly when an outcome depends on judgment or participant reporting. The registry does not provide enough detail to determine whether or how this issue affected the event collection in this study.

How should planning illustrations be read?

Sample-size calculations are planning tools, not results. The stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. Those assumptions describe a hypothetical planning exercise, not the recorded single-group study design. Any sample-size values based on that illustration are not the number of participants enrolled, not a justification reported by the sponsor, and not observed power. The registry record does not report the study’s own sample-size justification or analysis plan.

In general, power depends on the assumed effect, variability, design, analysis, and chosen significance level. A planning result is conditional on those inputs; it does not establish the probability that a completed study detected an effect. Because no primary endpoint analysis is recorded, an observed effect for that endpoint and its uncertainty are not available in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, but contains no analysis records. It does not report which outcomes were included in a formal analysis, how outcomes were prioritized beyond the designation of a primary endpoint, or whether any multiplicity procedure was planned. Multiplicity is a general concern when several outcomes or comparisons are tested: the more tests conducted, the greater the chance of at least one nominally unusual result under a collection of null hypotheses. The record does not give enough information to assess whether this issue arose or how it was handled.

Missing-data methods are not reported in the registry record. It does not describe participant withdrawals, incomplete follow-up, missing event information, censoring, imputation, or sensitivity analyses. These details matter because the amount and pattern of missing observation can affect safety summaries and event counts. Without them, the completeness of follow-up through the stated timeframe cannot be assessed from the registry entry.

The analysis population for the primary outcome is not reported in the registry record. The outcome population field is blank, and there is no analysis record specifying how participants were included or handled. General analysis-population choices can affect which observations contribute to a result, but no particular approach can be attributed to this study from the recorded information.

The record also does not describe interim analyses, stopping rules, or adjustments to statistical thresholds. These points are not assumptions to fill in: their status is simply not reported in the registry record. Consequently, no claim about multiplicity control, missing-data handling, or analysis populations can be made from the posted registry information.

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: amyotrophic lateral sclerosis (6.5%), dysphagia (3.2%), dyspnoea (2.7%), respiratory failure (2.7%), pneumonia (2.2%).

The registry lists 48 affected among 185 at risk for serious adverse events in the MT-1186 group. For other adverse events, it lists 123 affected among 185 at risk. It also records 12 deaths. These are separate entries in the registry record; they should not be added together or assumed to represent mutually exclusive groups. The record does not clarify overlap or provide a causal assessment.

The serious-event terms listed with percentages are Amyotrophic lateral sclerosis, 6.5%; Dysphagia, 3.2%; Dyspnoea, 2.7%; Respiratory failure, 2.7%; Pneumonia, 2.2%; and Weight decreased, 1.1%. The record does not specify the denominator for these percentages or whether each term represents people, events, or another reporting unit. The list should not be interpreted as exhaustive.

Seriousness and treatment relatedness are different concepts. The registry provides serious-event counts and terms, but does not state whether events were considered caused by MT-1186. The deaths entry likewise gives no cause or attribution. These figures describe what the registry records; they do not establish why events occurred or how the counts compare with another treatment.

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

The posted results give a descriptive account of safety entries for the MT-1186 group in a completed, single-group Phase 3 study. They record affected-person counts for serious and other adverse events, a deaths count, and a set of serious adverse-event terms with reported percentages. These figures are useful for understanding what the registry lists for this group during the study.

They do not establish a treatment effect relative to an untreated group or another intervention. The design has no randomized comparator, and the registry contains no outcome analysis records. Accordingly, the counts do not show whether event frequency changed because of MT-1186, nor do they provide a comparative estimate of the safety profile.

The primary outcome is an event count through up to 48 weeks, but no endpoint result or statistical analysis is reported. The registry also leaves the endpoint description, outcome population, and arm description blank. Without a precise event definition and analysis details, it is not possible to determine how the primary endpoint was operationalized or how its result should be interpreted.

The safety entries do not identify treatment attribution, event timing, or the causes of deaths. Nor does the registry explain the denominators for the listed term-specific percentages. These limitations mean the figures should be read as recorded descriptive summaries, not as proof that events were caused by treatment or that their frequency is greater or smaller than under another condition.

In general, a safety record can document observed events without resolving causality. Causal interpretation requires a suitable comparison and careful attention to outcome definition, follow-up, and analysis. The registry information supports a limited account of reported events in this group; it does not support a broader conclusion about comparative safety or efficacy.

13. Why This Trial Matters Statistically

Safety studies often produce several kinds of summaries: numbers of events, numbers of people affected, serious-event classifications, and deaths. These quantities answer different questions. Keeping them distinct is important, especially when the primary outcome is described as an event count while the safety entries also report affected-person counts. The registry record does not explain how these measures relate, making careful wording essential.

The study also illustrates the limits of interpreting single-group results. Descriptive counts can document the events recorded during a study, but they cannot by themselves distinguish treatment effects from the underlying condition, other care, or other circumstances. A comparator is what permits a direct between-group estimate under the study design; this record has none. The lack of a control should shape any interpretation of the safety figures.

Statistical precision is another important part of reporting. The registry does not provide a primary endpoint estimate, uncertainty interval, or analysis method. Without these, readers cannot assess the statistical uncertainty around the primary count from the registry record. General statistical concepts such as confidence intervals and over-dispersion matter for event-count analyses, but the record does not say whether those methods or checks were used.

Finally, the entry distinguishes a study’s stated objective from the results it reports. The objective concerns long-term safety and tolerability over 24 and 48 weeks, while the primary outcome has a timeframe of up to 48 weeks. The registry records safety counts, but does not report a formal analysis of the primary endpoint. Recognizing that distinction helps prevent descriptive entries from being overstated as a complete statistical evaluation.

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 registry record leaves several details necessary for interpreting the safety findings unspecified. The primary endpoint description and population are blank, and the outcome title’s wording does not define which events qualify or how recurrent events are counted. The record also does not explain how the event-count endpoint relates to the affected-person summaries listed for serious and other adverse events.

The study has no comparator group and no masking. As a result, the posted counts cannot provide a controlled estimate of relative event frequency, while the absence of masking may matter in general for event recognition or reporting. The record does not provide enough information to determine how events were collected or assessed.

There is no analysis record, and no endpoint estimate, confidence interval, or hypothesis test is reported. Statistical methods, the sample-size justification, and interim analyses are not reported in the registry record. Missing-data handling and analysis-population definitions are also absent. These omissions limit assessment of precision, completeness, and the way participants or events contributed to any result.

For the serious-event percentages, the denominator and reporting unit are not stated. The record does not clarify whether terms can overlap or whether the list is exhaustive. It gives no event attribution, timing, duration, or cause of death. Therefore, neither the listed terms nor the deaths count can be interpreted as treatment-caused outcomes from this record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety Study of Oral Edaravone Administered in Subjects With ALS — NCT04165824.
• Registry record last updated 2026-07-21; status last verified 2026-06.
• Results first posted 2022-08-29.
• 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

The registry identifies NCT04165824 as “Safety Study of Oral Edaravone Administered in Subjects With ALS,” sponsored by Shionogi. It records a completed Phase 3, single-group study of MT-1186 in ALS, with enrollment of 185, no masking, and allocation listed as not applicable. The study start date is 2019-11-18, and the primary completion date is 2021-10-07.

The stated objective is to evaluate long-term safety and tolerability over 24 and 48 weeks. The primary outcome is titled “Number of Treatment Emergency Adverse Events,” measured in events through up to 48 weeks. The record also lists four outcome measures and safety summaries for serious adverse events, other adverse events, deaths, and serious-event terms.

No outcome analysis records are included. The registry does not report the primary endpoint result, an analysis method, or a comparator-based estimate. The safety figures should therefore be read as descriptive entries for the MT-1186 group, with the endpoint-definition and analysis details absent from the registry record.