This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Amantadine for the Treatment of Traumatic Brain Injury Irritability and Aggression: A Multi-site Study (NCT00779324), a randomized na study. The primary outcome is Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Observer Day 28.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00779324 |
| Phase | NA |
| Condition | Brain Injury, Aggression |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 168 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Wake Forest University Health Sciences |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with chronic traumatic brain injury and irritability or aggression. The registry record does not report detailed eligibility criteria or describe the enrolled participants’ clinical characteristics, so the population cannot be characterized more narrowly from the posted information.
Intervention
The intervention was amantadine hydrochloride. The amantadine arm is described as receiving 100 mg every morning and Noon. The registry record does not give further treatment-administration details.
Comparator
The comparator was placebo tablets. The study is described as placebo-controlled, randomized, parallel-group, and quadruple-masked.
Primary question
At Day 28, what proportion of participants in each arm met the registry’s primary Neuropsychiatric Inventory irritability criterion, and how did the arm percentages compare? The stated criterion is a greater-than-two-point increase in the observer-rated irritability domain. The registry also uses wording that calls the outcome an improvement, so the direction is not consistently labelled.
The primary outcome focuses on an observer’s rating of irritability rather than a general measure of traumatic brain injury recovery. The reported arm percentages were 66.3 for amantadine and 66.7 for placebo. The registry-reported comparison is a difference in percents, with a confidence interval and p value. Those statistics describe uncertainty in the arm contrast; they do not by themselves establish the clinical importance of any difference. The registry record does not report a threshold for a clinically important between-arm difference or detailed eligibility criteria that would show how broadly the findings might apply.
3. Trial Design
The registry describes a randomized, parallel-group study comparing amantadine hydrochloride with placebo. Masking is listed as quadruple, and the study is described as placebo-controlled. The amantadine arm is specified as 100 mg every morning and Noon; the placebo arm received placebo tablets. The record does not explain which people were included in the quadruple masking or provide further details about how randomization and treatment allocation were carried out.
The study title and brief description identify the topic as irritability and aggression associated with traumatic brain injury, and the official title describes the study as a replication study in chronic traumatic brain injury. The registry lists an enrollment of 168. For the primary endpoint, it lists 80.0 for the amantadine arm and 81.0 for the placebo arm. The record does not explain the relationship between the enrollment figure and the arm counts reported with this endpoint, or state which analysis population those endpoint counts represent.
The recorded start is 2009-08, primary completion is 2013-04, and status is completed. The sponsor is Wake Forest University Health Sciences. The phase is listed as NA. The registry includes a Day 28 primary outcome and secondary outcomes at Day 28 and Day 60, including observer- and participant-rated irritability measures and Clinical Global Impressions. These outcome listings identify the measures and time points; they do not, by themselves, establish which results were prespecified for every analysis or how missing observations were handled. Those details are not reported in the registry record.
The treatment comparison is randomized, but the record does not report the randomization procedure, allocation concealment details, treatment adherence, or reasons for discontinuation. It also does not give a detailed protocol description or explain whether participants could receive other care during the trial. These omissions limit what can be inferred about trial conduct from the registry entry alone.
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
| Stage | Amantadine | Placebo |
|---|---|---|
| STARTED | 82 | 86 |
| Completed 28-day Mid-point | 80 | 81 |
| COMPLETED | 75 | 82 |
| NOT COMPLETED | 7 | 4 |
Reasons for not completing this period:
| Reason | Amantadine | Placebo |
|---|---|---|
| Lost to Follow-up | 2 | 1 |
| Withdrawal by Subject | 4 | 2 |
| Missed visit | 1 | 1 |
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.
| Characteristic | Unit | Amantadine | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 82 | 86 | 168 | |
| Age, Continuous | years | 40.18 (SD 12.67) | 38.23 (SD 12.36) | 39.21 (SD 12.52) |
| Sex: Female, Male: Female | Participants | 18 | 20 | 38 |
| Sex: Female, Male: Male | Participants | 64 | 66 | 130 |
6. Primary Endpoint
The registry lists the primary outcome as Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Observer Day 28, measured over Day 28.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants NPI improve>2 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the proportion of participants described as having a greater-than-two-point increase on the observer-rated Neuropsychiatric Inventory irritability domain at Day 28. The Neuropsychiatric Inventory is described as a 40-item scale covering 12 behavioral domains; this study used only the irritability domain. The domain includes items concerning temper, mood changes, anger, impatience, crankiness, and argumentativeness. The rater selects frequency and severity for the most problematic behavior over the preceding month, and the score is the product of those ratings. The registry gives the domain’s total range as 1, least irritability, to 12, worst irritability.
A proportion meeting a stated threshold can make an outcome easier to interpret as a countable event: participants are classified according to whether they meet the criterion, and the arm percentages can be compared. That form also discards information about how far scores change for participants who do not cross the threshold. The registry does not report the rationale for choosing the greater-than-two-point threshold.
There is a wording issue that matters for interpretation. The primary outcome title and description refer to an increase, while the unit wording calls it an improvement. Because the registry describes higher scores as worse irritability, those labels do not point in the same direction. The reported percentages can be described, but the record does not resolve that inconsistency. The endpoint is observer-rated; participant-rated irritability appears among the secondary outcomes, not as the primary measure.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry lists the primary endpoint percentages as 66.3 for amantadine and 66.7 for placebo. Its reported comparison is a difference in percents of -0.4, with a 95% confidence interval from -14.7 to 13.9 and p = 0.955. The comparison is listed as Chi-squared. The figures describe the observer-rated Day 28 irritability endpoint as recorded in the registry; they do not establish that the treatment caused any observed difference.
The confidence interval expresses uncertainty around the estimated difference. In general, a confidence interval shows a range of values compatible with the data and the method used to construct it. This interval extends on both sides of zero, so it includes no difference as well as differences in either direction. Its breadth means the estimate is not precise enough to pin down a narrow range of possible contrasts. The registry does not report a clinically important difference threshold, so the interval cannot be classified against such a threshold from the posted information.
The p value is reported as 0.955. In general, a p value describes how unusual data at least as inconsistent with a null hypothesis would be under the assumptions of a specified statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The registry result does not provide evidence of a clear separation between the arm percentages under the reported test, but that does not prove that the arms are equivalent or that no potentially important difference exists. Establishing equivalence would require an appropriate design and a prespecified equivalence margin, neither of which is reported in the registry record.
Direction requires particular care. The title and outcome description define the primary event as a greater-than-two-point increase, while the unit description refers to improvement. The registry says that the score ranges from 1 for least irritability to 12 for worst irritability. Thus, an increase in score and an improvement label do not align on their face. The arm percentages should be read as the registry reports them, without silently changing the event definition or treating the endpoint as a reduction in irritability. The record does not resolve the inconsistent wording.
The registry lists outcome counts of 80.0 for amantadine and 81.0 for placebo beside the primary endpoint. It does not say whether those counts represent all randomized participants, participants with an observed Day 28 assessment, or another analysis population. Nor does it report how missing ratings were treated. Accordingly, the percentages and test can be reported as posted, but the analysis population and the influence of missing data cannot be assessed from this entry alone.
Overall, the posted result is a near-zero estimated difference in the reported percentages, accompanied by a confidence interval that allows a range of contrasts in either direction. This is a description of the registry result, not a conclusion about treatment effectiveness. The endpoint-label inconsistency, unreported analysis-population details, and lack of a stated clinical-importance threshold all constrain what can be concluded from the number alone.
9. Statistical Methods Explained
The primary comparison concerns a binary outcome: whether a participant met the registry’s stated threshold on the observer-rated irritability domain at Day 28. For a binary endpoint, each arm can be summarized by the proportion meeting the criterion. The registry lists 66.3 for amantadine and 66.7 for placebo, and reports a difference in percents of -0.4. The record does not explain the coding convention used to order the subtraction, so the sign should be read as part of the reported contrast rather than reinterpreted as a direction of benefit.
What does the Chi-squared test assess?
The reported method is Chi-squared. In general, a Chi-squared test can assess whether the distribution of a categorical outcome differs between groups. For this endpoint, the relevant categories are whether or not the specified threshold was met. The test evaluates the evidence for an association between treatment group and the categorical outcome under its statistical assumptions; it does not directly estimate clinical importance. The registry reports p = 0.955 for this comparison. Details about the exact implementation, assumptions checks, or any alternative analyses are not reported in the registry record.
How should the confidence interval be read?
The registry reports a 95% confidence interval from -14.7 to 13.9 for the difference in percents. In general, a confidence interval conveys uncertainty about an estimated quantity under the model and procedure used. It is not a range containing 95% of individual participant outcomes, nor does it mean that each value in the range is equally plausible. Here, the interval spans zero and includes contrasts in either direction. Its width indicates that the point estimate alone should not be treated as a precise description of the possible arm difference. The record does not identify a threshold for a clinically important difference, so the interval cannot answer whether any particular value would matter clinically.
What is the role of the outcome threshold?
The primary endpoint reduces the observer-rated domain score to whether a participant had a greater-than-two-point increase. In general, converting a scale to a threshold outcome can make an event proportion straightforward to communicate, but it omits information about score changes that do not cross the threshold. It can also make results sensitive to the selected cutoff. The registry does not report why this threshold was selected or whether it was prespecified in a protocol. The record also labels the event inconsistently: its title and description say increase, while its unit wording says improvement. The score range is given as 1 for least irritability and 12 for worst irritability. Those details make the discrepancy relevant, but the registry does not provide a clarification.
What can be said about the reported test and estimate?
The reported estimate is -0.4, and the confidence interval extends from -14.7 to 13.9. The p value is 0.955. In general, these statistics answer related but distinct questions: the estimate describes the observed contrast, the interval describes uncertainty around it, and the p value summarizes compatibility with a null hypothesis under a test. None is a direct measure of the probability that treatment is effective, and a large p value is not proof of equivalence. Interpretation also depends on the outcome definition and the population included in the analysis.
The record lists 80.0 for the amantadine arm and 81.0 for the placebo arm with this endpoint, while the enrollment is 168. The relationship between those figures is not explained, and the analysis population is not identified. The record does not report whether the analysis followed intention-to-treat principles, how missing endpoint measurements were handled, or whether any participants were excluded from the primary analysis. These are important details for understanding how a randomized comparison was preserved and how the reported estimate might be affected by unavailable assessments.
How should planning illustrations be distinguished from trial results?
Planning illustrations based on the observed effect are hypothetical design calculations, not observed trial outcomes and not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning quantity is participants per arm for 80% or 90% power, as applicable to the displayed illustration. Those assumptions describe the illustration rather than the trial’s own design rationale. The registry record does not report the original sample-size justification or the assumptions used when the trial was planned.
In general, such calculations depend on the assumed effect, variability or event frequency, allocation, significance level, and statistical method. If the assumed effect is based on the observed estimate, the resulting illustration is conditional on that estimate and should not be read as evidence that the completed trial had a particular probability of detecting an effect. The registry does not report interim analyses, a detailed statistical analysis plan, or other design-stage calculations.
Why do multiplicity and missingness matter?
The registry lists a primary outcome and multiple secondary measures, including observer- and participant-rated irritability at Day 28 and Day 60 and Clinical Global Impressions at Day 28. It reports 10 outcome measures, 8 analyses, and 9 posted secondary outcomes. When several outcomes or analyses are considered, the chance of obtaining at least one apparently notable result can increase if each is tested separately. In general, multiplicity procedures can address that issue, but the registry record does not report whether any adjustment was used or which outcomes were included in a prespecified testing strategy.
Missing outcomes can also affect a proportion comparison if the availability of assessments differs between arms or is related to the outcome. In general, the handling of missing data is part of the analysis definition, not a detail that can be inferred from arm percentages. The registry does not report missing-data methods, analysis-population definitions, or sensitivity analyses for this endpoint. The posted estimate and test therefore need to be interpreted alongside those unreported details, rather than as a complete account of the analysis.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Chi-squared | Difference in percents -0.4 | -14.7 to 13.9 | 0.955 |
The registry-reported primary analysis is a Chi-squared comparison of the arm percentages. It gives a difference in percents of -0.4, a 95% confidence interval from -14.7 to 13.9, and p = 0.955. The arm percentages are 66.3 for amantadine and 66.7 for placebo. These are the posted figures for the primary endpoint.
No separate recalculated estimate is reported in the registry record, so there is no additional numerical result to compare with the listed analysis. The arm counts and percentages alone do not supply enough information to reconstruct every aspect of the reported test, including its exact implementation and analysis population. The posted result should therefore be read as the registry’s reported comparison, without presenting an independently calculated alternative.
The comparison’s direction also depends on the endpoint coding. The registry describes the event as a greater-than-two-point increase in one place and as improvement in another. Since the stated scale range identifies higher scores with worse irritability, that inconsistency is not resolved by the reported estimate or p value. The registry record does not provide further clarification of the event label.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and a collection of secondary outcomes. These include observer-rated and participant-rated irritability measures, proportions meeting a greater-than-two-point criterion, and Clinical Global Impressions. The record reports 10 outcome measures, 8 analyses, and 9 posted secondary outcomes. These counts describe the registry listings; they do not establish how many hypotheses were included in a formal testing strategy or whether the listed analyses were all prespecified.
When researchers examine multiple endpoints, time points, or analyses, separate tests can produce a notable result by chance even when each test uses a conventional threshold. In general, multiplicity methods can control or otherwise address that issue, but the registry record does not report whether any adjustment was made. It also does not state a hierarchy of outcomes, a gatekeeping plan, or which comparisons were considered confirmatory. The primary comparison can be described using its reported p value, but the broader set of outcomes cannot be interpreted as a single unadjusted collection of independent evidence.
Missing-data handling is also not reported. The registry lists 80.0 and 81.0 with the primary endpoint, but does not state whether these figures are randomized participants, participants with observed outcome data, or another analysis population. It does not describe the number of missing Day 28 ratings, reasons for missingness, imputation, or sensitivity analyses. Without those details, the potential effect of missing assessments on the percentages and comparison cannot be evaluated.
The registry record also does not specify whether the primary analysis followed intention-to-treat principles, whether any participants were excluded, or how participants were assigned to analysis populations. Randomization is reported as a design feature, but the method used to preserve that comparison in the endpoint analysis is not described. A protocol or full statistical analysis plan is not reported in the registry record, nor are interim analyses or a sample-size justification. These gaps do not change the posted statistics, but they limit assessment of prespecification, analysis choices, and the robustness of the result.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Amantadine | 3 | 82 | 3.7% |
| Placebo | 2 | 86 | 2.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Amantadine | 36 of 82 |
| Placebo | 33 of 86 |
Most frequent serious adverse event terms
| Event term | Organ system | Amantadine | Placebo |
|---|---|---|---|
| Myocardial infarction | Cardiac disorders | 0 of 82 | 1 of 86 |
| Other infection | Infections and infestations | 0 of 82 | 1 of 86 |
| Urinary tract infection | Infections and infestations | 1 of 82 | 0 of 86 |
| Paranoia | Psychiatric disorders | 1 of 82 | 0 of 86 |
| Other general medical | General disorders | 1 of 82 | 0 of 86 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Amantadine | Placebo |
|---|---|---|---|
| Other general medical | General disorders | 10 of 82 | 13 of 86 |
| Insomnia/ sleep disturbance | Nervous system disorders | 7 of 82 | 10 of 86 |
| Other | General disorders | 3 of 82 | 6 of 86 |
| headache | Nervous system disorders | 5 of 82 | 2 of 86 |
| Connstipation | Gastrointestinal disorders | 6 of 82 | 1 of 86 |
| Diarrhea | Gastrointestinal disorders | 5 of 82 | 1 of 86 |
Serious events with the highest arm-level rate: urinary tract infection (1.2%), paranoia (1.2%), other general medical (1.2%), myocardial infarction (1.2%), other infection (1.2%).
The registry lists serious adverse event figures separately from the primary efficacy endpoint. For amantadine, it reports 3 participants affected among 82 at risk; for placebo, it reports 2 affected among 86 at risk. It also reports other adverse events affecting 36 among 82 at risk in the amantadine group and 33 among 86 at risk in the placebo group. These are the registry’s posted counts, not a calculated comparison of risk between arms.
The listed serious-event terms each have a reported frequency of 1.2%: urinary tract infection, paranoia, other general medical, myocardial infarction, and other infection. The record does not establish from these figures alone whether the terms are mutually exclusive or whether one participant could contribute to more than one term. It also does not provide a comparative statistical analysis of serious adverse events. Death counts are not reported in the registry record.
Safety figures should be read with their denominators and definitions in mind. The serious-event at-risk counts differ from the counts listed alongside the primary endpoint, and the registry does not explain the relationship between these populations. The entry does not provide further information on event timing, duration, severity beyond the serious classification, or causal attribution. These counts describe what the registry reports; they should not be treated as proof that one arm was safer or less safe.
13. What the Result Does, and Does Not, Mean
The primary result describes the percentage of participants in each arm who met the registry’s observer-rated Day 28 irritability criterion. The reported percentages are 66.3 for amantadine and 66.7 for placebo. The registry’s estimated difference is -0.4, with a 95% confidence interval from -14.7 to 13.9 and p = 0.955. Together, these statistics show that the posted estimate is close to zero but imprecise, with an interval that includes contrasts in either direction.
That result does not establish equivalence, prove that there is no difference, or show that a clinically important difference is absent. The registry does not report an equivalence margin or a threshold for clinical importance. A confidence interval is informative precisely because it displays uncertainty as well as the point estimate; the interval is substantially broader than the near-zero estimate alone might suggest. The p value does not provide the probability that either treatment is effective or ineffective.
The endpoint wording further limits interpretation. The primary title and description refer to a greater-than-two-point increase, while the unit description calls the criterion an improvement. Since the registry states that higher scores correspond to worse irritability, the difference in labels matters for understanding what the percentages represent. No correction or clarification is reported in the registry record, so the result should not be relabelled as an improvement or worsening outcome without qualification.
The endpoint is observer-rated and does not capture every aspect of irritability, aggression, or recovery after traumatic brain injury. Participant-rated measures and other outcomes are listed as secondary outcomes, but their results are not included among the registry entries available for this interpretation. The posted primary result therefore should not be generalized to unreported outcomes or later time points.
Finally, the record does not identify the primary analysis population or explain missing-data handling. It also does not report a multiplicity strategy for the listed outcomes. Those omissions make it difficult to assess whether the reported comparison reflects all randomized participants, how unavailable ratings may have affected it, and how the primary result should be interpreted alongside other analyses. The appropriate reading is descriptive and bounded by the registry’s definitions and reported statistics.
14. Why This Trial Matters Statistically
This trial is statistically useful to examine because its primary outcome converts a behavioral rating scale into a threshold event and compares the resulting proportions between randomized arms. That setup illustrates how a clinical question can be expressed as a difference in percentages, while also showing that a threshold-based endpoint leaves out information about score changes that do not cross the cutoff.
The reported contrast is close to zero, but the confidence interval is wide and includes values in either direction. This makes the distinction between a point estimate and its precision especially important: a small estimated difference is not the same as a precise estimate of no difference. The reported p value is another piece of the inferential picture, not a substitute for the effect estimate, interval, outcome definition, or clinical context.
The record also offers a practical example of why endpoint wording must be checked carefully. It labels the primary event as a greater-than-two-point increase, but elsewhere calls it an improvement, even though its score description says higher scores mean worse irritability. Statistical interpretation cannot repair that ambiguity by assuming which wording was intended. Clear, consistent definitions are necessary for readers to know which event a percentage represents.
Several further interpretation issues are visible in the registry entry: multiple secondary outcomes are listed, but multiplicity procedures are not reported; the analysis population and missing-data methods are not specified; and the counts associated with the primary outcome differ from the enrollment figure without an explanation of their relationship. These are not numerical corrections to the reported comparison. They are questions about the context required to assess its reliability and scope.
The study therefore provides a compact case for reading clinical trial statistics together: define the endpoint, inspect the scale direction, distinguish estimate from uncertainty, and identify analysis details that the record does not state. The posted result can be accurately described, while conclusions beyond that description remain limited by the endpoint wording and unreported methods.
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 registry record does not describe detailed inclusion or exclusion criteria, participant characteristics, injury severity, or the timing and circumstances of the traumatic brain injury. Although the study concerns chronic traumatic brain injury, irritability, and aggression, the available description is insufficient to judge how closely a particular clinical population matches the enrolled population. The record also does not provide detailed information about concomitant care or treatment adherence.
The primary endpoint has an internal wording inconsistency. The title and description refer to a greater-than-two-point increase, while the unit wording describes an improvement. The record gives the scale direction as 1 for least irritability and 12 for worst irritability, but does not clarify the conflicting labels. This creates uncertainty about how to characterize the event represented by the percentages.
The analysis population and missing-data handling are not reported. Although the registry lists 80.0 and 81.0 alongside the primary endpoint and gives enrollment as 168, it does not explain how those figures relate or which participants contributed to the analysis. The record does not describe exclusions, missing Day 28 assessments, or sensitivity analyses. It also does not report whether the primary analysis followed intention-to-treat principles.
Further limitations are the absence of a reported sample-size justification, detailed statistical analysis plan, multiplicity procedure, or interim-analysis information. The record lists multiple secondary outcomes, but does not specify how their results were to be interpreted relative to the primary endpoint. A clinical-importance threshold for the primary difference is also not reported. These omissions restrict assessment of precision, prespecification, and the broader meaning of the result; they do not alter the figures reported for the primary comparison.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Amantadine for the Treatment of Traumatic Brain Injury Irritability and Aggression: A Multi-site Study — NCT00779324.
- Registry record last updated 2022-07-12; status last verified 2021-08.
- Results first posted 2021-09-10.
- 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.
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19. Record Summary
The registry describes a completed, randomized, quadruple-masked, parallel-group, placebo-controlled study of amantadine for irritability and aggression associated with chronic traumatic brain injury. Amantadine is described as 100 mg every morning and Noon, and the comparator is placebo tablets. The enrollment is listed as 168; the primary endpoint entries list 80.0 for amantadine and 81.0 for placebo.
The primary endpoint is the observer-rated Neuropsychiatric Inventory irritability criterion at Day 28. The registry reports percentages of 66.3 and 66.7, a difference in percents of -0.4, a 95% confidence interval from -14.7 to 13.9, and p = 0.955 using Chi-squared. The endpoint wording alternates between an increase and an improvement, and the record does not resolve that discrepancy.
Secondary outcomes include observer- and participant-rated irritability measures and Clinical Global Impressions. The registry does not report the analysis population, missing-data methods, multiplicity adjustment, or sample-size justification. Serious adverse event figures are listed as 3 affected among 82 at risk for amantadine and 2 among 86 at risk for placebo; deaths are not reported in the registry record.