A Study to Assess the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects With DSM-5 Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects With DSM-5 Schizophrenia (NCT05919823), a randomized phase 3 study. The primary outcome is Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 5 of the Double-Blind Period.

2. Clinical Question

The clinical question is limited to the double-blind comparison. The study also included a 12-week open-label extension, but outcomes from that period do not provide the same randomized comparison because participants received open-label KarXT. The primary result therefore concerns the posted Week 5 comparison, not the longer-term extension or every clinical outcome that might matter to patients and clinicians.

3. Trial Design

The registry describes a Phase 3, multicenter, randomized study with a 5-week double-blind part followed by a 12-week open-label extension. In the double-blind part, participants were assigned in parallel to KarXT or placebo. The registry labels masking as triple and the model as factorial; further details about the masking roles or factorial factors are not reported in the registry record. The study status is completed.

The registry records enrollment of 202. It lists the study start as 2023-05-29 and primary completion as 2024-09-16. The population of interest was acutely psychotic hospitalized Chinese adults with DSM-5 schizophrenia. The primary endpoint was change from baseline in PANSS total score at Week 5 of the double-blind period. The primary outcome population was defined as randomized participants who received at least one dose and had baseline and at least one post-baseline PANSS assessment in that period.

The posted primary endpoint results include 99 participants in the KarXT arm and 97 in the placebo arm. Those are the group sizes reported for this endpoint, not a statement that every enrolled participant contributed to the endpoint analysis. The registry lists xanomeline and trospium chloride capsules and placebo as the interventions. Dose details, the original sample-size justification, and further allocation procedures are not reported in the registry record.

The open-label extension followed the randomized period and is described as 12 weeks long. Its presence adds a period of follow-up, but it does not extend the blinded placebo comparison. The registry lists two open-label sequences in its safety results, KarXT/KarXT and Placebo/KarXT; details of the transition rules and the number who entered the extension are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Participants completed 5-week KarXT treatment in the double-blind period and signed ICF for the open-label extension period continued KarXT treatment to additional 12-week.

Pre-Treatment Period

Reasons for not completing this period:

Double-Blind Period

Reasons for not completing this period:

Open Label Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least one dose of study medicine and had baseline and least 1 post-baseline PANSS assessment in the double-blind period. Prespecified to be reported for the double-blind period only.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Open-Label participants are accounted for under their Double-Blind Groups

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 5 of the Double-Blind Period, measured over At Baseline and at Week 5 of the Double-Blind Period.

The primary endpoint is change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 5 of the double-blind period. PANSS is a clinical rating scale used to measure symptom severity in schizophrenia. It includes 30 items across positive symptoms, negative symptoms, and general psychopathology. Each item is rated from 1, absent, to 7, extreme, and the total score can range from 30 to 210. Higher total scores indicate more severe symptoms and worse clinical outcomes.

Change from baseline describes how the score at follow-up differs from the baseline assessment. The registry defines baseline as the last non-missing assessment before the first dose of study drug. A negative change therefore represents a reduction in the score, while a positive change would represent an increase. The endpoint is useful for comparing average symptom-score changes between randomized groups over the double-blind period. It does not, by itself, describe every symptom domain separately, the experience of each individual participant, or outcomes beyond the measured time point.

The registry reports least-squares mean changes for each group and a least-squares mean difference between groups. Least-squares means are model-based group estimates rather than simple descriptions of each individual’s response. Standard errors describe uncertainty around the group estimates; the reported confidence interval for the between-group difference provides a range of values compatible with the analysis and its assumptions.

7. Results Posted in the Registry

• Double-Blind Part: KarXT: mean -16.90 versus -7.70 on control; difference -9.20 (95% CI -15.02 to -3.38), standardized effect d = -0.44; z-test p = 0.002.

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 From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period

• 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:
  • Double-Blind Part: KarXT: mean -6.50 versus -4.60 on control; difference -1.90 (95% CI -3.86 to 0.06), standardized effect d = -0.27; z-test p = 0.057.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Double-Blind Part: KarXT and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period

• 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:
  • Double-Blind Part: KarXT: mean -3.20 versus -0.70 on control; difference -2.50 (95% CI -4.32 to -0.68), standardized effect d = -0.38; z-test p = 0.007.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Double-Blind Part: KarXT than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period

• 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:
  • Double-Blind Part: KarXT: mean -3.10 versus -0.50 on control; difference -2.60 (95% CI -4.45 to -0.75), standardized effect d = -0.39; z-test p = 0.006.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Double-Blind Part: KarXT than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes spanning PANSS positive and negative symptom scores, the negative Marder factor, clinical global severity, response status, and outcomes during the open-label period. Detailed double-blind comparisons are posted for three Week 5 PANSS measures: positive symptoms, negative symptoms, and the negative Marder factor. Their estimated changes and between-group comparisons generally point in the same direction as the primary PANSS total-score result. The registry also lists outcomes for which detailed numerical comparisons are not reported in the registry record.

These measures provide additional views of symptoms rather than independent confirmation of the whole primary finding. PANSS total score combines several symptom domains, while the secondary scores focus on particular domains or related constructs. The secondary outcomes can help describe the pattern of the primary endpoint, but they do not replace it. Open-label outcomes also have a different interpretive status from the randomized double-blind comparison.

The reported secondary analyses include p-values that are unadjusted in the summary-statistic recalculations. When multiple outcomes are tested, the chance of at least one apparently notable result can increase. Unless a multiplicity strategy is reported, individual secondary p-values should therefore be treated as exploratory evidence rather than as definitive confirmatory tests. The registry does not report how multiplicity across the outcomes was handled, so the weight given to individual secondary results should remain limited.

The registry record lists 24 secondary outcomes, but not all have detailed numerical results in the posted analysis information. For outcomes without reported numerical comparisons, their direction, magnitude, and precision are not reported in the registry record. This limits any attempt to describe the full secondary-outcome pattern.

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

• Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period
• Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period
• Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period
• Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 5 of the Double-Blind Period
• Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 5 of the Double-Blind Period
• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 12 of the Open-Label Period
• Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period
• Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period

9. Statistical Interpretation

10. Statistical Methods Explained

What does the reported mean represent?

The primary result is expressed as a least-squares mean change for each arm and a least-squares mean difference between arms. A mean is a summary of the group’s average outcome. A least-squares mean is estimated within a statistical model and may differ from a simple arithmetic average, depending on the model and the data used. The registry identifies the reported comparison as coming from a mixed model repeated measure analysis. The model’s full specification, including covariates and any additional assumptions, is not reported in the registry record.

The arm estimates, -16.9 for KarXT and -7.7 for placebo, are changes from baseline. The between-group estimate, -9.2, compares those modeled changes. A negative between-group difference means the modeled change was more negative in the KarXT group. In the context of PANSS, where higher scores indicate more severe symptoms, a more negative change represents a larger average score reduction. The estimate applies to the group comparison and does not establish that all participants had the same experience.

Why use a repeated-measures model?

General explanation: repeated-measures methods are used when outcomes are collected over time from the same participants. Measurements from one person tend to be related, so treating each measurement as if it came from a different person can misrepresent uncertainty. A mixed model can account for the repeated structure and use information from multiple scheduled assessments, depending on how it is specified. The registry names a mixed model repeated measure method for the primary analysis, but does not report enough detail to reconstruct its full specification.

The posted primary endpoint is at Week 5, while the model name indicates repeated measurements were part of the analysis. The registry does not report which visits were included in the model, its covariance structure, or the assumptions used for missing observations. Those details should not be inferred from the method label alone.

What does the standard error tell the reader?

The registry reports standard errors for the arm-level least-squares means: 2.122 for KarXT and 2.074 for placebo. A standard error describes the estimated uncertainty in a group mean, rather than the spread of individual participant scores. It is not interchangeable with a standard deviation. The registry’s arm-level records do not include confidence limits for those means.

General explanation: standard errors become smaller when an estimate is more precise, all else being equal. They are used in statistical inference, including the calculation of confidence intervals and tests. They do not describe how much participants differ from one another. The registry’s posted comparison has its own reported confidence interval, which is the more direct summary of precision for the between-group estimate.

How should the recalculation be understood?

The posted recalculated comparison is a simple unadjusted calculation from the group summaries. It gives a mean difference of -9.2, a 95% interval from -15.02 to -3.384, and an unadjusted p-value of 0.002. The standard deviation used in that calculation is approximate, as indicated in the calculation record. This approach does not reproduce the sponsor’s mixed model repeated measure analysis, which is based on the trial’s analysis method and may incorporate information beyond the summary statistics used in the recalculation.

General explanation: an unadjusted calculation can be a useful check on whether the reported group summaries and broad direction of the result are coherent. It is less informative than the prespecified model when the trial’s analysis accounts for repeated observations or other features not represented by the summaries. The recalculation is therefore a secondary statistical check, not a replacement for the registry’s reported analysis.

What does a p-value add?

A p-value assesses how compatible the observed data are with a specified null hypothesis under the statistical model. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The recalculated unadjusted p-value is 0.002. The registry’s reported primary analysis gives a p-value of 0.001, which is not repeated numerically because it has more than three decimal places. Both the estimate and confidence interval are important to interpretation; a p-value alone does not show the range of plausible effects.

General explanation: statistical significance is influenced by the estimated effect, its precision, the analysis model, and the assumptions used. It should be interpreted with the magnitude and uncertainty of the estimate, the endpoint’s meaning, the study design, and the completeness of reporting. A statistically significant result does not on its own establish clinical importance, nor does it resolve concerns about missing data or multiple outcome testing.

11. Confidence Intervals and Precision

The primary reported 95% confidence interval for the least-squares mean difference runs from -14.8 to -3.6. It lies entirely below zero, so the reported analysis is compatible with a greater average reduction in PANSS total score in the KarXT group than in the placebo group. The interval gives a range of estimates consistent with the data and model, not a range containing a stated proportion of individual participant outcomes.

The recalculated unadjusted interval runs from -15.02 to -3.384. It is close to the sponsor-reported interval, though the endpoints are not identical. The recalculation relies on posted summaries and an approximate pooled standard deviation; the reported analysis uses a mixed model repeated measure method. The methods differ, so small differences in interval limits are not unexpected. The registry does not flag a discrepancy.

General explanation: a confidence interval communicates both the direction and precision of an estimate. A narrower interval indicates greater precision under the analysis assumptions, while a wider interval indicates more uncertainty. An interval that excludes zero is consistent with a nonzero difference at the corresponding confidence level, but it does not establish the effect’s clinical importance or the validity of every modeling assumption.

The interval is for the average between-group effect at the primary time point, not for the treatment effect in every subgroup or for outcomes during the open-label period. Subgroup-specific estimates and their precision are not reported in the registry record. The confidence interval also does not address uncertainty from unreported aspects of the analysis plan, missing-data handling, or multiplicity.

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 events. They are illustrations based on the observed primary effect and use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect to detect is the stated fraction of the observed effect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

For planning around 100% of the observed effect, the illustrations give 81 participants per arm for 80% power and 108 participants per arm for 90% power. For 75% of the observed effect, they give 143 participants per arm for 80% power and 191 participants per arm for 90% power. For 50% of the observed effect, they give 321 participants per arm for 80% power and 429 participants per arm for 90% power.

In plain terms, the 80% power column describes the number of participants per arm estimated to give an 80% chance of detecting the chosen effect under the stated planning assumptions, if that effect is present. The 90% column applies the same idea at a higher target probability. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants per arm.

These are planning illustrations, not observed power. They do not establish what the trial’s investigators planned or why they selected the enrollment target. The registry does not report the original design assumptions, and these calculations should not be treated as a retrospective measure of the trial’s ability to detect an effect.

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 = -9.200; pooled standard deviation σ = 20.776.
2. n = 2 × (1.96 + 0.842)² × 20.776² / -9.200² = 80.1, rounded up to 81 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 <- -9.2                      # observed difference in means
sigma <- 20.776464316253                     # 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(5919823)
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 = 81 (80% power), 108 (90% power)
 75% of observed effect: n per arm = 143 (80% power), 191 (90% power)
 50% of observed effect: n per arm = 321 (80% power), 429 (90% power)
power.t.test: 81 
Simulated power at n = 81 per arm: 0.796 (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. Analyses Reported by the Sponsor

The registry’s sponsor-reported primary analysis used a mixed model repeated measure method and reported a least-squares mean difference of -9.2, with a 95% confidence interval from -14.8 to -3.6. The registry labels the analysis as superiority. The reported p-value is 0.001; stated without its extra decimal places, it is below 0.01.

The simple unadjusted recalculation from the posted summary statistics also estimates a difference of -9.2. Its 95% interval is -15.02 to -3.384, and its unadjusted p-value is 0.002. Thus, the central estimate and overall direction are consistent across the sponsor’s model-based result and the summary-statistic check. Their confidence intervals are similar but not identical.

The methods are not interchangeable. The recalculation is based on posted group summaries and an approximate pooled standard deviation, while the sponsor’s reported analysis is the mixed model repeated measure analysis. The latter is the trial’s registry-reported analysis and is the primary result for interpretation. The record does not flag a discrepancy between the posted result and the recalculation. The recalculation is best understood as a check on the broad numerical pattern, not as a correction or replacement of the sponsor’s analysis.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified as PANSS total-score change at Week 5, and the registry specifies an analysis population: randomized participants who received at least one dose of study medicine and had baseline and at least one post-baseline PANSS assessment in the double-blind period. The registry states that the primary endpoint was prespecified for the double-blind period only. These details help define which endpoint and participants the primary result concerns.

The registry record does not report a full statistical analysis plan, including the complete model specification, the handling of missing outcome measurements, or whether sensitivity analyses were conducted. It also does not report how multiplicity across the primary and secondary outcomes was controlled. These absences do not establish that such procedures were not used; they mean that they are not reported in the registry record.

Missing-data handling matters because participants may not have every planned assessment. A repeated-measures model can use observed measurements under assumptions about the data that are not fully described by the method name. Without information about the assumptions, imputation or likelihood procedures, and sensitivity analyses, readers cannot assess how dependent the result may be on the approach to missing observations. The defined primary analysis population excludes participants without the specified baseline and post-baseline assessments, but the registry does not give further details on missingness patterns or their treatment.

Multiplicity matters because the registry lists many secondary outcomes. Testing multiple endpoints can increase the chance of at least one result appearing statistically notable by chance. The posted secondary p-values should therefore be interpreted cautiously in the absence of a reported adjustment or testing hierarchy. The registry does not provide enough information to determine whether a formal multiplicity procedure was part of the original analysis.

16. 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: schizophrenia (7.1%), completed suicide (3.6%), suicidal ideation (3.6%), spinal compression fracture (1.0%).

For the double-blind period, the registry reports serious adverse events in 0 participants among 102 at risk in the KarXT group and 3 among 98 at risk in the placebo group. In the open-label period, it reports 0 among 38 at risk in the KarXT/KarXT group and 3 among 28 at risk in the Placebo/KarXT group. These are descriptive counts for the listed groups and periods. The open-label groups should not be treated as a randomized placebo comparison.

The registry reports no deaths in either double-blind group and no deaths in the KarXT/KarXT open-label group. It reports 1 death in the Placebo/KarXT group. The record does not provide enough information to infer the relationship of that death or any serious event to study treatment. The registry lists serious-event terms and percentages, including schizophrenia at 7.1%, completed suicide at 3.6%, suicidal ideation at 3.6%, and spinal compression fracture at 1.0%. The denominator and detailed event context for those term percentages are not reported in the registry record.

Serious adverse-event counts are not a complete summary of safety. They do not show the full range, duration, severity, or treatment relatedness of events, and small counts can be imprecise. The registry also reports other adverse events, but these counts should be interpreted separately from serious events. A comparison of safety profiles requires the relevant event definitions, exposure, follow-up, and attribution details, some of which are not reported in the registry record.

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

The posted primary result shows a greater average reduction in PANSS total score at Week 5 in the KarXT group than in the placebo group, according to the registry’s mixed model repeated measure analysis. The estimated difference is -9.2, and its reported 95% confidence interval ranges from -14.8 to -3.6. The interval does not include zero, and the registry labels the analysis as superiority. This describes the statistical result for the defined endpoint and population.

It does not mean that every participant experienced a reduction, that every participant had the same response, or that the average difference guarantees a particular outcome for an individual. It does not by itself establish the clinical importance of the difference. The registry record does not provide a threshold for interpreting the size of a PANSS change as clinically important, so such a judgment cannot be made from these statistics alone.

The result is specific to the 5-week double-blind comparison in the studied population. It does not directly establish what happened beyond that period, because the subsequent 12-week extension was open-label. Nor does the primary result answer every question about symptoms, functioning, tolerability, or longer-term outcomes. Secondary measures add context but carry less weight when multiplicity procedures are not reported.

The safety counts also require caution. Serious adverse events and deaths are reported for the study groups, but the registry’s figures do not establish whether an event was caused by the intervention. The open-label results cannot be read as a randomized comparison. Taken together, the record supports a statistical description of the primary outcome and selected safety observations; it does not support broader conclusions that go beyond the reported design, measurements, follow-up, and analysis details.

18. Why This Trial Matters Statistically

This study illustrates how a registry result can be read by connecting the clinical scale, the modeled group estimates, and the uncertainty around the comparison. The PANSS total score measures symptom severity, so the direction of change matters: a more negative change represents a greater average score reduction. The between-group estimate and its confidence interval make that contrast explicit without implying that every participant had the same response.

It also shows why the sponsor’s model-based analysis and a simple recalculation should be distinguished. Both give a central difference of -9.2, but the recalculation relies on summary statistics and an approximate standard deviation, whereas the registry reports a mixed model repeated measure analysis. Agreement in the broad pattern is reassuring as a consistency check, but it does not make the methods equivalent or eliminate uncertainty about unreported model details.

The trial’s two-part design is important to interpretation. The randomized placebo comparison belongs to the 5-week double-blind period. The open-label extension adds follow-up but is not a continuation of the blinded placebo contrast. Keeping those periods separate avoids treating unlike comparisons as if they answered the same question.

Finally, the record demonstrates why statistical significance is only one part of evidence assessment. Precision, population definition, missing-data methods, multiplicity, and the clinical meaning of the scale change all affect interpretation. Some of these details are not reported in the registry record. Identifying those limits is part of reading the result accurately, rather than a reason to infer information the record does not contain.

19. 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 limited to the Week 5 endpoint in the double-blind period and the registry-defined analysis population. It should not be generalized automatically to the open-label extension, other populations, or other time points. The study population was acutely psychotic hospitalized Chinese adults with DSM-5 schizophrenia; the registry result does not establish how estimates would apply to populations with different characteristics or care settings.

The registry labels the design factorial and triple-masked, but details of the factorial factors and the specific roles masked are not reported in the registry record. The model’s full specification, covariates, repeated-measures structure, missing-data assumptions, and sensitivity analyses are also not reported. The primary endpoint population is described, but the flow of participants through assessments and reasons for missing data are not available in the posted information.

The trial’s original sample-size assumptions and justification are not reported. Planning illustrations based on the observed effect cannot reveal what investigators intended when designing the study. Multiplicity handling across the many secondary outcomes is likewise not reported, which limits confirmatory interpretation of those results.

The registry lists serious adverse-event counts and selected event terms, but the details needed to evaluate event timing, treatment relatedness, and exposure are not reported in the registry record. The open-label safety groups are descriptive and do not provide a concurrent randomized comparison. These limitations do not change the reported primary estimate, but they constrain the conclusions that can be drawn from the record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Assess the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects With DSM-5 Schizophrenia — NCT05919823.
• Registry record last updated 2025-12-17; status last verified 2025-12.
• Results first posted 2025-11-21.
• 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.

23. Record Summary

The registry record describes a completed Phase 3 randomized study of KarXT versus placebo in acutely psychotic hospitalized Chinese adults with DSM-5 schizophrenia. Its double-blind part lasted 5 weeks and was followed by a 12-week open-label extension. Enrollment was 202; the recorded start date was 2023-05-29 and primary completion date was 2024-09-16.

The primary endpoint was change from baseline in PANSS total score at Week 5. The sponsor-reported mixed model repeated measure analysis estimated a least-squares mean difference of -9.2, with a 95% confidence interval from -14.8 to -3.6. The result is specific to the defined endpoint, analysis population, and double-blind comparison. The registry also lists secondary outcomes and safety results, while several analysis and reporting details—including multiplicity and missing-data methods—are not reported in the registry record.