Pharmacokinetic Study for IV Allopregnanolone: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic Study for IV Allopregnanolone (NCT04468360), a non-randomized phase 2 study. The primary outcome is Clinician Assessed Sedation Levels for Each Participant.

2. Clinical Question

The scientific context in the registry is the variable response to trauma-focused psychotherapy and the possibility that neurobiological factors may affect the reprocessing of traumatic memories. This pharmacokinetic study is described as preparatory work focused on dosing and safety, rather than as a randomized test of a psychotherapy or a treatment-effect comparison. The registry does not report evidence that would answer whether allopregnanolone changes PTSD symptoms or psychotherapy response.

3. Trial Design

The record identifies this as a Phase 2 study titled “Pharmacokinetic Study for IV Allopregnanolone.” Boston University is listed as the sponsor. The study began on 2022-03-04, had a primary completion date of 2025-04-29, and is listed as terminated. The registry lists enrollment of 11. The record describes PK-1 and PK-2 as small-group pharmacokinetic studies in people with PTSD intended to test dosing and safety before a separate interventional study.

The design is sequential, non-randomized, and unmasked. These features matter for interpretation: participants were not randomly allocated to comparable groups under a randomized design, and no masking is listed. The PK-1 and PK-2 groups received different infusion schedules. PK-1 used a 5-minute loading dose followed by a maintenance infusion over the next 4-5 hours. PK-2 used a 30-minute infusion, then the study drug was discontinued while normal saline continued for the next 4-5 hours. Outcomes were measured during these periods.

Because allocation was non-randomized, differences between group observations cannot automatically be attributed to the dosing schedule. The registry itself says the arms are not a like-for-like control comparison. Sequential conduct also means the registry's design is not a concurrent randomized comparison. The record does not report how enrollment into the groups was ordered, whether any group differences were adjusted for, or what statistical plan was used.

The intervention descriptions identify GMP allopregnanolone with Dexolve in 0.9% saline for infusion, manufactured by the University of California, Davis. The primary outcome is clinician-assessed sedation using the Qualitative Sedation Rating Scale. The record lists 6 outcome measures and 0 analyses. It does not report observed primary outcome counts, an analysis population, or an inferential comparison between the dosing groups. The study's terminated status is a registry status, not by itself an explanation of why the study ended or an indication of the direction of its findings.

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

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 Clinician Assessed Sedation Levels for Each Participant, measured over resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes.

The primary outcome is titled “Clinician Assessed Sedation Levels for Each Participant” and is recorded as a count of participants. Sedation was to be assessed with the Qualitative Sedation Rating Scale at resting pre-infusion and after the loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes. The scale describes five categories: None, Minimal, Moderate, Deep, and Dissociative. Its descriptions distinguish levels by responses to verbal commands or stimulation, cognitive and coordination effects, airway protection, ventilation, and cardiovascular stability.

Tracking sedation during and after an infusion can describe the timing and pattern of observed sedation in a pharmacokinetic study. Repeated assessments may help characterize how participants' recorded sedation categories vary over the planned observation period. These are general reasons for collecting such measurements; the registry record does not state a specific threshold or category that would count as a clinically important result.

The outcome title and unit indicate a participant count, but the registry record does not report the observed counts for the categories at the assessment times. It also does not state how missing assessments, changes between categories, or participant-level summaries were handled. Accordingly, the endpoint description explains what was intended to be assessed, not what was observed. Without the outcome counts and an analysis description, the endpoint cannot support a quantitative comparison of the dosing schedules or an estimate of the precision of any such comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count outcome represent?

The primary endpoint is described as a count of participants with clinician-assessed sedation levels. In general, a count reports how many participants meet a defined category or condition; its interpretation depends on a clear definition of what is counted, the assessment time, and the people included in the denominator. Here, the registry describes a five-category scale and multiple planned assessment times, but does not provide the category counts or say whether the reported endpoint would count participants in each category, use a particular category threshold, or summarize changes across assessment times.

Repeated assessments can reveal whether observations vary over the course of an infusion and subsequent observation. In general, measurements made on the same participant are related rather than independent. An analysis that treats each assessment as unrelated may misrepresent uncertainty. The registry record does not describe any repeated-measures method, participant-level summary, or model, so none should be assumed.

What can a group comparison establish?

Random allocation is a general method for making groups more comparable with respect to both measured and unmeasured factors, on average. This record lists non-randomized allocation and a sequential model, and cautions that the groups are not a like-for-like control comparison. Therefore, a simple contrast between group counts would be descriptive. It would not, by itself, separate the effect of the infusion schedule from differences in participants, timing, or other factors. The registry does not report adjusted analyses or covariates that might address any group differences.

Masking can reduce the influence of expectations on assessment or reporting. The record lists no masking. Because sedation is assessed by a clinician using a rating scale, lack of masking is relevant when considering how assessments were made. This observation does not demonstrate that ratings were biased; it identifies a design feature that could matter. The registry record does not describe assessor training, procedures to standardize ratings, or any steps taken to reduce assessment bias.

How should uncertainty be understood?

In general, an estimate describes the observed data, while a confidence interval describes the range of values reasonably compatible with those data under the model used. A narrow interval indicates greater statistical precision than a wide interval, but neither interval width nor statistical significance alone determines clinical importance. A p value, when used, describes how compatible data are with a specified null model; it does not provide the probability that a hypothesis is true or establish causation.

No primary outcome estimate, confidence interval, or p value is reported in the registry record, and the record lists 0 analyses. Consequently, no inferential conclusion can be drawn from the primary endpoint as recorded. The presence of planned assessment times does not mean that results were analyzed at each time, and no statistical testing procedure can be inferred from the endpoint description.

Why do counts and denominators need to be read together?

A count without its denominator can be difficult to interpret because the number of participants observed may differ across groups or assessment times. A denominator clarifies the number at risk or assessed for the outcome in a defined group. For repeated assessments, the denominator may also change if participants miss visits or stop contributing measurements. The registry gives at-risk counts for its adverse event listing, but it does not give primary endpoint denominators at the planned sedation assessments. The total enrollment does not fill that gap because enrollment alone does not show which participants contributed each specific outcome.

In general, missing outcome data can affect interpretation if missingness is related to the outcome or differs between groups. Appropriate handling depends on why observations are missing and on the analysis target. The registry record does not report missing data, reasons for missingness, imputation, or sensitivity analyses. It is therefore not possible to evaluate whether missing data affected the primary endpoint results.

What does the planning illustration mean?

The registry describes a sample-size planning illustration based on the observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. Such calculations are planning aids: in general, they show the sample size implied by chosen assumptions about the target effect and statistical procedure. They do not show what the study actually detected, and they are not observed power.

The record does not report the observed effect estimate or resulting planning estimates. It also does not report whether these assumptions were part of the original design or whether any sample-size justification was prespecified. The stated planning illustration should not be treated as a description of the study's original rationale or an analysis result. In addition, the equal-allocation assumption in the illustration does not change the record's description of the actual study as non-randomized and sequential.

Why does over-dispersion matter in general?

For count outcomes, a statistical model may assume a particular relationship between the expected count and its variability. Over-dispersion means the observed variability is greater than that assumption allows. If it is ignored, standard errors may be too small and intervals or tests may overstate precision. This is a general consideration for count analyses, not a claim that over-dispersion occurred in this study. The registry record does not describe a count model, dispersion assessment, or any fitted statistical analysis.

Thus, the registry record permits explanation of the planned measure and the general considerations relevant to analyzing it, but it does not document the analysis needed to quantify or test a primary outcome contrast. Any statistical method beyond the stated planning assumptions is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures, with clinician-assessed sedation levels identified as the primary outcome. Multiple outcomes and repeated assessment times can create multiplicity: in general, the more comparisons considered, the greater the chance that at least one result appears noteworthy by chance if each is tested separately. Researchers may address this through a prespecified hierarchy, adjustment, or a clearly exploratory interpretation. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or which comparisons were intended to be confirmatory.

The record lists 0 analyses. It does not report primary endpoint results, analysis methods, confidence intervals, p values, or an analysis population. It also does not report whether all enrolled participants were included in outcome analyses, whether participants were analyzed according to their assigned group, or whether a per-protocol or other population was used. Those details are not reported in the registry record.

Missing data are also not described. The planned sedation assessments occurred at several times, but the record does not give the number assessed at each time, the number with unavailable assessments, reasons for missing observations, or a method for handling missingness. In general, the consequences depend on how and why data are missing, as well as on the analysis used. Without those details, the completeness and potential bias of the primary outcome data cannot be evaluated.

The study's terminated status does not resolve any of these issues. The registry record does not state whether termination affected outcome collection or analysis, nor does it give a reason for termination. Accordingly, multiplicity, missing-data handling, and analysis-population choices remain undocumented in the registry record.

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 5% reporting threshold.

The registry lists serious adverse event counts by group: 0 in the PK-1 Group among 6 at risk and 0 in the PK-2 Group among 5 at risk. It also lists 0 other adverse events in each group and 0 deaths in each group. No serious adverse event terms are listed.

These figures describe the events recorded for the groups and at-risk counts shown. A zero count means that no event of that type was recorded in the listed group for the registry entry; it does not prove that the event cannot occur or establish that there is no risk. Small pharmacokinetic studies can provide limited information about uncommon harms, and the registry record does not provide enough detail to characterize the duration or completeness of adverse event surveillance.

The at-risk counts apply to the adverse event listing and should not be treated as primary endpoint denominators. The registry does not report sedation counts at the scheduled assessment times, nor does it explain whether all participants completed every assessment. The safety figures therefore cannot answer the primary sedation question, and they should not be read as a comparison of treatment safety under randomized conditions. The groups received different dosing schedules in a non-randomized, sequential design, which the registry says is not a like-for-like control comparison.

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

The registry record documents a Phase 2 pharmacokinetic study of intravenous allopregnanolone in people with PTSD. It describes PK-1 and PK-2 dosing schedules, a planned clinician-rated sedation outcome, and the timing of the planned assessments. It also records 0 serious adverse events, 0 other adverse events, and 0 deaths in each of the listed groups. These details describe the study and its recorded safety counts; they do not establish a treatment effect.

The primary outcome counts are not reported in the registry record. There is therefore no basis in this record to say which sedation categories were observed, whether sedation changed over time, or how the groups compared on the primary endpoint. No effect estimate or uncertainty interval is reported. The absence of a reported result is not evidence that there was no effect, and the registry status of terminated does not reveal the reason for termination or what results may exist outside the record.

The design further limits causal interpretation. Allocation was non-randomized, the model was sequential, and the record cautions against treating the arms as like-for-like controls. A group contrast under these conditions could reflect differences in the groups or sequence as well as differences between dosing schedules. The record does not describe an adjustment strategy that would address this concern.

The study is framed as preliminary pharmacokinetic work before a separate interventional study. It does not report a test of psychotherapy, PTSD symptom improvement, or longer-term clinical outcomes. No claim about clinical benefit, lack of benefit, or comparative effectiveness follows from the information recorded. The most supportable conclusion is that the registry describes a planned sedation and safety assessment but does not provide the primary outcome results needed to quantify those findings.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between a planned outcome and a reported result. The registry gives a detailed description of the sedation scale and assessment schedule, but does not provide the resulting participant counts. Without those counts, readers cannot estimate the outcome, its uncertainty, or a contrast between the dosing schedules. A clearly described endpoint is important, but endpoint definition alone does not constitute evidence about the endpoint.

The design also illustrates why allocation matters when interpreting comparisons. A sequential, non-randomized study can support description of observations under different dosing schedules, but the registry cautions that the groups are not a like-for-like control comparison. Randomization is not the only way to learn from clinical research, but without it, group differences require particular care and may be difficult to attribute to the intervention schedule. The record does not report an adjustment method or enough information to evaluate such an approach.

Safety counts require similar restraint. The recorded zero-event counts are useful to describe what appears in the registry, but they do not demonstrate the absence of risk. The at-risk group counts are important context, and the record does not supply further follow-up detail or event definitions that would allow broader conclusions.

Finally, the sample-size planning description should remain distinct from an observed analysis. It states assumptions for an illustration, including a two-sided significance level of 0.05 and a normal approximation, but gives no observed effect estimate or resulting planning values in the record. This reinforces a general statistical distinction: design calculations, measured results, and inferential analyses answer different questions. Here, the registry supports discussion of the design and its limitations, but not a numerical conclusion about the primary endpoint.

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.

A central limitation is that the registry record does not report the primary sedation outcome counts. Although it specifies a rating scale and assessment times, it does not show the observed categories or participant counts at those times. No primary effect estimate, confidence interval, or p value is reported, and the record lists 0 analyses. Statistical precision and the direction or magnitude of any outcome pattern cannot therefore be assessed.

The study was non-randomized, unmasked, and sequential. The registry specifically warns that the groups are not a like-for-like control comparison. These features constrain causal interpretation and may affect clinician-rated outcomes. The record does not explain the allocation sequence, describe assessor procedures, or report adjustment for group differences.

Enrollment is listed as 11, but the record does not provide primary endpoint denominators by assessment time or explain whether assessments were missed. Missing data, withdrawals, deviations, and the analysis population are not reported. This prevents an assessment of outcome completeness and of whether the participants contributing measurements were comparable across groups or times.

The adverse event record lists zero serious events, other events, and deaths in both groups, but does not provide event terms, detailed surveillance procedures, or follow-up information. These counts are not sufficient to rule out uncommon or later events. The registry's terminated status is not accompanied by a reason, so its implications for planned data collection and analysis are unclear.

Finally, although a planning illustration is described, the observed effect and resulting sample-size estimates are not reported. The record also does not explain whether the stated assumptions were used in the original study design. These gaps mean the illustration cannot be used to infer observed power or to judge the study's original sample-size rationale.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetic Study for IV Allopregnanolone — NCT04468360.
• Registry record last updated 2026-06-02; status last verified 2026-05.
• Results first posted 2026-06-02.
• 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

NCT04468360 is a Phase 2, non-randomized, unmasked, sequential pharmacokinetic study sponsored by Boston University and listed as terminated. It concerns intravenous allopregnanolone in people with PTSD and describes PK-1 and PK-2 dosing schedules. Enrollment is listed as 11.

The primary outcome is clinician-assessed sedation using the Qualitative Sedation Rating Scale, with planned assessments from resting pre-infusion through 300 minutes. The registry lists 6 outcome measures and 0 analyses, but does not report the primary sedation counts or statistical results. It lists 0 serious adverse events, 0 other adverse events, and 0 deaths in each group. The registry cautions that the groups are not a like-for-like control comparison. Thus, the record describes the study design and recorded safety counts but does not establish a primary outcome effect or a causal comparison between dosing schedules.