Dexmedetomidine in the Treatment of Agitation Associated With Bipolar Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dexmedetomidine in the Treatment of Agitation Associated With Bipolar Disorder (NCT04276883), a randomized phase 3 study. The primary outcome is Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score.

2. Clinical Question

In statistical terms, the central question is whether the measured change in agitation scores differed between either dexmedetomidine dose and placebo at the stated assessment time. The score combines five rated features: poor impulse control, tension, hostility, uncooperativeness, and excitement. Its scale runs from 5, indicating absence of agitation, to 35, indicating extremely severe agitation. A change in this score describes movement on that measurement scale; it is not itself a complete description of every aspect of agitation or the participant’s experience.

The record identifies a secondary outcome assessing PEC total score change over time. It does not report a single primary-outcome comparison or numerical outcome estimates. Consequently, the clinical question can be described from the design and endpoint, but the registry information does not establish the size or precision of any treatment-placebo difference.

3. Trial Design

This was a Phase 3, randomized, quadruple-masked, parallel-group, placebo-controlled study. It evaluated sublingual dexmedetomidine film, BXCL501, for agitation associated with bipolar disorder. The three listed groups received 120 micrograms, 180 micrograms, or placebo film. The registry identifies BioXcel Therapeutics Inc as the sponsor.

The study began on 2020-02-24, reached primary completion on 2020-05-21, and is listed as completed. Registry enrollment is 380. The safety information lists 126 participants at risk in each of the three groups; these safety denominators should not be treated as a complete account of enrollment or as proof that every randomized participant contributed to every outcome analysis. The flow from enrollment through randomization, dosing, and endpoint availability is not reported in the registry record.

Randomization is intended to make assigned groups comparable on average with respect to measured and unmeasured characteristics, while masking is intended to limit influence from knowledge of treatment assignment. The record labels masking as quadruple, but does not specify which roles were masked or describe the procedures used to maintain masking. It also does not report the allocation ratio or the method used to generate and conceal assignments.

Placebo control permits comparison with the same study context without the active study drug. The parallel-group structure means participants were assigned to a group rather than described as crossing between study treatments. Further protocol details, including visit schedules beyond the primary assessment timeframe, are not reported in the registry record. The completed status indicates the study is recorded as finished, but does not by itself indicate what the primary outcome showed.

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: Intent-to-Treat population, defined as all participants in the safety population who have a PEC score post-dose.

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: Safety population (all participants who received study drug)

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score, measured over Baseline and 120 minutes.

The primary endpoint is change from baseline in the Positive and Negative Syndrome Scale-Excited Component total score, with the stated timeframe of baseline and 120 minutes. The PEC comprises five items: poor impulse control, tension, hostility, uncooperativeness, and excitement. Each item is rated from 1, the minimum, to 7, the maximum. The sum ranges from 5, representing absence of agitation, to 35, representing extremely severe agitation.

Because the score covers several features related to agitation, it offers a structured way to quantify symptom severity rather than relying only on an unstructured impression. Assessing change compares each participant’s later score with their baseline score, which can account for where that participant began on the scale. In general, a lower score corresponds to a position closer to the scale’s description of absence of agitation; the registry record does not provide group-level changes to interpret in that direction.

The primary population is defined as the intent-to-treat population, consisting of participants in the safety population who had a PEC score after dosing. This definition describes who was eligible for the stated outcome population, but does not explain how missing baseline or follow-up scores were handled. The registry record does not report numerical endpoint results, variability estimates, or an estimated difference between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a mean of a continuous measure and gives standard deviation as the dispersion measure. The PEC total is a numerical score with a defined range. Describing its mean change is one way to summarize the average movement in score across participants, while the standard deviation conveys how spread out individual scores are around that average. A standard deviation is not the same as the uncertainty around a group mean or a treatment contrast.

What does a treatment contrast add?

A within-group change describes how scores moved among participants assigned to that group. A treatment contrast compares that movement with the movement in another group, such as placebo. The contrast is the quantity that addresses whether the observed average change differs between assigned groups. For interpretation, an estimate should be considered alongside its uncertainty, commonly expressed by a confidence interval. The registry record does not report the primary outcome estimates or confidence intervals, so neither the direction nor the precision of a treatment contrast can be assessed.

How should a confidence interval be read?

In general, a confidence interval is a range calculated from data using a specified method. It conveys uncertainty about an estimated quantity: a narrower interval indicates greater precision under that method, and a wider interval indicates less precision. The interval should be interpreted with the endpoint scale and the comparison in mind. It is not a guarantee that the true effect lies in the interval, and it does not by itself establish clinical importance. No confidence interval for the primary outcome is reported in the registry record.

Why distinguish standard deviation from standard error?

In general, standard deviation describes variation among participant measurements. Standard error describes uncertainty in an estimate, such as a mean, under a particular sampling model. These answer different questions. The primary outcome description gives standard deviation as the dispersion measure, but does not report its value or state which inferential method was used for the treatment comparison. The record therefore does not support reconstructing an estimate of uncertainty from the listed endpoint definition alone.

What role does randomization play?

In general, random allocation helps prevent systematic differences in participant characteristics from determining which group receives which assignment. It supports causal interpretation of an adequately conducted comparison, but does not ensure identical groups in a finite trial or prevent problems from missing outcomes, deviations from assigned treatment, or selective reporting. The registry describes the study as randomized, but does not report the sequence-generation or allocation-concealment procedures. Details needed to evaluate those procedures are not reported in the registry record.

What do masking and the placebo comparison contribute?

Masking can reduce the influence of treatment knowledge on participant experience, outcome assessment, or study conduct. A placebo group provides a concurrent reference for changes that occur in the study context without the active study drug. The record labels the study quadruple-masked and placebo-controlled. It does not identify the masked roles or explain how masking was maintained. These design labels are useful, but the registry information alone cannot establish whether masking was successful.

How do planning calculations differ from observed results?

In general, a sample-size calculation uses assumptions about the effect to detect, variability, significance level, allocation, and statistical method to illustrate a possible study size. The registry’s planning description states a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is set as a stated fraction of the observed effect. These calculations are described as planning illustrations, not as the trial’s design rationale. Their participant counts are not observed results and must not be interpreted as observed power. The registry record does not report its own sample-size justification.

Why does over-dispersion matter in some analyses?

As a general statistical concept, over-dispersion occurs when count data vary more than a model assumes. If present and ignored, estimated uncertainty from that model can be too small, which can make inferential results misleading. The primary endpoint in this study is described as a continuous score analyzed as a mean, not as a count outcome. The registry record does not identify the model or inferential method used for the primary endpoint, so over-dispersion cannot be evaluated as a feature of that analysis.

Interpretation also depends on the exact population and outcome handling. The stated intent-to-treat population includes participants in the safety population who had a PEC score after dosing. This is the definition listed for the primary measure; it does not describe how participants without a post-dose score were treated or whether additional analysis populations were used. Missing-data methods and sensitivity analyses are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and 14 analyses. It describes the primary endpoint at baseline and 120 minutes and a secondary outcome measuring PEC change over time. The primary outcome is not reduced in the registry record to one comparison across its categories or timepoints. The record does not specify which contrasts or analyses were designated as primary for inference, nor does it report a multiplicity adjustment.

In general, multiplicity arises when several outcomes, timepoints, doses, or comparisons are tested. Considering many tests can increase the chance of at least one apparently unusual result even when no underlying difference exists. Statistical plans may address this through a prespecified hierarchy or adjustment, but the approach for this study is not reported in the registry record. The number of listed analyses alone does not establish how they were prioritized or interpreted.

The primary population is defined as participants in the safety population who had a PEC score after dosing. This definition makes a post-dose score part of population eligibility. The registry record does not explain how missing scores were handled, how many participants lacked a required measurement, or whether imputation or sensitivity analyses were performed. Baseline eligibility for the endpoint, handling of early withdrawal, and treatment of deviations from assigned treatment are not reported in the registry record.

Other analysis populations, such as a separately defined per-protocol population, are not reported in the registry record. The record also does not describe whether analyses followed randomized assignment or actual treatment received. These details matter because population definitions and missing-data assumptions can affect both the estimated effect and its uncertainty.

11. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: agitation (0.8%).

The registry lists serious adverse events separately from other adverse events. For serious adverse events, the number at risk was 126 in each group. The listed affected counts were 0 in the 180-microgram group, 1 in the 120-microgram group, and 0 in the placebo group. The record identifies agitation as the top serious term at 0.8%. No deaths were listed in any group.

For other adverse events, the number at risk was also 126 in each group. The listed affected counts were 45 for 180 micrograms, 44 for 120 micrograms, and 19 for placebo. These counts should not be combined with the serious adverse event counts: they refer to a separate category in the registry record. They are descriptive counts, not estimates adjusted for differences between groups.

A count of participants with an event is not necessarily a count of all event occurrences, and the registry record does not provide event-level timing, duration, severity, relatedness assessments, or definitions used for seriousness. The record does not say whether participants could contribute more than one event term. Therefore, the figures describe the reported counts and denominators but do not establish that a treatment caused an event or provide a complete comparison of risk.

The serious-event counts are sparse, so a difference in counts should not be treated as a precise estimate of comparative safety. No confidence intervals or formal statistical comparisons for these safety counts are reported in the registry record.

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

The registry record establishes that a completed Phase 3 randomized, quadruple-masked, placebo-controlled study evaluated two dexmedetomidine doses and placebo for agitation associated with bipolar disorder. It also identifies a structured primary score and its assessment timeframe. These design details explain what the study set out to compare, but do not reveal what the primary outcome comparison found.

The posted registry information does not report numerical primary endpoint results. There is no reported group mean change, treatment-placebo difference, confidence interval, or p-value in the information described. As a result, the size, direction, and precision of a primary treatment effect cannot be determined from this record. Lack of a numerical result in the registry record is not evidence that there was no effect, and it is not evidence that an effect was present.

The safety entries show low serious adverse event counts in the listed groups and differing counts for other adverse events. They do not, by themselves, establish whether treatment caused an event, whether one group had a reliably higher risk, or how these observations should be weighed clinically. The record does not report the detail needed for those judgments.

General statistical interpretation requires more than knowing the design and outcome scale. It depends on estimates, uncertainty, the analysis population, missing-data handling, and the prespecified comparison. The registry does not report several of these details. Even a statistically precise difference would need interpretation in relation to the score’s meaning and the study context; a p-value alone would not describe practical importance.

These findings should therefore be read as a description of the registered study design, outcome definition, and listed safety counts—not as a complete account of efficacy or safety. The registry record does not report enough primary outcome information to support a conclusion about the treatment-placebo comparison.

13. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported treatment contrast are both necessary for statistical interpretation. The PEC total score is specified by its five component items, rating scale, total range, and assessment timeframe. Those details allow a reader to understand what was measured. They do not show how scores changed or how precisely the active groups differed from placebo.

The randomized, masked, parallel-group design is also statistically relevant. Randomization is intended to support fair comparisons, masking can limit some influences of treatment knowledge, and a concurrent placebo group helps distinguish group-specific changes from changes occurring during study participation. Yet these design features cannot substitute for reporting results and their uncertainty. Without endpoint estimates and intervals, readers cannot judge the magnitude or precision of the central comparison.

The record also highlights the importance of transparency about analysis choices. It lists two outcome measures and 14 analyses, but does not identify a single primary comparison across the endpoint’s categories or timepoints, report multiplicity handling, or describe missing-data methods. Such details affect how a result should be interpreted, especially where several possible comparisons may be considered.

Finally, safety counts are most informative when their definitions, denominators, event details, and uncertainty are clear. The recorded counts offer a descriptive snapshot but cannot independently establish causation or comparative risk. Overall, the statistical importance of this trial lies not only in its study design and score definition, but also in the limits imposed when key outcome estimates and analysis details are absent from the registry record.

14. 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 central limitation of the registry information is that it does not report numerical results for the primary PEC endpoint. Group changes, between-group estimates, variability, confidence intervals, and p-values are not reported in the registry record. This prevents assessment of effect direction, magnitude, and precision.

The record lists two outcome measures and 14 analyses, but does not map those analyses to all doses, timepoints, or comparisons. The primary endpoint is described at baseline and 120 minutes, while the secondary measure concerns change over time. A single primary comparison is not identified in the record, and multiplicity handling is not reported.

The intent-to-treat population is defined as participants in the safety population who had a PEC score after dosing. The registry does not report participant flow into that population, the number of missing scores, or methods for handling missing data. The allocation ratio, randomization procedures, allocation concealment, details of the masking roles, and the analysis model are also not reported in the registry record.

The registry enrollment is 380, while the safety groups list 126 participants at risk in each arm. Those entries describe different aspects of the record; no participant-flow explanation is reported. The listed serious and other adverse event counts do not include enough detail to assess timing, severity beyond the serious classification, relatedness, or repeated events. No inferential safety comparisons are reported.

Finally, the sample-size material is described as planning illustration based on the observed effect and stated assumptions, not as the trial’s own design justification. The registry does not report the basis for the original sample-size target. These limitations constrain what can be concluded from the registered information and should not be mistaken for evidence about results that are not reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dexmedetomidine in the Treatment of Agitation Associated With Bipolar Disorder — NCT04276883.
• Registry record last updated 2026-08-11; status last verified 2026-08.
• Results first posted 2023-09-11.
• 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.

18. Record Summary

NCT04276883 is a completed Phase 3 randomized, quadruple-masked, parallel-group, placebo-controlled study sponsored by BioXcel Therapeutics Inc. It evaluated sublingual dexmedetomidine film at 120 micrograms and 180 micrograms against placebo for agitation associated with bipolar disorder. Enrollment is listed as 380.

The primary endpoint was change from baseline in PEC total score at baseline and 120 minutes. The registry defines the intent-to-treat population as participants in the safety population with a post-dose PEC score. Numerical primary outcome results and their uncertainty are not reported in the registry record. Safety entries list serious and other adverse event counts, with no deaths listed. Missing-data procedures, multiplicity handling, and detailed analysis methods are not reported.