PART A: Efficacy and Safety of AEVI-001 in Children and Adolescents With ADHD and With mGluR Mutations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PART A: Efficacy and Safety of AEVI-001 in Children and Adolescents With ADHD and With mGluR Mutations (NCT03265119), a randomized phase 2 study. The primary outcome is Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score.

2. Clinical Question

The trial record concerns Part A of a two-part study. Its broader description refers to children and adolescents with ADHD with or without copy number variants in specific genes; the Part A summary narrows the enrolled group to participants determined to have specific gene mutations implicated in glutamatergic signaling and neuronal connectivity. The record does not give further detail about the genetic criteria or the distribution of mutations among participants.

The primary measure is a continuous symptom-rating total, while the posted secondary outcome is a global-improvement response. These outcomes address related but distinct questions: one records change on a symptom scale, and the other counts participants classified as responders on a global impression measure. Neither outcome alone describes every aspect of a participant’s experience.

3. Trial Design

This was a phase 2, randomized, double-blind, parallel-design study with placebo control. The official title describes a multicenter, two-part, six-week study. The registry record identifies the trial status as completed, an enrollment of 69, a start date of 2017-08-28, and a primary completion date of 2018-09-24. The brief summary identifies Part A as a dose-optimization study; arm-level dose information is not reported in the registry record.

The posted comparison is between AEVI-001 and placebo. For the primary outcome, the registry identifies the Full Analysis Set and reports 33 participants for AEVI-001 and 34 for placebo. The safety summaries use denominators of 34 and 35, respectively. The record does not explain the difference between these outcome-specific denominators and the safety denominators, or provide a participant-flow account that would clarify it. The total enrollment should therefore not be treated as the analysis denominator for every outcome.

The primary endpoint timeframe is baseline to Visit 8 (Week 6). The study title and brief summary describe a six-week treatment period. The registry record does not report additional visit timing, treatment adherence, the actual dose schedules, or details of how dose optimization was conducted.

The registry record does not report the randomization sequence method, allocation concealment, the identities of the masked groups, or the original statistical analysis plan. It also does not report the original sample-size justification or the assumptions used when the trial was designed. These details should not be inferred from the randomized, double-blind, parallel-design labels 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set

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 Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score, measured over Baseline to Visit 8 (Week 6).

The primary endpoint is change from baseline in the Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) total score, assessed at Visit 8 (Week 6). The scale includes 18 frequency items and 12 impairment items, but its total score is calculated from the 18 frequency-item scores. Each frequency item ranges from 0, meaning never or rarely, to 3, meaning very often. The total score ranges from 0 to 54, with higher scores indicating greater symptom severity.

Change is defined as the assessment value minus the baseline value. A negative change therefore indicates that the score at follow-up was lower than at baseline. The reported endpoint is a least-squares mean, with standard error as the accompanying measure of dispersion. Least-squares means are model-based group summaries in general; the specific model and any covariates used for this trial are not reported in the registry record.

A symptom-scale change is useful for comparing the direction and magnitude of score movement between randomized groups over a defined interval. It is not identical to a responder outcome: a group mean can describe average change without showing how many individual participants experienced a particular degree of improvement. The registry record does not report a threshold on the ADHD-RS-5 that would define a clinically important change, so the posted mean changes should be read as scale results rather than as counts of participants meeting a response criterion.

7. Results Posted in the Registry

• AEVI-001: mean -9.17 versus -11.34 on control; difference 2.17 (95% CI -3.87 to 8.21), standardized effect d = 0.17; z-test p = 0.481.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Clinical Global Impression - Global Improvement (CGI -I) Response

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • AEVI-001: 27.3% (9/33) versus 32.4% (11/34) on control; risk difference -5.1 percentage points (95% CI -26.9 to 16.8), risk ratio 0.84 (0.40–1.77); unadjusted two-proportion z-test p = 0.650.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AEVI-001 and the control. The interval gives the range of effects that remain compatible with the data.

The registry record lists one secondary outcome: Clinical Global Impression–Global Improvement response at Visit 8 (Week 6). It records 9 responders among 33 participants in the AEVI-001 group and 11 among 34 in the placebo group. The unadjusted comparison has a p-value of 0.65, and its risk-difference interval spans zero. These summaries indicate substantial uncertainty about the between-group response contrast; they do not establish equality or a reliable difference.

The secondary measure is related to the primary ADHD-RS-5 change outcome because both concern status over the same study period, but they are not interchangeable. The primary outcome summarizes average change on a symptom-severity scale. The secondary outcome counts participants classified as global-improvement responders. The two measures can show different patterns because they capture different aspects of outcome and use different statistical summaries. The secondary result therefore adds context, but it does not replace or resolve the uncertainty in the primary result.

Unadjusted secondary results carry less weight when multiple outcomes or comparisons may be examined because the chance of obtaining an apparently notable result can increase as the number of tests grows. Statistical methods can address multiplicity by controlling an error rate or by specifying a hierarchy among outcomes, but the registry record does not report whether any such procedure was planned or used. The posted secondary p-value should therefore be treated as an unadjusted summary rather than as a definitive standalone test.

The record lists one secondary endpoint and no reported analyses for it. It does not provide a detailed analysis plan, missing-data method, or explanation of how responder status was assigned. Those omissions make it difficult to assess the intended inferential role of the endpoint or the robustness of its result. The overall pattern is that neither the primary summary nor the secondary response comparison gives a precise separation between groups; the secondary outcome does not materially settle the primary endpoint’s uncertainty.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Clinical Global Impression - Global Improvement (CGI -I) Response

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant’s ADHD-RS-5 total score can take values across a numeric scale, and the registry reports group-level least-squares mean changes. The arm summaries are -9.17 for AEVI-001 and -11.34 for placebo. A mean is a measure of the central location of a set of values. It captures average score change, but it does not show the distribution of individual changes, whether outcomes were similar across participants, or how many participants had a particular response.

What does the mean difference represent?

The comparison is expressed as AEVI-001 minus placebo. The unadjusted recalculated difference is 2.17 units. Since change was calculated as follow-up score minus baseline score, negative values correspond to lower scores at follow-up. The positive contrast means that the AEVI-001 group’s reported average change was less negative than the placebo group’s reported average change. The contrast is a group comparison, not a statement about every participant, and it does not by itself show why the groups differed.

The word unadjusted matters. The comparison is a simple recalculation from the posted group summaries rather than a documented adjusted treatment estimate from a described statistical model. The registry record does not report the model specification, adjustment variables, or a sponsor analysis for the primary comparison. The least-squares mean label indicates a model-based type of summary in general, but it does not reveal which model was fitted in this trial. The group summaries and the recalculated contrast should not be mistaken for a fully documented analysis plan.

What does the standard error describe?

The reported dispersion for each group is a standard error: 2.235 for AEVI-001 and 2.122 for placebo. A standard error describes the estimated precision of a statistic such as a mean, reflecting how much that estimate would tend to vary across repeated samples under the assumptions of the method. It is not the same as the spread of individual participant scores. The standard error alone does not describe all features of the data, including skewness, outliers, or variation between participants.

In general, the standard error is used in constructing a confidence interval and assessing how compatible the estimate is with a range of possible underlying values. It depends on both variability and sample size, among other features of the analysis. The registry record does not give the participant-level distribution or the exact model used to obtain the reported least-squares means and standard errors, so those features cannot be assessed from these summaries.

How should the confidence interval and p-value be read?

The 95% confidence interval for the unadjusted mean difference runs from -3.87 to 8.21. In general, a confidence interval is a range generated by a statistical procedure that, under its assumptions, is designed to cover the target quantity at the stated rate over repeated use. For one trial, the interval communicates the precision and range of values reasonably compatible with the data and method; it is not a probability statement about the fixed true value.

The interval includes zero, the value corresponding to no difference under the contrast definition. Its lower endpoint is negative and its upper endpoint is positive, so it includes differences in either direction. The interval also spans a meaningful range of possible contrast values, which limits precision. The registry record does not supply a clinical interpretation threshold for the ADHD-RS-5 contrast, so statistical uncertainty cannot be translated into a judgment about clinical importance from the posted information alone.

The unadjusted p-value of 0.481 measures, under the statistical model and a no-difference null hypothesis, how unusual a result at least as incompatible with that null would be. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. A p-value should be read with the estimate and confidence interval, not used as a stand-alone verdict. The registry record does not state the test used for this comparison.

Why can over-dispersion matter?

Over-dispersion is a general concern when observed variability is greater than a statistical model assumes. If the model understates variability, standard errors can be too small and confidence intervals too narrow; if it accounts for variability poorly in another way, inference may also be affected. This issue is especially relevant to count or binary outcomes when a simple model assumes more uniformity than the data support. The record does not provide the participant-level data or model diagnostics needed to assess over-dispersion for these outcomes. The primary endpoint is continuous, and no claim about over-dispersion in this trial can be made from the posted summaries.

The secondary outcome is binary at the participant level: a participant is counted as a responder or not. It reports 9 responders among 33 in the AEVI-001 group and 11 among 34 in the placebo group. A risk difference compares the response proportions in the two groups; the posted unadjusted comparison gives a risk difference of -0.051, with an interval that spans zero. The record also gives an unadjusted p-value of 0.65. The reported risk-difference estimate is recalculated from the posted counts, and it should be interpreted with the same caution about uncertainty and the absence of a reported analysis plan.

Finally, statistical significance and clinical importance are separate questions. A test can address compatibility with a specified null value under assumptions; clinical importance requires an interpretive threshold and context. No such threshold is reported for the primary endpoint, and the registry record does not report the original analysis plan or missing-data procedures. These gaps constrain how far the numerical summaries can be interpreted.

11. Confidence Intervals and Precision

The primary unadjusted recalculated mean difference is 2.17 ADHD-RS-5 units, with a 95% confidence interval from -3.87 to 8.21. The estimate is a single point on a range of plausible values under the method used. The interval extends below and above zero, so it is compatible with differences in either direction, including no difference. It is also broad enough that the size and direction of a group contrast remain uncertain.

Precision is not the same as whether an estimate is statistically significant or clinically important. The point estimate gives the best single summary under the calculation, while the interval shows the uncertainty around it. Because the interval includes zero, the estimate does not distinguish a difference from no difference at the usual inferential level represented by a 95% interval. But that does not establish equality: values away from zero are also included. The registry record does not report a threshold for a clinically important ADHD-RS-5 difference, so the interval cannot be classified against such a threshold.

The arm-level standard errors are 2.235 for AEVI-001 and 2.122 for placebo. These describe precision of the reported means, not the variability among individual participants. The record does not provide individual-level values, distributions, or enough model detail to independently assess the assumptions behind the interval.

For the secondary responder outcome, the registry reports an interval for the risk difference that spans zero. That means the posted data do not sharply separate a group difference from no difference on that measure either. The secondary estimate has its own uncertainty and should not be used to narrow the primary endpoint’s uncertainty. Taken together, the endpoint summaries are not precise evidence for a clear between-group separation, but they also do not demonstrate that the groups are equivalent.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total sample sizes or total events. They are illustrations calculated from observed effects, not the original trial’s design assumptions. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The trial’s original sample-size justification and design assumptions are not reported in the registry record.

For the primary outcome, planning for 100% of the observed effect gives 530 participants per arm for 80% power and 710 participants per arm for 90% power. Planning for 75% of the observed effect gives 942 participants per arm for 80% power and 1,261 participants per arm for 90% power. Planning for 50% of the observed effect gives 2,119 participants per arm for 80% power and 2,837 participants per arm for 90% power.

The secondary-outcome planning illustration also uses participants per arm. Its corresponding figures are 1,272 and 1,702 for 100% of the observed effect, 2,289 and 3,064 for 75%, and 5,211 and 6,975 for 50%, for 80% and 90% power, respectively.

In general, 80% power means that a study designed under the stated assumptions would have an 80% chance of detecting the specified effect using the stated test procedure if that effect were the true one. The 90% column uses a higher target chance under those same assumptions. Smaller effects need more participants to detect reliably, which is why the planning figures rise as the target fraction of the observed effect falls. These are planning illustrations, not observed power for this completed trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 2.170; pooled standard deviation σ = 12.605.
2. n = 2 × (1.96 + 0.842)² × 12.605² / 2.170² = 529.6, rounded up to 530 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 2.17                      # observed difference in means
sigma <- 12.6047570067812                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3265119)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 530 (80% power), 710 (90% power)
 75% of observed effect: n per arm = 942 (80% power), 1,261 (90% power)
 50% of observed effect: n per arm = 2,119 (80% power), 2,837 (90% power)
power.t.test: 530.6 
Simulated power at n = 530 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when more than one outcome, comparison, time point, or analysis is tested. In general, examining multiple tests without an adjustment can increase the chance that at least one result appears noteworthy by chance. The registry record lists a primary outcome and one secondary outcome. It does not report whether a multiplicity adjustment, hierarchical testing strategy, or other procedure was specified. The primary comparison is presented with an unadjusted p-value, and the secondary comparison is also unadjusted. No adjustment should be assumed.

The registry record identifies the Full Analysis Set for the primary endpoint, but does not define the set in detail. It does not report the inclusion rules, how participants were handled if they discontinued, or the exact populations used for the secondary and safety summaries. The primary endpoint group counts are 33 and 34, while the safety denominators are 34 and 35. The record does not explain those differences. Enrollment was 69, but the record does not provide a complete participant flow that would show how enrollment relates to each analysis population.

Missing outcome data can affect group estimates if data are unavailable for some participants. In general, the impact depends on how much data are missing, why they are missing, and how the analysis handles them. The registry record does not report the amount or pattern of missing primary or secondary outcome data, a missing-data method, or sensitivity analyses exploring alternative assumptions. It is therefore not possible to determine from the posted information how missingness may have influenced the estimates.

The original statistical plan, protocol-level analysis details, and any interim-analysis plans are not reported in the registry record. The sample-size illustrations available with the posted results use observed effects and stated planning assumptions; they are not evidence of the original design rationale. These gaps do not invalidate the reported summaries, but they limit assessment of whether the analyses followed a prespecified plan and how robust the inferences are to alternative choices.

15. 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: irritability (2.9%).

The registry-recorded serious adverse event summaries use safety denominators of 34 participants for AEVI-001 and 35 for placebo. One participant in the AEVI-001 group and none in the placebo group are listed as affected by a serious adverse event. No deaths are listed in either group. The record lists irritability at 2.9% among the top serious adverse event terms, but does not identify the group associated with that term in the posted term summary.

These are counts from the safety summaries, not estimates of comparative risk with a stated uncertainty interval. With these denominators, a small number of events cannot characterize uncommon risks precisely. The record does not provide event narratives, timing, duration, severity grading beyond the serious-event classification, or a detailed causal assessment. The serious-event counts alone therefore do not establish whether an event was caused by study treatment.

The registry also reports other adverse events affecting 12 participants in the AEVI-001 safety group and 11 in the placebo safety group. Those figures are distinct from the serious adverse event counts. Safety summaries describe the events recorded in this trial; they should not be read as a complete estimate of risk beyond the study population and observation period.

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

The posted primary result describes average ADHD-RS-5 score changes from baseline to Week 6 in the Full Analysis Set. Both groups had negative mean changes, and the estimated unadjusted difference was 2.17 units in the AEVI-001-minus-placebo direction. The confidence interval, from -3.87 to 8.21, includes zero and extends in both directions. The result is therefore uncertain about the direction and magnitude of the between-group contrast.

This does not establish that the groups are the same. An interval that includes zero can also include nonzero differences, and the posted interval includes a range of them. Nor does the result establish a difference: the estimate is imprecise, and the unadjusted p-value is 0.481. A p-value is not a measure of the probability that a treatment works, nor is it a direct measure of clinical importance. The registry record does not state a threshold for an important ADHD-RS-5 change.

The endpoint measures average score change, not the experience or response of every participant. The secondary global-improvement outcome counts responders using a separate classification; its comparison is also uncertain. The two outcomes should be considered together as distinct summaries, without allowing one to stand in for the other.

The trial record describes a randomized, double-blind, placebo-controlled design, which is relevant to interpreting a comparative study. However, details about randomization, masking, missing-data handling, the original analysis plan, and multiplicity are not reported. The primary and safety denominators also differ, without a participant-flow explanation. These limitations mean that the posted outcome summaries cannot answer every question about the conduct or robustness of the analysis.

The trial’s posted results describe what was recorded for this study and these outcomes over the stated period. They do not establish whether AEVI-001 is beneficial or ineffective, and they do not determine how findings would apply beyond the participants and circumstances represented in the record. No medical decision should be inferred from these statistical summaries alone.

17. Why This Trial Matters Statistically

This trial illustrates why a group difference should be read alongside its uncertainty. The primary point estimate is 2.17 ADHD-RS-5 units, but its 95% confidence interval runs from -3.87 to 8.21. The point estimate by itself gives a simple direction under the AEVI-001-minus-placebo convention; the interval shows that the data are compatible with values in either direction. The practical statistical message is not captured by a single estimate or p-value alone.

It also highlights the distinction between a continuous endpoint and a responder outcome. The ADHD-RS-5 result summarizes average score change, while the CGI-I result counts responders. They can complement one another, but they answer different questions and have different statistical properties. The registry lists one secondary outcome, and the available secondary comparison is unadjusted. Its inferential role depends on a multiplicity plan that is not reported.

The record offers enough information to describe the trial’s basic design, endpoint, arm summaries, and selected safety counts. At the same time, it leaves important analysis details unresolved: original sample-size assumptions, model specification, missing-data handling, participant flow, and multiplicity procedures are not reported. Distinguishing known results from unreported methods is central to a careful reading of registry data.

Finally, the planning illustrations demonstrate how sample-size requirements change with the effect targeted and desired power. They are based on observed effects and stated assumptions, rather than the trial’s original design rationale. Keeping that distinction clear prevents planning calculations from being mistaken for evidence that the completed study had a particular probability of success.

18. 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 primary comparison is an unadjusted recalculation from posted summary statistics. The registry record does not report a sponsor-reported inferential analysis, the statistical model specification, or covariates that may have been used to obtain the least-squares means. The reported confidence interval and p-value should therefore be understood in the context of the available summary, not as a substitute for a fully described prespecified analysis.

There is limited information about participant disposition. Enrollment is 69, primary outcome counts are 33 and 34, and safety denominators are 34 and 35. The registry record does not explain the differences between these populations or report the reasons for missing outcome data, discontinuations, or exclusions. No missing-data approach or sensitivity analysis is reported.

Part A’s description refers to participants with specific gene mutations, but the registry record does not report which mutations were represented, their frequencies, or how the eligibility criteria were operationalized. Arm descriptions do not specify dose levels or dose optimization details. The record also does not provide the original sample-size rationale, randomization procedure, allocation concealment details, masking roles, or protocol-level statistical plan.

Only one secondary outcome is listed, and no reported analyses are listed for it. The posted secondary comparison is unadjusted; no multiplicity procedure is reported. The result therefore has limited inferential context. The registry record also does not provide a threshold for a clinically important primary-score difference, which limits interpretation of the numerical contrast in clinical terms.

Safety summaries are counts with no reported comparative uncertainty analysis or detailed event-level information. The record lists one serious adverse event affected participant in the AEVI-001 group and none in the placebo group, but does not provide enough detail to assess event timing, attribution, or the broader safety profile. These limitations are specific to the information recorded and should be kept distinct from claims about what was or was not collected during the trial.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: PART A: Efficacy and Safety of AEVI-001 in Children and Adolescents With ADHD and With mGluR Mutations — NCT03265119.
• Registry record last updated 2021-07-07; status last verified 2021-07.
• Results first posted 2019-07-16.
• 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.

22. Record Summary

NCT03265119 is a completed phase 2, randomized, double-blind, parallel-group, placebo-controlled study of AEVI-001 in children and adolescents ages 6–17 years with ADHD. The record describes Part A as a six-week dose-optimization study in participants with specific gene mutations implicated in glutamatergic signaling and neuronal connectivity. Enrollment was 69.

The primary outcome was change from baseline in ADHD-RS-5 total score at Visit 8 (Week 6), in the Full Analysis Set. The reported mean changes were -9.17 for AEVI-001 and -11.34 for placebo; the unadjusted recalculated mean difference was 2.17, with a 95% confidence interval from -3.87 to 8.21 and an unadjusted p-value of 0.481. One secondary outcome, CGI-I response, was posted. The safety summaries list one serious adverse event affected participant in the AEVI-001 group and none in the placebo group, with no deaths listed.

The record does not report the original sample-size justification, detailed analysis plan, missing-data method, multiplicity procedure, or a complete participant-flow explanation.