A Study of Intravenous Perampanel in Japanese Participants With Epilepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Intravenous Perampanel in Japanese Participants With Epilepsy (NCT03754582), a na phase 2 study. The primary outcome is Number of Participants With Serious Adverse Events (SAEs).

2. Clinical Question

The question is primarily about safety and tolerability during a switch from oral tablets to intravenous infusion, rather than about comparative efficacy. The record also lists seizure frequency and plasma concentration as secondary outcomes, but numerical results for those measures are not reported in the registry record.

Because the study has no concurrent control group, its observed events describe what occurred among participants during the different phases. They do not estimate how those same participants would have fared under a separate treatment or control condition. The phase-specific counts can provide descriptive context, but the treatment phase cannot be isolated from changes over time, the treatment sequence, or other factors using this design alone.

3. Trial Design

This completed phase 2 study is described as a multicenter, uncontrolled, open-label study in Japanese participants with epilepsy. The registry lists a single-group model, no masking, and no randomized allocation. Enrollment was 21. The study started on 2018-11-27, and primary completion was 2019-12-10.

The planned treatment sequence began with oral perampanel at 8 to 12 mg once daily during a pretreatment phase lasting 28 days, identified as Day -28 to Day -1. Participants were then switched to perampanel given by intravenous infusion over 30 minutes. The registry describes the treatment phase as lasting up to 4 days. An oral perampanel follow-up phase followed, lasting up to 28 days after the last dose. The overall serious adverse event timeframe is stated as up to 60 days.

The same 21 participants are listed as at risk in each phase-specific adverse event group. This is a within-study sequence, not a set of independent, randomized arms. The registry does not describe a concurrent comparator, and the different phases should not be treated as if they were like-for-like control groups. In particular, participants were not allocated to receive oral or intravenous perampanel in parallel groups.

The registry describes the study purpose as evaluating safety and tolerability when intravenous perampanel is used as a substitute for oral tablets, as adjunctive therapy. The named seizure groups are partial onset seizures, including secondarily generalized seizures, and primary generalized tonic-clonic seizures. Specific details beyond the listed study description, including the rationale for the chosen study design or the justification for enrollment, are not reported in the registry record.

Open-label means that the study is not described as masked; the record lists masking as none. The treatment sequence and phase descriptions allow the event counts to be read in context, but the design does not support a randomized causal comparison between routes of administration. The study status is completed.

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 27 participants were consented, of which 6 were screen failures and 21 were enrolled and received the study treatment.

Pretreatment Phase

Treatment Phase

Reasons for not completing this period:

Follow-up Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of study drug.

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: All participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Serious Adverse Events (SAEs), measured over Up to 60 days (Pretreatment Phase: up to 28 days, Treatment Phase: up to 4 days, Follow-up Phase: up to 28 days after last dose).

The primary endpoint is the number of participants with serious adverse events. It is a participant count: it records whether a participant experienced a serious event during the stated observation timeframe, rather than measuring event severity on a numerical scale or counting every occurrence as a separate participant.

The registry defines a serious adverse event as an untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolonged an existing hospitalization, resulted in persistent or significant disability or incapacity, or was a congenital anomaly or birth defect. The definition focuses on consequential outcomes, making this endpoint a way to describe serious safety events during the study.

The endpoint timeframe is up to 60 days, consisting of pretreatment up to 28 days, treatment up to 4 days, and follow-up up to 28 days after the last dose. The primary endpoint population is all participants who received at least 1 dose of study drug. The posted adverse event results break out serious events by phase: 0 participants in pretreatment, 1 in treatment, and 2 in follow-up. An overall count of unique participants across the full timeframe is not reported in the registry record.

As a general statistical point, participant counts are straightforward to interpret when the population and observation period are clear. They do not by themselves convey the timing, duration, recurrence, or clinical course of an event. Nor does a count establish that a treatment caused an event. Those interpretations require information and comparisons beyond the endpoint count alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting the results starts with distinguishing a count from a rate or a comparison. The primary endpoint counts participants who experienced at least one serious adverse event within the study timeframe. The phase-specific results give counts of participants with serious events and counts at risk for each phase. These are descriptive summaries: they report what was recorded, without estimating a treatment contrast.

What does a participant count tell us?

A participant count answers how many people in the listed group met the event definition. It is not the same as a count of all event episodes. If one person experienced multiple events, a participant-based endpoint can still count that person once for the endpoint. The registry labels the primary measure as a count of participants, but it does not provide event-level detail sufficient to reconstruct episodes or determine whether the same participant appears in more than one phase.

The distinction matters for reading the three phase counts. The 0, 1, and 2 participants are reported separately for pretreatment, treatment, and follow-up. They should not be summed to infer the number of unique participants with an event across the full timeframe, because participant overlap across phases is not specified. The overall number of unique participants with serious adverse events is not reported in the registry record.

Why does the design affect interpretation?

In general, a randomized comparison aims to make treatment groups comparable in expectation, so that differences in outcomes can be interpreted as evidence about the assigned treatments, subject to uncertainty and study conduct. This study is described as uncontrolled, open-label, and single group, with no randomized allocation. The intravenous phase follows oral pretreatment and precedes oral follow-up. Since route and study period change together, any difference in event counts across phases cannot isolate a route effect.

In general, a confidence interval expresses a range of values compatible with the data under a specified statistical method. It helps communicate uncertainty beyond a single estimate. No confidence interval for the serious adverse event results is reported in the registry record. No p-value or inferential comparison for the phase counts is reported either. The counts can be stated directly, but the precision of a population-level estimate cannot be characterized using an unreported interval.

How should sample-size illustrations be understood?

The record describes sample-size calculations as planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumed effect is a stated fraction of the observed effect. These calculations are not the trial's design description: the actual study is single group and uncontrolled, not a two-arm randomized comparison. The illustrations are hypothetical planning exercises, not evidence that the trial had a particular probability of detecting an effect. Sample sizes for a proposed study are planning quantities, not observed power.

General statistical principle: a planning calculation depends on the assumptions used, including the effect to detect, the significance level, the allocation, and the analysis approach. If those assumptions do not match the design of the completed study, the calculation should not be read as a direct description of what the study tested. The registry does not report the trial's own sample-size justification or explain a protocol-based power target.

What does multiplicity mean in this setting?

Multiplicity arises when several outcomes, time points, or statistical comparisons are examined. In general, conducting many tests can increase the chance of at least one apparently notable result arising by chance if no adjustment or interpretation plan is used. The registry lists secondary outcomes, including mean seizure frequency per day across phases and plasma concentration before and after switching. It does not report a multiplicity strategy, a hierarchy among outcomes, or results of those secondary measures. The record lists no analysis records, which does not establish that no analyses were conducted; the statistical analysis details are not reported in the registry record.

What is known about analysis populations?

The primary endpoint population is defined as all participants who received at least 1 dose of study drug. The record reports 21 enrolled participants and 21 at risk in each phase-specific adverse event group. It does not describe other analysis populations or state how participants with incomplete observations were handled. This definition is useful because it identifies who was intended to contribute to the primary endpoint, but it does not show whether every participant completed every phase.

Missing data can affect interpretation if participants do not have complete observation over the planned timeframe. General statistical principle: the consequences depend on why data are missing, how much information is missing, and the analysis approach. The registry does not describe missing-data methods or provide details about incomplete follow-up. It is therefore not possible to assess whether missing observations could have affected the event summaries.

Finally, event definitions and observation windows are part of the method, not just labels. The serious event definition focuses on specified consequential outcomes, and the timeframe spans pretreatment, treatment, and follow-up. The reported phase-specific counts are meaningful only in that context. They describe events meeting the stated definition during the listed periods; they do not measure every possible adverse symptom or establish causation.

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("Pretreatment Phase: Oral Perampanel 8 to 12 mg/Day", "Treatment Phase: Intravenous Perampanel 8 to 12 mg", "Follow-up Phase: Oral Perampanel 8 to 12 mg/Day")
n      <- c(21, 21, 21)
events <- c(0, 1, 2)
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  Pretreatment Phase: Oral Perampanel 8 to 12 mg/Day  21  0  0.0  0.0  16.1  -0.0  15.5  0.1  15.4
ARM  Treatment Phase: Intravenous Perampanel 8 to 12 mg  21  1  4.8  0.1  23.8  0.8  22.7  1.1  22.8
ARM  Follow-up Phase: Oral Perampanel 8 to 12 mg/Day  21  2  9.5  1.2  30.4  2.7  28.9  2.9  29.2

11. Multiplicity, Missing Data and Analysis Populations

The registry names the primary endpoint and describes the population for it as participants who received at least 1 dose of study drug. It also lists secondary outcomes concerning mean seizure frequency per day and plasma concentration before and after the switch to intravenous infusion. Numerical results for those secondary outcomes are not reported in the registry record.

A multiplicity strategy addresses how to interpret results when several outcomes or comparisons are examined. As a general statistical matter, a prespecified hierarchy or adjustment can help control the risk of chance findings across multiple tests. The registry does not report such a strategy, the order in which outcomes were tested, or inferential results for the listed secondary outcomes. No analysis records are listed; that does not establish that no analyses took place. The analysis methods are not reported in the registry record.

The primary endpoint population is stated, and 21 participants are listed at risk in each phase. However, the handling of missing observations, early discontinuation, or incomplete follow-up is not reported in the registry record. The record also does not describe other analysis populations or explain whether participants with missing data were excluded, retained, or handled by another method.

General statistical principle: missingness can matter when the likelihood of an unobserved outcome is related to a participant's condition or experience. Without information on completeness and the approach to missing data, the possible influence on results cannot be evaluated. The phase-specific counts remain descriptive of the posted observations, but they do not establish that all participants had complete observation throughout the full timeframe.

Similarly, an absent inferential method should not be replaced with an assumed one. No confidence interval, hypothesis test, or adjusted comparison for the serious adverse event counts is reported in the registry record. These limitations constrain precision and comparative interpretation, but do not change what the registry reports as the observed phase-specific counts.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypoaesthesia (4.8%), delusion (4.8%), loss of consciousness (4.8%).

The serious adverse event results are presented by study phase. The oral pretreatment phase lists 0 participants with serious adverse events out of 21 at risk; the intravenous treatment phase lists 1 out of 21; and the oral follow-up phase lists 2 out of 21. Each phase lists 0 deaths. The primary endpoint timeframe covers up to 60 days, including pretreatment, treatment, and follow-up.

These figures are counts of participants, not necessarily counts of individual event episodes. They are phase-specific and should not be added to estimate the number of unique participants with an event across the entire study, because the record does not state whether the same person had an event in more than one phase. An overall unique-participant count for the full timeframe is not reported in the registry record.

The serious event terms listed include Hypoaesthesia, Delusion, and Loss of consciousness, each reported at 4.8%. The registry information cited does not assign those terms to a particular phase or provide further detail about their timing or course. These terms and percentages should therefore be read as reported event listings, not as a comparison across phases.

General statistical principle: counts are informative descriptions of observed events, but they are not by themselves causal evidence. With no concurrent control group, the observed events cannot distinguish treatment-related effects from other explanations. The counts also do not convey the uncertainty around an underlying event frequency; no confidence intervals are reported in the registry record.

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

The results describe serious adverse events recorded during a sequential study of oral and intravenous perampanel. The phase-specific counts are 0 participants during oral pretreatment, 1 during intravenous treatment, and 2 during oral follow-up, with 21 participants at risk in each phase. No deaths are listed in any phase. The record also lists Hypoaesthesia, Delusion, and Loss of consciousness as serious event terms, each at 4.8%.

These observations do not establish that intravenous perampanel caused an event, or that the oral and intravenous routes differ in safety. There is no concurrent comparator, and the phases occur in sequence. The pretreatment and follow-up periods are not randomized control groups. Changes in counts across phases can be described, but they cannot be attributed to route alone on the basis of this design.

The figures also do not show how many unique participants had at least one serious adverse event across the whole study. The phase counts may not represent distinct people, and a full-timeframe unique-participant total is not reported in the registry record. Nor do the counts give event-level detail about timing, duration, recurrence, or outcome.

The study was designed to evaluate safety and tolerability in participants switching from oral tablets to intravenous infusion. The reported endpoint and phase-specific safety data address that descriptive purpose, but the record does not report numerical results for the listed seizure-frequency or plasma-concentration outcomes. No claim about changes in seizure control or drug concentration can be based on the posted serious event counts.

As a general statistical point, a result's meaning depends on both its estimate and its uncertainty. The registry reports counts but no confidence intervals or inferential comparison for the serious adverse events. The counts identify what was recorded in this study; they do not, alone, determine how precisely those findings apply beyond the observed participants.

The record does not report the rationale for its enrollment, a protocol-based sample-size justification, or detailed analysis methods. Planning illustrations, where presented, should be understood as hypothetical sample-size calculations rather than as evidence of observed power or a formal comparison within this single-group study. The most defensible reading is therefore descriptive: serious events were recorded in the treatment and follow-up phases, none in pretreatment, and the study design does not establish comparative or causal conclusions.

14. Why This Trial Matters Statistically

Statistically, this study illustrates why the design and the endpoint must be read together. A participant count for serious adverse events is a direct safety summary, and the registry defines both the event category and the observation timeframe. But those counts come from a single-group sequence rather than from a randomized comparison. That design distinction determines what the data can answer.

The three phases help organize the timing of observations: oral pretreatment, intravenous treatment, and oral follow-up. The same 21 participants are listed at risk in each phase. This structure gives context to when the reported events occurred, but it does not create independent treatment groups. The oral phases cannot serve as concurrent controls for the intravenous phase because they occur at different times in the same study sequence.

The record also demonstrates the importance of keeping participant counts distinct from event counts and unique-person totals. Each phase reports participants with events, but the overall number of unique participants affected across the full timeframe is not reported. Avoiding a sum across phases prevents an unsupported conclusion about how many people experienced at least one event during the whole study.

Finally, descriptive results and inferential results serve different purposes. The phase counts communicate observed events. Without reported uncertainty estimates or an appropriate comparative analysis, they do not quantify a treatment contrast or its precision. The listed planning assumptions do not change this: they describe hypothetical sample-size illustrations, not a randomized design or observed power for the completed study.

These distinctions are useful in clinical research more broadly. Event definitions, analysis populations, observation windows, missing-data handling, and comparator structure all affect how safety data can be interpreted. In this record, the event definition and primary population are stated, while several statistical details are not reported. Recognizing both what is documented and what is absent keeps the interpretation aligned with the evidence available.

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 principal limitation for interpreting the serious adverse event counts is the uncontrolled, single-group design. The study has no concurrent comparator and no randomized allocation. Its oral pretreatment, intravenous treatment, and oral follow-up periods occur in sequence, so differences in observed counts across phases cannot isolate the effect of administration route.

The phase-specific results do not establish the total number of unique participants with serious adverse events across the full timeframe. Participant overlap between phases is not specified, and an overall unique-participant result is not reported in the registry record. Event-level details, including timing, duration, recurrence, and outcome, are also not reported in the registry record.

Although 21 participants are listed at risk in each phase, the record does not state whether all participants completed every phase or describe incomplete follow-up. Missing-data handling and other analysis populations are not reported in the registry record. The primary endpoint population is defined, but that does not resolve how incomplete observations were treated.

No confidence intervals, hypothesis tests, or comparative estimates for the serious adverse event results are reported in the registry record. The statistical analysis plan, multiplicity strategy, and protocol-based sample-size justification are also not reported in the registry record. Consequently, the precision of the observed event counts and the approach to secondary outcomes cannot be evaluated from the reported information.

The registry lists seizure frequency and plasma concentration as secondary outcomes but does not report their numerical results in the information described. The serious adverse event figures therefore cannot answer questions about those outcomes. The study's stated purpose and population are clear, but the limited reported analyses and the absence of a comparator constrain conclusions to description rather than comparative or causal inference.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Intravenous Perampanel in Japanese Participants With Epilepsy — NCT03754582.
• Registry record last updated 2021-01-05; status last verified 2019-11.
• Results first posted 2021-01-05.
• 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, multicenter, uncontrolled, open-label, single-group study of intravenous perampanel in Japanese participants with epilepsy. Enrollment was 21. Participants received oral perampanel during a 28-day pretreatment phase, followed by intravenous perampanel over 30 minutes, then oral perampanel during follow-up. The study focused on participants with partial onset seizures, including secondarily generalized seizures, or primary generalized tonic-clonic seizures.

The primary endpoint was the number of participants with serious adverse events during a timeframe of up to 60 days. Phase-specific counts were 0 during pretreatment, 1 during intravenous treatment, and 2 during follow-up; 21 participants were listed at risk in each phase. No deaths were listed in the phases. The record does not report an overall unique-participant count for the full timeframe or a comparative analysis.

Seizure frequency and plasma concentration are listed as secondary outcomes, but their numerical results are not reported in the registry record. Statistical analysis details, missing-data methods, and a multiplicity strategy are also not reported in the registry record. The safety counts should be interpreted descriptively in light of the single-group, sequential design.