An Open-label Study to Assess the Long-term Safety, Tolerability, Effectiveness, and Durability of Effect of KarXT in Patients With DSM-5 Diagnosis of Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-label Study to Assess the Long-term Safety, Tolerability, Effectiveness, and Durability of Effect of KarXT in Patients With DSM-5 Diagnosis of Schizophrenia (NCT05643170), a na phase 3 study. The primary outcome is The Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation.

2. Clinical Question

The study was intended to follow participants over a planned three-year period. Its primary endpoint is a count of participants, not a measure of change in symptoms or a comparison between treatments. The registry record does not report a numerical result for this endpoint, so it cannot show how many participants discontinued because of treatment-emergent adverse events. Safety counts elsewhere in the record describe serious and other adverse events; they should not be mistaken for the primary discontinuation endpoint. With no comparator group and no reported primary endpoint result, the record supports a description of the study and its listed safety data, but not an estimate of a treatment effect relative to another option.

3. Trial Design

This is a Phase 3 study described as open-label, multicenter, and single-group. It enrolled participants with schizophrenia and evaluated KarXT, identified as xanomeline and trospium chloride capsules. The registry lists allocation as not applicable and masking as none. These design features mean the record does not describe random assignment to distinct treatment groups or masking of participants and investigators.

The brief summary describes a planned three-year study for participants whose current medication was not well tolerated and/or whose clinical symptoms were not well controlled. It says participants would be switched to KarXT. The record lists a start date of 2022-11-08, a primary completion date of 2023-03-01, enrollment of 4, and a terminated status. The reason for termination and the duration each participant actually received treatment are not reported in the registry record. The planned study duration should therefore not be read as the observed follow-up period for every participant.

The primary objective included long-term safety and tolerability and assessment of effectiveness, persistence, and durability of effect using the Investigator Assessment Questionnaire and Clinical Global Impression - Severity of Illness scale. Secondary objectives included further effectiveness assessment with the Clinical Global Impression - Improvement scale, continued safety and tolerability assessment, and additional patient scales and assessments. The registry lists seven outcome measures and no analyses. It does not report a statistical analysis plan, the planned timing of individual assessments, or how the listed objectives were prioritized beyond identifying the primary endpoint.

Because this is not a randomized comparison, its findings are descriptive of the participants treated in this study. Changes over time, if recorded, would not by themselves separate treatment effects from natural variation, concurrent care, expectations in an open-label study, or other influences. The registry record also does not report a control group or a basis for comparing KarXT with another treatment.

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: All treated participants

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 The Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation, measured over From first dose to 28 days post last dose (up to approximately 113 days).

The primary endpoint is the number of participants with treatment-emergent adverse events leading to discontinuation. It is measured from the first dose through 28 days after the last dose, for up to approximately 113 days. The registry defines an adverse event as a symptom, physical sign, syndrome, or disease that begins during the study or, if present at screening, worsens during the study, regardless of whether it is suspected to be caused by the event.

This endpoint combines two clinically relevant events in the study record: an adverse event occurring or worsening during the specified observation period, and discontinuation attributed to that event. Counting affected participants gives a direct description of how often this particular outcome occurred among treated participants. It does not capture every adverse event, nor does it measure the intensity, duration, or total number of events. A participant may have an adverse event without discontinuing, and an event count is not interchangeable with a count of participants.

The endpoint is useful for describing treatment tolerability in the study because discontinuation indicates that an adverse event was associated with stopping study treatment. It is not a standalone measure of overall safety, and it does not establish that treatment caused an event. The record identifies all treated participants as the endpoint population, but does not report a numerical result for the primary endpoint. The safety figures listed elsewhere should not be substituted for that missing result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help define what an estimate describes, how uncertain it is, and whether a comparison is supported by the design. In this record, the central interpretive point is that the study is single-group and open-label. The listed safety counts are descriptive, and the registry reports no analyses. Methods used for a formal inferential analysis are not reported in the registry record.

What does a count of participants describe?

The primary endpoint is a count: participants with treatment-emergent adverse events leading to discontinuation. A count answers how many participants met the endpoint in the specified population and observation period. It is not a rate per unit of time, a count of all adverse events, or a measure of symptom improvement. The endpoint population is listed as all treated participants. The registry record does not state a numerical result for this endpoint, so no endpoint estimate can be interpreted.

Safety reporting often distinguishes participants who experienced at least one event from the total number of events. These quantities answer different questions. A participant may experience more than one event, while a participant count counts that person once for the relevant category. The posted safety figures are labeled as numbers of participants affected. They should not be read as the total number of event episodes. The record does not give enough information to reconstruct event-level patterns, timing, duration, or severity for every event.

Why does the study design matter?

A single-group study can describe outcomes among people who received the intervention, but it does not supply an internal randomized control for estimating what would have happened under a different treatment. General statistical principle: a comparison is more informative about treatment effects when groups are made comparable by design, and randomization is one way to address differences that could otherwise influence outcomes. Here, allocation is listed as not applicable and the study is open-label. Thus, the registry's safety counts cannot establish that KarXT caused or prevented an event, nor can they quantify a difference from another treatment.

Open-label status can be relevant to both reporting and assessment. General statistical principle: when people know the treatment being received, expectations can influence subjective reports, clinical judgments, and decisions to stop treatment. This consideration is especially relevant to scales assessed by investigators or participants. It does not prove that a particular reported outcome was biased; it is a limitation to consider alongside the lack of a comparator.

What can uncertainty measures tell readers?

A confidence interval is a statistical range used to express uncertainty around an estimate under specified assumptions. General statistical principle: narrower intervals indicate greater precision, while wider intervals indicate that a range of values remains compatible with the data and method. The registry record does not report confidence intervals for the safety counts or the primary endpoint. With sparse observations, estimates can be imprecise; a count alone does not communicate the range of uncertainty that would accompany a formal estimate.

Tests of statistical significance and effect estimates also require a defined analysis and an appropriate comparison or reference value. No analyses are listed in the registry record. No p-value, adjusted estimate, or comparative result should be inferred from the participant counts. In particular, the absence of a reported statistical test is not evidence that an outcome was or was not statistically significant.

How should planning illustrations be read?

Any sample-size figures associated with the posted results are planning illustrations computed from an observed effect, not the trial's own design or an analysis of observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. For time-to-event calculations, the stated convention is to report a total number of events; other calculations report participants per arm. These assumptions are not a description of this single-group trial, and they do not turn its results into a randomized comparison. A planning illustration is conditional on its assumptions and is not evidence that the study had a particular probability of detecting an effect.

General statistical principle: over-dispersion occurs when count data vary more than a chosen statistical model expects. If present, a model that assumes less variability may understate uncertainty. The registry record does not report a count model or an assessment of over-dispersion, so no conclusion about either can be drawn for this study. More broadly, because no statistical analysis plan or inferential analysis is reported, readers should treat the posted numerical safety entries as descriptive registry data rather than as the output of a documented comparative model.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("KarXT")
n      <- c(4)
events <- c(1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  KarXT  4  1  25.0  0.6  80.6  4.6  69.9  5.3  71.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and no analyses. The primary outcome is the number of participants with treatment-emergent adverse events leading to discontinuation; other listed objectives include safety outcomes, the Clinical Global Impression - Improvement score, the Medication Satisfaction Questionnaire score, and additional scales described in the study summary. The registry record does not report a statistical plan explaining how these outcomes were to be analyzed or prioritized beyond identifying a primary endpoint.

Multiplicity refers generally to the interpretive issue that can arise when many outcomes or statistical tests are examined. If multiple tests are conducted, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. This is a general statistical concern, not a claim that the study conducted multiple tests. No analyses are listed, and methods for controlling or otherwise interpreting multiplicity are not reported in the registry record.

Missing-data methods are also not reported in the registry record. The record does not state how missing assessments, withdrawal, incomplete follow-up, or unavailable outcome measurements were handled. It also does not report how many participants contributed data to each outcome. The primary endpoint population is listed as all treated participants, but that alone does not specify the analysis set or handling of missing information for every outcome.

These omissions limit reproducibility and interpretation. Without analysis details, readers cannot determine whether the posted entries reflect a prespecified analysis, how incomplete observations were treated, or whether outcome-specific populations differed. The terminated status makes it particularly important not to assume that planned long-term assessments were completed. The reason for termination and the extent of missing follow-up are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: schizophrenia (25.0%).

The registry lists the KarXT group with 4 participants at risk in the serious-event category and 1 affected. In the other-event category, it lists 4 at risk and 3 affected. Deaths are listed as 0. The record also names schizophrenia at 25.0% among the top serious terms. These figures describe the registry's safety entries and should be read as counts of participants, not counts of individual event episodes.

The serious and other categories are not the primary endpoint. The primary endpoint specifically counts participants with treatment-emergent adverse events leading to discontinuation, and its numerical result is not reported in the registry record. The safety figures therefore cannot be used to infer how many participants discontinued because of an adverse event.

General statistical principle: a serious adverse event category is not the same as a rating of symptom intensity. Seriousness generally concerns outcomes such as substantial consequences or required intervention, while severity describes how intense an event is. The registry figures do not provide individual event narratives or enough detail to assess event timing, severity, relationship to treatment, or whether a participant appears in more than one category. The small group and lack of a comparator also mean these counts do not estimate a comparative risk.

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

The posted record establishes that a Phase 3, open-label, single-group study of KarXT enrolled 4 participants and is listed as terminated. It provides descriptive safety entries: 1 participant affected in the serious-event category, 3 in the other-event category, and 0 deaths. Schizophrenia is listed at 25.0% among the top serious terms. These observations describe the registry record, not a comparison against another treatment.

The record does not report a numerical result for the primary endpoint, which concerns treatment-emergent adverse events leading to discontinuation. It also lists no analyses. Consequently, the posted data do not establish a primary endpoint frequency, a statistical estimate of uncertainty for that endpoint, or a treatment effect relative to a comparator. The serious and other adverse-event entries cannot fill that gap because they describe different categories.

The study's objectives include long-term safety, tolerability, effectiveness, persistence, and durability of effect. The brief summary describes a planned three-year study, but the record does not report the follow-up actually achieved by each participant or the reason the study was terminated. It would be inappropriate to assume that the planned duration was completed or that long-term objectives were adequately assessed.

More broadly, an uncontrolled, open-label study can document what occurred among participants receiving the intervention, but it cannot separate treatment effects from other influences as a randomized comparison might. The record does not show that treatment caused the listed events or that it prevented other outcomes. The findings should be interpreted as limited descriptive observations from the registry, not as evidence for a comparative benefit, harm, or long-term effect.

14. Why This Trial Matters Statistically

This study matters statistically because it illustrates the difference between a study objective and a reported result. The registry describes a primary endpoint focused on adverse events leading to discontinuation, but does not report its numerical outcome. It also lists no analyses. Readers therefore need to keep the stated research question separate from the safety counts that are actually posted.

The design is also important. A single-group, open-label study can contribute descriptive information about participants receiving KarXT, but it lacks a randomized control group for estimating comparative effects. This is not a minor technical detail: it defines what the data can answer. Counts in a treated group do not reveal what would have occurred under a different treatment or without study treatment.

Enrollment of 4 makes precision a central concern for interpretation. Sparse participant counts can be informative as a record of observed events, but provide limited information about how often outcomes might occur in a broader population. A zero count for deaths in this record does not establish that deaths cannot occur, and an observed serious-event count is not a stable comparative risk estimate.

Finally, the registry describes a planned three-year study but lists a terminated status. Without the reason for termination and actual follow-up details, long-term objectives cannot be assumed to have been fully assessed. The record is a useful example of why statistical interpretation depends on design, outcome reporting, analysis methods, and follow-up—not just on the presence of numerical safety entries.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to this record. The study is open-label and single-group, with allocation listed as not applicable. There is no randomized comparator in the registry record, so the posted counts cannot support a controlled estimate of treatment differences. The enrollment of 4 also means the safety entries are based on a very small participant group and should not be treated as precise estimates for a wider population.

The primary endpoint result is not reported in the registry record. This is an important reporting limitation because the endpoint concerns adverse events leading to discontinuation, while the available safety entries concern serious and other adverse-event categories. No analysis results are listed, and no statistical analysis plan is reported. Confidence intervals, p-values, and methods for handling missing data are not reported in the registry record.

The record lists a planned three-year study, a primary completion date of 2023-03-01, and a terminated status. It does not report the reason for termination or the duration of follow-up achieved for participants. As a result, the planned duration cannot be taken as evidence that long-term safety, persistence, or durability objectives were observed over that period. The record also does not specify how many participants contributed data to each listed outcome.

Finally, the adverse-event entries do not provide event-level descriptions sufficient to evaluate timing, severity, attribution, or overlap between categories. The listed serious term and percentage do not resolve these gaps. These limitations restrict interpretation to a narrow description of the registry entries and prevent conclusions about comparative effects or long-term outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open-label Study to Assess the Long-term Safety, Tolerability, Effectiveness, and Durability of Effect of KarXT in Patients With DSM-5 Diagnosis of Schizophrenia — NCT05643170.
• Registry record last updated 2024-06-12; status last verified 2023-07.
• Results first posted 2024-06-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a Phase 3, open-label, single-group study of xanomeline and trospium chloride capsules, identified as KarXT, in participants with schizophrenia. The study was intended to assess long-term safety and tolerability, effectiveness, persistence, and durability of effect. The primary endpoint is the number of participants with treatment-emergent adverse events leading to discontinuation, from first dose to 28 days after last dose, up to approximately 113 days.

Enrollment was 4. The record lists a start date of 2022-11-08, a primary completion date of 2023-03-01, and a terminated status. It reports 1 participant affected in the serious-event category, 3 in the other-event category, and 0 deaths. No numerical primary endpoint result or analyses are reported. The reason for termination and actual follow-up achieved are not reported in the registry record.