Study of Oral Edaravone in Healthy Adult Males: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Oral Edaravone in Healthy Adult Males (NCT04481750), a randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs).

2. Clinical Question

3. Trial Design

This was a Phase I randomized, single-blind, parallel study of MT-1186 and matching placebo in healthy adult males. Its stated purpose was to evaluate pharmacokinetics, safety, and tolerability with single and multiple doses of edaravone solution and suspension. The registry marks the trial completed and records enrollment of 74.

The study had two parts. Part 1 evaluated single doses and included cohorts described as S1 through S7 in the arm descriptions. The primary endpoint description says the single-dose study included 8 cohorts, with 56 subjects: 42 (6x7) receiving MT-1186 and 14 (2x7) receiving placebo. Part 2 evaluated multiple doses in cohorts M1 and M2. The primary endpoint description gives 18 subjects in this part, with 12 (6x2) receiving MT-1186. The available description does not state the placebo allocation for Part 2 in that breakdown.

The cohort structure matters when reading the safety counts. They are presented separately by cohort and by placebo group, rather than as one pooled result for all participants assigned to MT-1186 and one pooled placebo result. The single-dose record includes both Japanese and Caucasian male subjects, while the multiple-dose cohorts are described as Japanese male subjects. The registry does not report the dose amounts, the rationale for cohort sizes, or details of how randomization was implemented.

The study began on 2018-03-20 and reached primary completion on 2018-08-03. The registry record does not provide further information about follow-up beyond the stated endpoint timeframes or about the conduct of individual study visits.

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.

Only the first 6 of 11 groups are shown.

Period 1 (Fasted)

Reasons for not completing this period:

Period 2 (After Meal)

Analysis population for the primary outcome, as defined in the registry: The trial is divided into 2 phases (a single and multiple-dose). A single-dose study included 8 cohorts (total of 56 subjects), with 42 (6x7) subjects receiving MT-1186, and 14 (2x7) receiving the placebo. Multiple-dose study included 2 cohorts (total of 18 subjects), with 12 (6x2) receiving MT-1186, and 6 (3x2) receiving the placebo for 5 days. Since Cohort S3-1 and S3-2 are crossover cohort, the 5 subjects in Cohort S3-2 are overlapped (total of 79 subjects).

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.

Only the first 6 of 12 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs), measured over Day 1 to 8 in Part 1, up to 12 days in Part 2.

The primary endpoint counts participants with adverse events and adverse drug reactions. A participant count answers how many people in a reported group experienced an event, rather than how many separate event episodes occurred. The endpoint title combines adverse events and adverse drug reactions, while the posted safety fields distinguish serious adverse events from other adverse events. The registry does not give an operational definition of these categories in the information available for this analysis.

Safety and tolerability are central concerns in an early-phase study of single and multiple dosing. Recording participants affected can reveal whether events were reported during the specified observation period and can help describe the kinds of safety information collected. The endpoint is assessed from Day 1 to 8 in Part 1 and up to 12 days in Part 2, so the observation window differs by study part.

The posted values are cohort-level counts, with separate entries for MT-1186 and matching placebo groups. These counts describe what was recorded in each group; they are not, by themselves, an adjusted comparison or a test of whether the groups differ. The registry also lists changes from baseline in heart rate, PR interval, QTcF interval, and QRS duration as secondary outcomes. Those ECG-related outcomes are distinct from the primary adverse-event count.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a binary participant-level measure: whether a participant was counted as experiencing an event. Binary outcomes classify each participant into event or no-event status for the defined endpoint. The posted values are counts of affected participants and participants at risk in each cohort entry. They are not event rates calculated across the study, and the registry does not supply an overall treatment effect for this endpoint.

What does a participant count tell us?

A participant count is a direct description of the number recorded with an event. It does not reveal how many episodes each affected participant experienced, how severe events were unless severity is separately defined, or how events were distributed over time. The registry separately lists serious events and other events, but the available record does not define the event coding rules, whether one participant could appear in more than one category, or how adverse drug reactions were distinguished from adverse events.

The at-risk counts provide the group sizes associated with the posted affected counts. They should be read within their stated cohort entries. The primary outcome description also gives study-part group breakdowns, but the cohort safety data are not presented as one overall comparison. No new combined counts or event proportions should be inferred from these entries.

Why do the cohorts matter?

Randomization can support a fair comparison when the groups being compared come from the same randomized contrast and the analysis respects the design. Here, the registry presents multiple single-dose cohorts and multiple-dose cohorts separately, alongside placebo entries for each study part. The information available does not specify a single primary contrast, explain whether all dose cohorts were intended to be combined, or describe any adjustment for cohort or dose. A reader should therefore distinguish the reported within-cohort counts from a treatment effect estimate.

The trial is marked randomized, single-blind, and parallel. These design labels indicate that assignment was randomized, masking was single, and participants were allocated to parallel groups rather than crossing between treatments, as recorded by the registry. They do not, without further details, establish the sequence-generation method, concealment procedures, identity of the masked party, or whether masking remained effective.

How should uncertainty be understood?

General explanation: a confidence interval is a range of values compatible with the observed data under a specified statistical method. It communicates uncertainty about an estimated effect, rather than merely whether an observed count is large or small. No confidence intervals or effect estimates are reported for this endpoint, so precision of a treatment-placebo difference cannot be assessed from the registry record.

General explanation: formal tests also depend on a clearly defined comparison, an analysis population, and assumptions about the data. The record lists 0 analyses. It does not report a test statistic, p-value, or adjustment for the cohort structure. In the absence of those details, the cohort-level counts should be treated as descriptive rather than as evidence from a reported inferential comparison.

What does the planning illustration represent?

The statistical planning illustration is based on the observed effect and states assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Its effect to detect is a stated fraction of the observed effect. Such planning quantities are hypothetical illustrations of sample size under their assumptions, not observed trial results and not observed power. The record does not report that these assumptions were used to design this trial, and the numerical planning outputs should not be interpreted as the trial’s original sample-size justification.

General explanation: sample-size calculations depend on the target effect, outcome variability or event frequency, allocation, significance criterion, and analysis method. Changing any of these assumptions can change the planning result. For binary outcomes, sparse event counts can make normal approximations less dependable; the registry’s planning description nevertheless specifies a normal approximation for the illustration. It does not report a separate method for handling sparse counts.

The record does not describe interim analyses, a detailed statistical analysis plan, covariate adjustment, multiplicity control, or methods for missing outcome data. Those methods cannot be inferred from the fact that the trial was randomized or from the observed counts. In particular, the 0 analyses listed should not be replaced by an assumed test or reconstructed analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary adverse-event and adverse-drug-reaction endpoint and 24 outcome measures. Secondary outcomes include change from baseline in heart rate, PR interval, QTcF interval, and QRS duration. The available record does not state how many outcomes were designated primary for statistical testing beyond the named primary endpoint, how the secondary outcomes were ordered, or whether any adjustment for multiple comparisons was planned or performed. It also lists 0 analyses, so there are no posted inferential results from which to assess multiplicity handling.

Missing-data methods are not reported in the registry record. The available information does not say whether all randomized participants were included in each outcome analysis, how missing assessments were handled, or whether participants who did not complete a planned observation period were excluded or retained. The at-risk counts in the adverse-event entries identify the denominators shown for those entries, but do not explain whether any missing information or withdrawals affected those denominators.

Analysis populations are also not reported in sufficient detail. The record does not define safety, pharmacokinetic, or other analysis sets, nor does it specify whether analyses followed randomized assignment. Without those definitions, the count entries can be described as posted group results, but cannot be assigned to an assumed analysis population or used to infer how missing data were treated.

General explanation: multiplicity arises when several outcomes, time points, or comparisons are assessed. Without a stated plan, readers cannot know whether the interpretation of any individual test accounts for the overall number of opportunities to find a result. No such tests are reported, so no multiplicity-adjusted statistical conclusion can be drawn.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event fields show zero affected participants in each listed MT-1186 cohort and each matching-placebo group. The deaths field is also zero for every listed group. These are the recorded counts during the specified study periods; they are not evidence that the risk is exactly zero beyond the participants and observation windows represented in the record.

The other-adverse-event fields report affected participants separately by cohort. The single-dose MT-1186 entries range across the posted counts of 0, 2, 3, 0, 1, 1, and 2, with 2 in the single-dose placebo entry. In the multiple-dose part, the MT-1186 entries are 2 and 1, and the placebo entry is 1. These are group counts, not estimates adjusted for cohort, dose, or time.

General explanation: serious and non-serious categories describe different aspects of safety reporting; a zero count for serious events does not mean there were no other adverse events. The record does not provide event descriptions, severity grades, causal assessments, or participant-level details. Counts should therefore be read as a limited summary of reported safety observations, not as a complete characterization of the nature or duration of events.

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

The results describe a Phase I study in healthy adult males that assessed single and multiple dosing of MT-1186, with matching placebo groups. For the posted safety outcome, serious adverse-event counts and death counts are zero in every listed group, while other adverse-event counts are reported by cohort. This provides a descriptive account of the events recorded during the specified study periods.

The counts do not establish whether MT-1186 caused an event, whether an event was related to treatment, or whether the frequency differed meaningfully from placebo. Although the primary endpoint title includes adverse drug reactions, the available fields do not explain how relatedness was assessed. There is no reported treatment-placebo effect estimate, confidence interval, or formal test for the primary endpoint. A numerical comparison between separate cohort counts would not, on its own, resolve these questions.

The study’s population also limits the scope of interpretation. The registry describes healthy adult males, including Japanese and Caucasian subjects in the stated cohorts. The results are not a direct account of outcomes in patients with a disease. The posted safety counts also do not answer the pharmacokinetic questions named in the study purpose, because pharmacokinetic results are not included in the information available for this analysis.

General explanation: early-phase studies commonly contribute information about exposure, tolerability, and safety under the tested conditions. That role is different from demonstrating a clinical benefit or establishing the balance of benefits and harms in a patient population. This record’s posted endpoint is a safety count, not a measure of therapeutic benefit.

The results should therefore be read narrowly: they report cohort-specific event counts from the registry record and leave substantial questions about comparative precision, event details, and broader applicability unresolved. They neither establish that treatment works nor show that it does not work.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why design labels, outcome counts, and comparative evidence are not interchangeable. The registry identifies randomization, single masking, and a parallel design, but the outcome data are reported across several dose cohorts rather than as one defined treatment-placebo estimate. The cohort structure is essential context for interpreting the raw counts.

It also illustrates a distinction between a participant-level binary outcome and an inferential result. Counts show how many participants were recorded with events in each entry; they do not give uncertainty around a treatment contrast. With no analyses listed and no confidence intervals or tests reported, readers cannot judge the precision of a comparative effect from the record.

The study further highlights how the meaning of a zero count depends on observation and reporting. Every listed group has zero serious adverse events and zero deaths, but the endpoint timeframes are limited and the registry gives no event-level descriptions in the information available. A zero observed count is a description of the record, not proof that an event cannot occur.

Finally, planning illustrations based on observed effects should not be confused with design documentation. The stated assumptions describe a hypothetical calculation and do not establish the trial’s original sample-size rationale. Keeping design assumptions, observed results, and statistical uncertainty separate is important when reading early-phase registry data.

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 trial-specific uncertainties. The primary outcome description refers to 8 single-dose cohorts, while the arm descriptions list S1 through S7 and the safety data label the S3 entry without the S3-1 and S3-2 labels used in the arm descriptions. The record does not explain this naming or cohort mapping. This complicates interpretation of how the listed safety entries correspond to the complete arm structure.

The primary outcome description reports group breakdowns for the study parts, but the posted safety results remain cohort-level. The available information does not define a pooled comparison across dose cohorts, nor does it provide a formal analysis that accounts for dose or cohort. The placebo allocation is described in the single-dose breakdown and appears in separate safety entries for both study parts, but the multiple-dose allocation is not specified in the primary population breakdown.

The record does not state dose amounts in the information, explain the allocation procedure beyond labeling the study randomized, or identify who was masked. It does not provide operational definitions for adverse events, adverse drug reactions, or serious events, nor does it provide event descriptions, severity, timing, or relatedness assessments.

In addition, analysis populations, missing-data handling, multiplicity procedures, interim analyses, and a detailed statistical plan are not reported in the registry record. No inferential analyses are listed. The results therefore offer limited descriptive safety information and do not support a precise comparative interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Oral Edaravone in Healthy Adult Males — NCT04481750.
• Registry record last updated 2026-07-16; status last verified 2026-06.
• Results first posted 2024-08-02.
• 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.

18. Record Summary

The registry identifies NCT04481750 as a completed randomized, single-blind, parallel Phase I study titled “Study of Oral Edaravone in Healthy Adult Males.” It records enrollment of 74 and describes single-dose and multiple-dose parts comparing MT-1186 with matching placebo in healthy adult males. The study’s stated purpose was to evaluate pharmacokinetics, safety, and tolerability of single and multiple doses of edaravone solution and suspension.

The primary outcome counts participants with adverse events and adverse drug reactions, with a timeframe of Day 1 to 8 in Part 1 and up to 12 days in Part 2. Serious adverse-event and death counts are zero in every listed group; other adverse events are reported by cohort. The record lists ECG-related secondary outcomes, 24 outcome measures, and 0 analyses. It does not report a formal comparative effect estimate or the statistical and missing-data methods needed to interpret one.