XEN1101 for Major Depressive Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for XEN1101 for Major Depressive Disorder (NCT04827901), a randomized phase 2 study. The primary outcome is Change in Activation Within the Reward Circuit by fMRI.

2. Clinical Question

The trial’s stated aim was to examine the neuronal KCNQ2/3 potassium channel subtype as a potential treatment target for mood disorders through administration of the KCNQ-selective channel opener XEN1101. The posted primary outcome is a measure of reward-circuit activation, rather than a depression symptom score. The registry also lists symptom and pleasure measures as secondary outcomes.

The primary comparison concerns the difference between the average week-8 change in the two randomized groups. It does not, by itself, establish whether an individual participant experienced a particular change, nor does it answer every question about symptoms, functioning, or safety. Those require separate outcomes and analyses.

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group phase 2 trial, with XEN1101 and placebo as the two drug interventions. Enrollment was 60. The posted primary outcome summaries include 29 participants in the XEN1101 group and 31 in the placebo group. The record is marked completed. Its stated start date is 2021-10-19, and its primary completion date is 2024-10-03.

Participants assigned to XEN1101 were to take two 10 mg capsules each day for eight weeks, a total daily dose of 20 mg. Participants assigned to placebo were to take matching placebo daily for eight weeks. The primary measurement was defined as change from baseline at week 0 to the end of treatment at week 8. The registry lists the group summaries as least-squares means with standard errors.

Random allocation is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. Masking is intended to reduce the influence of expectations or knowledge of assignment on participants, study staff, outcome assessment, and other trial processes. The registry labels the masking quadruple but does not report which roles were masked or the procedures used to maintain masking.

Other details of the design are not reported in the registry record. These include the eligibility criteria, the method used to generate and conceal the random allocation, the planned sample-size justification, the planned analysis populations, and the handling of missing outcome data. The registry record also does not describe whether there were interim analyses or specify the trial’s full statistical analysis plan. Those omissions limit how much can be concluded about the conduct and prespecification of the analyses from the record 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:

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 in Activation Within the Reward Circuit by fMRI, measured over Baseline (week 0), End of treatment (week 8).

The primary endpoint is the change in activation within the bilateral ventral striatum from baseline to week 8, measured as the BOLD signal during an Incentive Flanker Task using fMRI. BOLD is a signal derived from changes in blood oxygenation; in this trial, it serves as an imaging measure of activation in a brain region identified by the registry as part of the reward circuit.

Using an imaging endpoint can address a mechanistic or proof-of-concept question: whether the intervention is associated with a measurable change in a specified brain response. The ventral striatum was selected as the region of interest in the registry’s primary outcome description. The task supplies a defined context in which activation is measured, while the baseline-to-week-8 change focuses the comparison on change over the treatment period rather than a single end-of-treatment measurement.

This endpoint is not itself a direct measure of depressive symptoms or a complete assessment of clinical experience. Changes in imaging signals and changes in symptoms are distinct outcomes and may not move in parallel. The registry lists symptom and pleasure measures separately as secondary outcomes. The rationale for selecting this endpoint, details of image processing, and the exact statistical model are not reported in the registry record.

7. Results Posted in the Registry

• XEN1101: mean -0.11 versus -0.04 on control; difference -0.07 (95% CI -0.36 to 0.22), standardized effect d = -0.12; z-test p = 0.638.

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.

Change in Montgomery-Åsberg Depression Rating Scale Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • XEN1101: mean -13.01 versus -11.01 on control; difference -2.00 (95% CI -6.23 to 2.23), standardized effect d = -0.24; z-test p = 0.354.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between XEN1101 and the control. The interval gives the range of effects that remain compatible with the data.

Change in Quick Inventory of Depressive Symptomatology, Self-Report [QIDS-SR] Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • XEN1101: mean -4.79 versus -6.61 on control; difference 1.82 (95% CI -0.38 to 4.02), standardized effect d = 0.42; z-test p = 0.106.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between XEN1101 and the control. The interval gives the range of effects that remain compatible with the data.

Change in Snaith-Hamilton Pleasure Scale (SHAPS)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • XEN1101: mean -5.93 versus -4.24 on control; difference -1.69 (95% CI -5.02 to 1.64), standardized effect d = -0.26; z-test p = 0.319.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between XEN1101 and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results cover symptom severity, self-reported depressive symptoms, pleasure, and global impression. Five secondary outcomes have posted results, although the registry lists six outcome measures overall. These measures address related but distinct aspects of participants’ experience. They are not interchangeable with the primary fMRI measure of reward-circuit activation.

Across the posted secondary outcomes, the estimated changes do not point uniformly in the same direction when comparing XEN1101 with placebo. Their uncertainty intervals cross zero, and the recalculated unadjusted p-values do not by themselves establish clear between-group differences. The estimates are therefore best treated as exploratory descriptions of this trial’s outcomes rather than as confirmatory findings.

The secondary outcomes can add context to the primary result by indicating whether symptom and pleasure measures show a broadly similar pattern or a different one. But an imaging outcome and symptom scales need not agree: they measure different constructs, and a change in one does not necessarily imply a corresponding change in another. The registry record does not report a prespecified analysis linking the primary neural measure to secondary clinical measures.

Multiple outcomes create a multiplicity concern. When several comparisons are considered, some results can appear notable by chance, even if no corresponding underlying differences exist. A multiplicity adjustment or a clearly prespecified hierarchy can help control that risk, but such a procedure is not reported in the registry record. The p-values discussed for these secondary comparisons are unadjusted recalculations, so they should carry less weight than a single prespecified primary analysis with a reported statistical plan.

The secondary findings do not overturn or resolve the uncertainty in the primary comparison. Taken together, they describe varied estimates with limited precision. The registry record does not report formal analyses for these secondary outcomes, and it does not report results for one of the six listed outcome measures. Conclusions should therefore remain tied to the specific posted estimates rather than treating the set as a coherent confirmatory test of treatment effects.

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

• Change in Montgomery-Åsberg Depression Rating Scale Score
• Change in Quick Inventory of Depressive Symptomatology, Self-Report [QIDS-SR] Score
• Change in Snaith-Hamilton Pleasure Scale (SHAPS)
• Change in Temporal Experience of Pleasure Scale
• Change in Clinical Global Impression Scale

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports least-squares means and standard errors for the continuous outcomes. A mean summarizes the central value of a set of measurements. A least-squares mean is generally a model-based group mean, often adjusted for features of the analysis model; however, the registry record does not identify the covariates or model specification behind these particular estimates. The standard error describes uncertainty in an estimated mean, rather than the spread of individual participant measurements.

What does the between-group estimate represent?

The posted comparison is a mean difference for XEN1101 relative to placebo. It is calculated as the XEN1101 group estimate minus the placebo group estimate. A negative estimate means the XEN1101 group’s reported change was numerically lower than the placebo group’s reported change on that measure; a positive estimate means it was numerically higher. The estimate describes the observed contrast, not a causal effect guaranteed to apply beyond the randomized trial. Randomization supports a causal interpretation when the trial is conducted and analyzed appropriately, but details needed to assess those conditions are not all reported in the registry record.

The posted group means are least-squares means, but the recalculated contrast is an unadjusted comparison based on the posted summaries. This distinction matters: an analysis that adjusts for baseline values or other covariates can produce a different estimate and uncertainty than a simple comparison. The registry record does not report a sponsor analysis for the outcomes, so a model-based sponsor estimate cannot be compared with these recalculations.

What does a confidence interval add?

A confidence interval gives a range of values compatible with the data under the statistical method used. It conveys precision: a narrower interval indicates less uncertainty around the estimate, while a wider interval indicates more. The primary interval crosses zero, so the posted data are compatible with no mean difference as well as with differences in either direction. This does not mean that every value in the interval is equally likely, nor that the interval represents the range of individual responses.

Confidence intervals depend on the statistical assumptions and the way the estimate was calculated. The posted recalculated intervals use summary statistics; the underlying participant-level data and a full analysis model are not reported in the registry record. The intervals should therefore be read as simple, unadjusted recalculations rather than as evidence of a more complex adjusted analysis.

How should a p-value be understood?

A p-value evaluates how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the analysis assumptions were true. It is not the probability that a treatment effect exists, and it is not a measure of effect magnitude. The primary comparison has an unadjusted p-value of 0.638. The secondary unadjusted p-values are 0.354 for the Montgomery-Åsberg Depression Rating Scale, 0.106 for the QIDS-SR, and 0.319 for SHAPS. They should be interpreted alongside the estimated differences and confidence intervals, rather than as standalone verdicts.

The posted p-values and confidence intervals are recalculated from the registry’s group summaries. They do not account for any adjustment that might have been included in a sponsor analysis, because no such analyses are reported. If multiple outcomes are examined, the chance of finding an apparently unusual result somewhere among them can increase. A prespecified multiplicity procedure can address this issue, but one is not reported in the registry record.

Why does over-dispersion matter?

For continuous outcomes, variability among individual measurements affects the standard error of a group estimate and the precision of a comparison. Greater variability generally makes it harder to estimate a mean difference precisely. In other settings, such as count outcomes, over-dispersion means that observations vary more than a simple statistical model expects; a model that ignores it can understate uncertainty. The primary outcome is continuous, and the registry record does not report a model for over-dispersed data. The general point is that statistical uncertainty depends on whether the model represents the data’s variability adequately.

What limits the recalculations?

The recalculated standardized estimates and planning illustrations use assumptions described with the posted results. For standardizing a continuous mean difference, the calculations use an approximate pooled standard deviation derived from the group standard errors and participant counts. Such a conversion can help express an estimate relative to a measure of variability, but it is approximate and does not replace the original outcome scale. The underlying standard deviations and participant-level observations are not reported in the registry record.

The registry’s outcome summaries do not specify how missing measurements were handled, whether all randomized participants were included in each analysis, whether baseline values were incorporated in the model, or whether the reported standard errors account for any design features. These details can affect estimates and uncertainty. Accordingly, the recalculated comparisons are useful for understanding the posted summary statistics, but they are not a reconstruction of an unreported full statistical analysis plan.

11. Confidence Intervals and Precision

The primary mean difference is -0.07, and its confidence interval crosses zero. This means the point estimate is not precise enough to rule out either no difference or a difference in the opposite direction under the recalculation’s assumptions. The interval should be read as a range of values compatible with the data and method, not as a range containing a fixed proportion of individual participants’ outcomes.

Precision depends on the variability of the outcome and the amount of information available. The primary summary includes 29 participants in the XEN1101 arm and 31 in the placebo arm. The reported standard errors for the group means are 0.11 and 0.1. These values describe uncertainty in the estimated means, not the full distribution of individual BOLD measurements. The registry record does not report the participant-level data or the analysis details needed to assess precision under an adjusted model.

The interval for the primary comparison is wide enough to encompass estimates on both sides of zero. Thus, the posted results do not precisely identify the direction or size of a between-group difference. Lack of a clear difference in this estimate is not proof that the groups have exactly the same mean change. Conversely, the point estimate alone is not evidence of a reliable difference.

The interval and p-value are unadjusted recalculations from posted summary statistics. They should not be mistaken for results from a reported sponsor analysis. The registry record does not give an adjusted primary analysis or a detailed account of missing data, so the displayed precision does not incorporate any unreported modeling choices. The same general caution applies to the secondary outcome estimates, whose intervals also leave substantial uncertainty about the corresponding mean differences.

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 a total across both arms. They are illustrations based on the observed effect and assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect. The registry record’s own original sample-size assumptions and justification are not reported.

The 80% power column describes an assumed design in which repeated trials under the stated planning assumptions would detect the chosen effect about 80% of the time, if that effect were real and the assumptions held. The 90% power column uses a higher probability of detection under those same assumptions. These figures are design illustrations, not observed results from this trial and not a measure of the probability that the trial’s conclusion is correct.

For example, the primary outcome’s planning figures are 1,057 participants per arm for 80% power and 1,415 participants per arm for 90% power when planning for 100% of the observed effect. When planning for 75% of the observed effect, the corresponding figures are 1,879 and 2,515 participants per arm. For 50% of the observed effect, they are 4,226 and 5,657 participants per arm. The same pattern applies across the other continuous outcomes: smaller target effects require more participants per arm to achieve the same planned power.

These are sample-size planning illustrations, not observed power. They depend strongly on the observed effect used as their starting point, which can be unstable in a small trial. They should not be interpreted as the trial’s original design target or as evidence that a particular future study would necessarily achieve the stated power.

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 = -0.070; pooled standard deviation σ = 0.574.
2. n = 2 × (1.96 + 0.842)² × 0.574² / -0.070² = 1,056.4, rounded up to 1,057 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 <- -0.07                      # observed difference in means
sigma <- 0.574234122624393                     # 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(4827901)
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 = 1,057 (80% power), 1,415 (90% power)
 75% of observed effect: n per arm = 1,879 (80% power), 2,515 (90% power)
 50% of observed effect: n per arm = 4,226 (80% power), 5,657 (90% power)
power.t.test: 1057.3 
Simulated power at n = 1,057 per arm: 0.802 (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

The registry lists a primary imaging outcome and several secondary outcomes, but it does not report how the analyses were prioritized or whether any procedure was planned to account for multiple comparisons. When researchers test multiple outcomes, the probability of at least one apparently unusual result can rise. Methods such as adjusting significance thresholds or defining an ordered testing strategy can address multiplicity, but the registry record does not say whether such methods were used.

The posted secondary p-values are unadjusted recalculations. They should not be read as if each were the only outcome tested, and they do not establish confirmatory evidence on their own. The primary outcome remains the principal endpoint named in the record, but the record does not provide a detailed analysis plan against which to assess whether the posted results follow a prespecified hierarchy.

Missing-data handling is also not reported in the registry record. The outcome summaries include 29 participants for XEN1101 and 31 for placebo, but the record does not explain whether these counts represent all randomized participants, participants with available week-8 measurements, or a specified analysis population. It does not describe imputation, exclusions, or sensitivity analyses. Without those details, it is not possible to assess whether missing measurements could have affected the estimates.

The registry record does not identify an intention-to-treat, per-protocol, or other analysis population, nor does it report a detailed statistical analysis plan. It also does not describe interim analyses. These omissions do not demonstrate that such procedures were absent; they mean the relevant information is not reported in the registry record. As a result, the posted summary statistics can be interpreted descriptively, but important features of the planned and implemented analyses cannot be independently assessed from this record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fainting (3.4%).

The registry reports serious adverse events among 1 of 29 participants in the XEN1101 group and 0 of 31 participants in the placebo group. Fainting is the top-listed serious adverse event term, reported as 3.4%. Deaths are reported as 0 in both groups. The registry also reports other adverse events for 27 of 29 participants assigned to XEN1101 and 25 of 31 assigned to placebo.

These figures are counts and a listed percentage, not a full description of event timing, severity, recurrence, or relationship to treatment. The registry record does not provide a detailed account of how events were collected or adjudicated. With these group sizes, the counts describe the reported events in this trial but provide limited information about less common events or differences in risk. The figures should be read as safety reporting from this study, not as a complete assessment of safety.

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

The posted results describe a randomized comparison of XEN1101 and placebo in a phase 2 trial with 60 enrolled participants. For the primary fMRI outcome, the recalculated mean difference is -0.07, and the confidence interval crosses zero. The estimate is uncertain and does not establish a clear between-group difference in the measured change in ventral striatum activation. It also does not establish that the groups had identical outcomes.

The endpoint is a BOLD signal during a specified task, not a direct measure of depressive symptoms or an overall judgment of clinical benefit. The secondary outcomes provide separate measures of symptoms and pleasure, but their estimates are also exploratory and imprecise. The registry record does not report a multiplicity strategy or a full statistical analysis plan, which limits the strength of conclusions drawn from multiple outcome comparisons.

These results cannot establish that XEN1101 does or does not improve depression, and they do not support medical decisions. They address the outcomes posted for this particular trial and do not answer every question about efficacy, safety, mechanism, durability, or how findings might apply to other people. The registry record does not report enough detail about missing data, analysis populations, or model specification to fully evaluate the estimates.

A null-compatible interval is not evidence that no effect exists. It indicates that the data and method leave considerable uncertainty about the magnitude and direction of the mean difference. Likewise, the observed point estimate should not be treated as a definitive measure of a true effect. Further interpretation would depend on the full trial report, participant-level analyses, and prespecified methods, none of which are reported in the registry record.

17. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is a neuroimaging measure linked by the registry to reward-circuit activation, while its secondary outcomes include symptom and pleasure scales. Distinguishing those constructs matters: evidence about a neural signal is not automatically evidence about symptom change, and results across different outcome types may not align.

The record also illustrates why an estimate and its uncertainty should be considered together. The primary comparison is -0.07, but the interval crosses zero and the unadjusted p-value is 0.638. The point estimate alone gives little information about precision; the interval indicates that the data are compatible with a range of possible differences. A non-small p-value does not prove there is no difference, just as an estimated difference does not prove a reliable effect.

The study is described as proof of concept, with 60 participants enrolled. The planning illustrations based on the observed effects indicate that substantially larger per-arm numbers would be required under the stated assumptions to detect smaller effects with the specified power. Those calculations are not the trial’s original design rationale and are not observed power. They demonstrate how limited precision and small target effects can make planning consequential.

Finally, the registry record contains outcome summaries but does not report key analysis details, including multiplicity handling, missing-data methods, and analysis populations. That gap makes transparent reporting important: a reader needs those details to distinguish exploratory summary comparisons from prespecified confirmatory tests. The posted data can still be interpreted, but the scope of a defensible statistical conclusion is constrained by what the record documents.

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 endpoint is an fMRI BOLD measure during a task, and the record does not provide details on image acquisition, preprocessing, quality control, region-of-interest definition beyond the bilateral ventral striatum, or statistical modeling. Those details matter when interpreting imaging estimates because measurement and analysis choices can affect both estimates and uncertainty.

The registry reports least-squares means and standard errors but does not identify the model behind them. The recalculated comparisons use posted summaries and are unadjusted. They may not reproduce a planned adjusted analysis, and the record does not provide participant-level data with which to check the calculations or assess assumptions.

The posted outcome counts are 29 for XEN1101 and 31 for placebo, but the registry does not explain the relationship between these counts and the randomized population, or report the handling of missing measurements. It does not identify the analysis populations or provide sensitivity analyses. The record also does not report a detailed multiplicity strategy despite multiple outcomes, including five secondary measures with posted results.

Finally, the registry identifies a phase 2 proof-of-concept trial but does not report its original sample-size justification, interim-analysis plan, or full protocol analysis plan. These are specific limits on interpreting this record, rather than evidence that the procedures were not conducted. The reported results therefore support a description of the posted outcomes, while leaving important questions about the analysis and the robustness of estimates unresolved.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: XEN1101 for Major Depressive Disorder — NCT04827901.
• Registry record last updated 2026-11-06; status last verified 2025-03.
• Results first posted 2026-11-06.
• 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

The registry record describes a completed, randomized, quadruple-masked, parallel-group phase 2 trial of XEN1101 versus matching placebo for major depressive disorder. Enrollment was 60. XEN1101 was given as two 10 mg capsules daily for eight weeks, for a total daily dose of 20 mg; placebo was taken daily for eight weeks.

The primary outcome was change from baseline to week 8 in bilateral ventral striatum activation during an Incentive Flanker Task, measured by fMRI BOLD signal. The posted group summaries include 29 participants for XEN1101 and 31 for placebo. The recalculated unadjusted mean difference is -0.07, with p = 0.638 and a confidence interval crossing zero.

Five secondary outcomes have posted results. The record does not report a full statistical analysis plan, missing-data methods, analysis populations, or multiplicity procedures. Safety summaries report 1 serious adverse event in the XEN1101 group and 0 in the placebo group, with 0 deaths in either group.