Clinical Pharmacology Study of Oral Edaravone in Patients With Amyotrophic Lateral Sclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Pharmacology Study of Oral Edaravone in Patients With Amyotrophic Lateral Sclerosis (NCT04176224), a na phase 1 study. The primary outcome is Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Quantifiable Concentration Time-point (AUC0-t) of Unchanged Edaravone.

2. Clinical Question

In general, a pharmacokinetic study describes how a drug concentration changes in the body over time. This question is different from asking whether a treatment changes ALS symptoms or disease progression. The registry record names a secondary outcome concerning participants with adverse events and adverse drug reactions, but it does not report a clinical efficacy endpoint.

3. Trial Design

This was a completed Phase 1, single-group clinical pharmacology study sponsored by Shionogi. The registry record identifies Japanese patients with ALS as the condition and lists 9 participants as enrolled. The study began on 2019-04-17, and primary completion was recorded as 2019-09-04.

Participants received MT-1186, described as edaravone oral suspension. The brief study summary says the objective was to evaluate pharmacokinetics of single doses. The registry record describes no separate control arm, records allocation as NA, and lists masking as none. These features mean the design is not a randomized comparison and the group is not a like-for-like control for another treatment.

The primary outcome was the mean area under the plasma concentration-versus-time curve for unchanged edaravone, from time zero to the last quantifiable concentration. Its stated unit is ng·h/mL, and the listed dispersion measure is standard deviation. Plasma collection was scheduled at pre-dose and at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours on Day 1, and at 24 hours after administration on Day 2.

The registry record lists 13 outcome measures and a secondary outcome concerning the number of participants with adverse events and adverse drug reactions. It lists 0 analyses. The protocol details, including the full analysis plan, eligibility criteria, and justification for enrollment, are not reported in the registry record. The record does not provide a numerical primary endpoint result.

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

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 Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Quantifiable Concentration Time-point (AUC0-t) of Unchanged Edaravone, measured over Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration..

The primary endpoint is the area under the plasma concentration-versus-time curve from time zero to the last quantifiable concentration (AUC0-t) for unchanged edaravone. It is expressed in ng·h/mL, with the mean and standard deviation specified as summary measures. The registry record describes plasma sampling from pre-dose through 12 hours on Day 1 and again at 24 hours after administration on Day 2.

In general, an area under a concentration-time curve summarizes measured drug exposure across the observation interval. It combines information from concentrations at multiple sampling times rather than representing a single concentration measurement. The interval matters: AUC0-t ends at the last quantifiable concentration, so it should not be treated as exposure over an unlimited period or automatically equated with a different AUC definition.

Pharmacokinetic endpoints such as AUC are used to characterize drug exposure. They answer a different question from clinical outcomes, such as changes in symptoms or function. The stated endpoint concerns unchanged edaravone in plasma; it does not itself measure clinical benefit or disease progression.

The registry record names the endpoint and its summary measures but does not report the observed mean, standard deviation, or number of participants contributing to the endpoint. The primary numerical result is therefore not reported in the registry record. Without those values, the magnitude and precision of the observed exposure cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The recorded primary measure is a continuous pharmacokinetic endpoint: AUC0-t for unchanged edaravone, with the unit ng·h/mL. The registry record specifies the mean as the parameter and standard deviation as the dispersion measure. It does not report the observed mean or standard deviation, nor does it provide a confidence interval, test statistic, or p-value for the primary endpoint.

What does the endpoint summarize?

In general, an area under a concentration-time curve summarizes exposure over a defined observation interval. The concentration measurements collected at scheduled times describe a curve; the area under that curve captures the accumulated concentration over the interval. Here, the stated endpoint runs from time zero to the last quantifiable concentration. It is important to retain that endpoint definition rather than assume that it covers a different interval.

The recorded schedule includes pre-dose and multiple post-dose samples on Day 1, followed by a sample at 24 hours after administration on Day 2. In general, repeated concentration measurements help characterize the course of plasma concentrations over time. The record does not report the actual concentrations, the participant-level curves, how the last quantifiable time point was determined, or the numerical AUC values.

What do mean and standard deviation communicate?

In general, the mean describes the average of observed values, while the standard deviation describes how dispersed individual values are around that average. They serve different purposes: the mean summarizes location, and the standard deviation summarizes variability among observations. Neither is available numerically for the primary endpoint in the registry record. A standard deviation is not a confidence interval; it describes variation in the observations rather than directly giving the precision of the estimated mean.

In general, a confidence interval can express uncertainty around an estimate, subject to the statistical model and data assumptions. A narrower interval generally indicates greater precision than a wider one. No confidence interval for AUC0-t is reported in the registry record, and no alternative uncertainty interval is identified. Precision therefore cannot be judged from the posted primary endpoint information.

What can be inferred from the design?

The record describes a single-group study with allocation recorded as NA and masking as none. In general, a single-group pharmacokinetic study can characterize measurements in the participants studied, but it does not create a concurrent control group for a treatment contrast. This design is consistent with a clinical pharmacology objective, but it does not establish a comparative treatment effect. The study is listed as Phase 1 and the brief summary describes evaluation of pharmacokinetics after single doses.

The registry record lists 9 enrolled participants and 0 analyses. It does not identify the number with complete primary endpoint data, the analysis population, or the method used to derive AUC0-t. Those details are relevant to understanding how participant measurements became a group summary. They are not reported in the registry record, so no assumptions should be made about handling of incomplete measurements or the analysis procedure.

How should planning calculations be understood?

In general, a sample-size planning illustration asks how many participants might be needed under specified assumptions to detect a chosen effect with a chosen statistical power. Such an illustration is not an observed result and is not observed power. The registry record describes planning assumptions based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It also distinguishes total events for time-to-event calculations from participants per arm for other calculations.

Those planning assumptions do not describe the actual single-group design, which has no two-arm randomized comparison. The planning figures are not results from this study, and they should not be interpreted as evidence about the study's precision or success. No numerical planning outputs are stated in the registry record details used for this account. More importantly, planning calculations cannot substitute for the missing numerical AUC0-t result.

In general, over-dispersion means that observed variation exceeds what a statistical model assumes. It can affect standard errors and the reliability of inferential results. The registry record does not report an over-dispersion assessment or a model for the primary endpoint. No claim about such an assessment can be made for this study.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("MT-1186")
n   <- c(9)
m   <- c(1719)
sp  <- c(808)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  MT-1186  9  1719.000  808.000  1097.916  2340.084

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures, including the primary pharmacokinetic endpoint and a secondary outcome concerning participants with adverse events and adverse drug reactions. It also lists 0 analyses. A statistical plan describing how multiple outcomes were handled, whether any adjustments were planned, or which analyses were considered confirmatory is not reported in the registry record.

In general, evaluating multiple outcomes can raise the chance of finding an apparently notable result by chance when many statistical tests are performed. A multiplicity plan explains how interpretation or testing accounts for that issue. The number of listed outcome measures alone does not establish that separate hypothesis tests were performed, and no such tests are reported in the registry record. No adjustment should be presumed.

The record does not report missing-data counts, reasons for missingness, or a method for handling incomplete plasma measurements. It does not identify an analysis population or state how many participants contributed to the primary endpoint. These omissions limit assessment of whether the endpoint summary represents all enrolled participants or a subset with available measurements. The scheduled plasma collection times are recorded, but a schedule does not establish that every sample was collected or quantifiable.

In general, missing measurements can affect the estimate and its precision, depending on their amount and pattern. Without reported missingness and analysis details, the direction or size of any such effect cannot be assessed. The record also does not report a statistical analysis plan, interim analyses, or a sample-size justification. Those elements are not reported in the registry record and should not be inferred from the enrollment or the general planning assumptions.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports 0 participants with serious adverse events among 9 at risk. It reports 1 participant with other adverse events among 9 at risk and 0 deaths. No serious adverse event terms are listed. The secondary outcome is described as the number of participants with adverse events and adverse drug reactions, but a separate count for adverse drug reactions is not reported in the registry record.

These are participant counts, not event rates calculated. The record does not provide a comparison group, so the counts cannot be used to compare risks against another treatment or no treatment. The absence of a reported serious adverse event in this group does not establish that serious events are impossible or that the treatment has no safety risks. Likewise, the count for other adverse events does not by itself establish causation.

In general, safety interpretation depends on the definitions used, the duration and completeness of follow-up, event severity and type, and how events were attributed. Those details are not reported in the registry record. The posted figures should therefore be read as the recorded counts for this small single-group study, not as a comprehensive estimate of safety.

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

This study addresses a pharmacokinetic question: the registry record specifies measurement of AUC0-t for unchanged edaravone after administration of oral suspension to Japanese patients with ALS. It records an enrollment of 9 and a schedule of plasma collections through 24 hours after administration. However, the numerical primary endpoint result is not reported in the registry record. The magnitude and variability of plasma exposure therefore cannot be described from the posted result information.

The design is single-group, with no separate comparator. It can be understood as a clinical pharmacology study, but it does not provide a randomized comparison with another treatment or a control condition. The record does not report an efficacy endpoint or a clinical outcome result. The pharmacokinetic objective should not be mistaken for a test of symptom improvement, disease progression, or treatment effectiveness.

The safety record lists 0 participants with serious adverse events among 9 at risk, 1 participant with other adverse events among 9 at risk, and 0 deaths. These descriptive counts are limited to what is recorded; they do not show whether an event was caused by the intervention, and there is no comparator group for context. Serious event terms and further details about safety follow-up are not reported in the registry record.

In general, a study result needs both an estimate and information about its uncertainty to support a clear assessment of magnitude and precision. The registry record does not report the primary mean, standard deviation, or confidence interval. It is therefore not possible to assess how precise the estimated exposure would be, even if a numerical estimate were available elsewhere. The record's missing numerical endpoint result should not be interpreted as a value of zero or as proof that measurements were not made.

The information supports a description of the study question, design, sampling schedule, enrollment, and recorded adverse-event counts. It does not support a conclusion about clinical benefit or lack of benefit, a comparative treatment effect, or a complete safety profile. Those conclusions would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates the distinction between pharmacokinetic evidence and clinical efficacy evidence. Its primary endpoint concerns plasma exposure to unchanged edaravone, summarized as AUC0-t. That measure can characterize drug concentrations over a defined time interval, but it does not directly measure ALS symptoms or disease progression. Keeping the endpoint aligned with the study question prevents exposure measures from being overinterpreted as clinical outcomes.

The study also illustrates why design context matters. The record lists a single group, allocation as NA, and no masking. There is no like-for-like control group, so the study is not a randomized treatment comparison. Its Phase 1 designation and stated clinical pharmacology objective describe its role, but the registry record does not report a numerical primary result or an analysis plan from which to assess the endpoint estimate.

Precision is central to interpreting a continuous pharmacokinetic measure. A mean and standard deviation are specified, but their values are not reported in the registry record, nor is a confidence interval. Without those quantities, readers cannot judge the observed level of exposure or its variability. Enrollment of 9 provides scale, but does not establish how many participants contributed to the primary endpoint.

The safety counts offer another useful statistical distinction: a count observed in a single group is descriptive, not a comparative risk estimate. The recorded serious-event count is 0 among 9 at risk, while 1 participant among 9 at risk had other adverse events and the death count is 0. These observations do not establish comparative safety or causality.

Finally, registry transparency depends not only on naming outcomes but also on posting results and analysis details. The record lists 13 outcome measures and 0 analyses, while the numerical primary endpoint result is not reported in the registry record. This limits reproducibility and prevents a quantitative assessment of the main pharmacokinetic finding.

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 main limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. Although the endpoint definition, unit, summary parameter, dispersion measure, and plasma collection schedule are listed, the observed mean and standard deviation are not. No confidence interval or numerical analysis result is reported, so the endpoint magnitude and precision cannot be evaluated.

The study enrolled 9 participants and used a single-group design. Allocation is recorded as NA, masking as none, and there is no separate comparator. Consequently, the record does not support a controlled comparison. The number of enrolled participants does not establish how many had complete or quantifiable plasma samples, and the endpoint analysis population is not reported in the registry record.

Further details needed to assess the endpoint are not reported in the registry record, including the statistical analysis method, handling of missing measurements, participant characteristics, and the method used to derive AUC0-t. The record lists 13 outcome measures and 0 analyses, but a multiplicity approach and a statistical analysis plan are not reported. The sample-size justification and any interim analyses are also not reported in the registry record.

Safety interpretation is limited to the listed counts: 0 participants with serious adverse events among 9 at risk, 1 with other adverse events among 9 at risk, and 0 deaths. Serious event terms, event details, and further follow-up information are not reported in the registry record. With no comparator, these counts do not establish causal attribution or comparative risk. These limitations restrict the conclusions to the recorded study design and descriptive information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Pharmacology Study of Oral Edaravone in Patients With Amyotrophic Lateral Sclerosis — NCT04176224.
• Registry record last updated 2026-07-15; status last verified 2026-06.
• Results first posted 2024-01-24.
• 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

This completed Phase 1 study evaluated the pharmacokinetics of single doses of edaravone oral suspension, identified as MT-1186, in Japanese patients with ALS. Shionogi is listed as the sponsor. Enrollment was 9; the study began on 2019-04-17, and primary completion was recorded as 2019-09-04.

The study was single-group, with allocation recorded as NA and masking as none. The primary endpoint was mean AUC0-t for unchanged edaravone, in ng·h/mL, with standard deviation specified as the dispersion measure. Plasma collection was scheduled on Day 1 through 12 hours and at 24 hours after administration on Day 2. The numerical primary endpoint result is not reported in the registry record, which lists 0 analyses.

The record lists 13 outcome measures and a secondary outcome concerning adverse events and adverse drug reactions. It reports 0 participants with serious adverse events among 9 at risk, 1 participant with other adverse events among 9 at risk, and 0 deaths. No serious adverse event terms are listed. The design and posted information support description of the clinical pharmacology question and recorded safety counts, but do not provide a comparative treatment effect or a clinical efficacy result.