Cannabidiol Oral Solution in Pediatric Participants With Treatment-Resistant Childhood Absence Seizures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cannabidiol Oral Solution in Pediatric Participants With Treatment-Resistant Childhood Absence Seizures (NCT03336242), a non-randomized phase 2 study. The primary outcome is Percent Change From Baseline in Absence Seizure Counts Assessed by Video-electroencephalogram (EEG) at Visit 5.

2. Clinical Question

This is a question about an observed change over time, rather than a randomized comparison of cannabidiol against placebo or another treatment. Without a concurrent control group and a reported primary-outcome estimate, the registry record cannot establish how much change occurred or whether any change was attributable to the intervention. The trial also assessed adverse events and pharmacokinetic measures, but the listed outcomes do not replace the primary seizure-count question.

3. Trial Design

The registry describes NCT03336242 as a Phase 2, open-label, non-randomized, parallel study sponsored by Radius Pharmaceuticals, Inc. It concerns pharmaceutical-grade synthetic cannabidiol oral solution in pediatric participants with treatment-resistant childhood absence seizures. The record lists a planned enrollment of 20 and gives the study status as terminated. The listed start date is 2017-12-29 and the primary completion date is 2019-05-15.

The intervention was organized into three dose cohorts. Cohort 1 received 20 mg/kg/day during the 4-week treatment period. Cohort 2 had a titration period at 20 mg/kg/day for 5 days, followed by 30 mg/kg/day during treatment. Cohort 3 was described as receiving 10 mg/kg/day during treatment, but the primary-outcome description states that no participants were enrolled in that cohort. These are descriptions of the planned dose groups; they do not establish a randomized dose comparison.

The study description includes a 4-week screening period, a titration period of 5 or 10 days depending on cohort, a 4-week treatment period, and a 4-week follow-up period. It also describes tapering for doses >20 mg/kg/day. The primary endpoint was measured at baseline and at Visit 5, specified as Week 4, Day 6 of the treatment period.

Because allocation was non-randomized and masking was absent, participants and study personnel were not described as blinded to treatment assignment. The registry record itself cautions that the arms are not a like-for-like control comparison. It does not report further details of the allocation process, recruitment flow, reasons for termination, or the statistical analysis plan. Those omissions limit assessment of how the design was carried out and how the observed data were selected for analysis.

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: The Sponsor terminated the study and no participants were enrolled in Cohort 3.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Sponsor terminated this study and no participants were enrolled on Cohort 3.

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: All participants who were enrolled and received at least 1 dose of study drug. No participants enrolled in Cohort 3.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline in Absence Seizure Counts Assessed by Video-electroencephalogram (EEG) at Visit 5, measured over Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period).

The primary endpoint was percent change from baseline in absence seizure counts assessed by a 4-hour video-electroencephalogram at Visit 5. Hyperventilation was conducted during the video-EEG to count absence seizures. The registry identifies baseline as Visit 2, Day 1 of the titration period, and Visit 5 as Week 4, Day 6 of the treatment period. The measure therefore compares seizure counts recorded at baseline with counts recorded near the end of treatment.

The record defines percent change as 100 multiplied by the difference between the Week 4 count and baseline count, divided by the baseline count. It defines a negative value as improvement in seizure activity and a positive value as worsening. This direction matters when reading an estimate: values on either side of zero have different stated interpretations. The endpoint is continuous, and the registry describes its summary parameter as a mean with standard deviation.

A video-EEG count offers a standardized, recorded observation of seizure activity during the assessment rather than relying only on a retrospective impression. A change-from-baseline measure also expresses the follow-up count relative to each participant’s own baseline. These features explain the endpoint’s role, but they do not remove measurement variability or design limitations. In particular, the record does not give the primary endpoint’s observed mean, standard deviation, confidence interval, or analysis result. The clinical magnitude and precision of change therefore cannot be judged from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary outcome as a continuous measure summarized by a mean and standard deviation. A mean describes the average value in the analyzed group, while a standard deviation describes how dispersed individual values are around that average. These summaries address different questions: the mean locates the group’s average change, and the standard deviation describes participant-to-participant variability. Neither statistic is reported for the primary endpoint in the registry record, so neither the average change nor its dispersion can be interpreted.

What does percent change represent?

For each participant, the recorded change compares the Week 4 absence seizure count with the baseline count, scaled relative to baseline. Expressing change in this way can make the direction and relative size of change easier to interpret across starting levels. However, a percent-change measure depends on its baseline value. A small baseline count can make the relative change especially sensitive to a change in the follow-up count. The registry record does not describe how zero or otherwise unsuitable baseline counts were handled, so that detail is not reported in the registry record.

The stated sign convention should be kept in view: negative values indicate improvement in seizure activity, while positive values indicate worsening. This is a definition of the measure, not a report that either direction was observed. The primary outcome’s comparison is between baseline and a later assessment within the study; it is not a comparison with an independently randomized control group.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated effect under the assumptions of the analysis. A narrow interval indicates greater statistical precision than a wide interval, but precision is not the same as clinical importance, and an interval does not correct biases caused by study design or missing observations. The registry entries do not report a confidence interval for the primary endpoint. Its width, and whether it includes values corresponding to different interpretations, therefore cannot be assessed.

Why does the design affect interpretation?

Random allocation can help balance known and unknown participant characteristics between comparison groups. This trial is recorded as non-randomized, and its arms are described as dose cohorts rather than a like-for-like control comparison. Open-label conduct also means masking was absent. In general, these design features make it harder to separate an intervention-related change from other differences between participants or changes over time. They do not prove that a result is biased, but they limit how confidently a within-study change can be attributed to treatment.

The parallel structure means the dose cohorts were separate groups, rather than a description of each participant receiving every dose in sequence. The record gives different dose schedules for Cohorts 1 and 2 and states that Cohort 3 had no enrolled participants. Because assignment was not randomized, a simple difference between dose groups would not by itself establish a dose-response relationship. No such primary analysis is reported in the registry record.

How should planning illustrations be read?

General sample-size calculations are planning exercises, not observations from a trial. The registry’s stated assumptions describe an illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is expressed as a fraction of the observed effect. Such calculations depend on the effect estimate used and on the assumptions chosen. They do not show that the trial had a particular probability of detecting an effect, and they are not observed power. No sample-size values or effect fractions are reported in the record details, so no particular planning target can be interpreted.

The record lists 0 analyses. That means the posted information does not include analysis records that would clarify the model, the population analyzed, or the handling of repeated or missing measurements. The registry record does not report adjustment for baseline factors, an approach to outliers, or a method for dealing with skewed values. These methods should not be assumed. General statistical methods can explain what such choices mean, but they cannot fill in details that are not reported for this study.

For safety, the listed figures count participants affected by adverse events within each cohort. They should not be confused with event rates over a known exposure period or with a comparison adjusted for differences between groups. The registry entries do not provide event-specific timing, duration, severity for non-serious events, or exposure-adjusted analyses. The counts are therefore descriptive and do not independently establish comparative safety.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Cohort 1", "Cohort 2")
n   <- c(10, 9)
m   <- c(40.67, 35.12)
sp  <- c(180.919, 121.518)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Cohort 1  10  40.670  180.919  -88.752  170.092
CARM  Cohort 2  9  35.120  121.518  -58.287  128.527

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the primary video-EEG seizure-count endpoint and outcomes concerning adverse events and cannabidiol pharmacokinetics. It records 0 analyses. The registry record does not report a statistical analysis plan, a testing hierarchy, or a method for controlling multiplicity. Without those details, it is not possible to determine how multiple outcomes or possible comparisons were prioritized or interpreted.

Multiplicity matters in general when several outcomes, time points, doses, or statistical comparisons are examined. Considering many results can increase the chance of finding an apparently notable result by chance, so prespecified priorities and appropriate interpretation are useful. This general concern does not establish that any particular result in this trial is misleading; the record does not provide analysis results or procedures to assess.

The registry record also does not report how missing primary-outcome measurements were handled, how many participants contributed to the endpoint analysis, or the definition of the analysis population. The record lists enrollment as 20, while the primary-outcome description states that no participants were enrolled in Cohort 3. These details do not establish who had usable baseline and follow-up video-EEG data. The reason for study termination and any effect of termination on follow-up are not reported in the registry record.

Missing-data methods can affect estimates when participants with observed outcomes differ from those without them. General approaches include describing the extent and pattern of missingness and explaining the assumptions behind any imputation or model-based method. No such approach is reported. In its absence, the completeness and representativeness of the analyzed primary endpoint cannot be assessed, and the listed enrollment should not be treated as proof that every participant contributed to every outcome.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events separately from other adverse events for Cohort 1 and Cohort 2. For serious adverse events, 0 of 10 participants at risk are listed as affected in each cohort. For other adverse events, 6 of 10 in Cohort 1 and 7 of 10 in Cohort 2 are listed as affected. Deaths are listed as 0 in both cohorts. These are descriptive participant counts in the registry, not evidence from a controlled comparison.

A count of participants affected is not the same as a count of event episodes: one participant may have experienced more than one event, and the record does not provide the event-level details needed to characterize that possibility. The listed figures do not identify event types for the non-serious category, their duration, their severity, or whether investigators considered them related to treatment. The registry’s list of top serious-event terms is empty, consistent with no serious events listed as affecting participants in these cohorts, but it does not provide broader event narratives.

The cohorts were non-randomized and there was no like-for-like control group. Differences between the listed counts should therefore not be interpreted as evidence that one dose is safer than another. The record also does not provide exposure-adjusted rates or enough detail to evaluate how follow-up time affected the opportunity to observe events. These figures describe what the registry reports for the listed groups; they do not establish comparative safety or predict outcomes for other patients.

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

The registry record establishes that a Phase 2, open-label, non-randomized study of cannabidiol oral solution was conducted in pediatric participants with treatment-resistant childhood absence seizures and was terminated. It defines the primary endpoint as percent change from baseline in video-EEG absence seizure counts at Visit 5. It also provides cohort dose descriptions and selected adverse-event counts. Those details help readers understand the intended question and the available descriptive information.

The record does not report the numerical primary-endpoint result. There is therefore no basis in the registry information to say how much seizure counts changed, whether the average change was negative or positive, or how precisely it was estimated. The absence of a posted estimate is not a finding of no effect. It is an information gap that prevents quantitative interpretation of the main outcome.

Even if a within-cohort change estimate were available, the design would limit causal interpretation. Participants were not randomized, masking was absent, and the registry cautions that the arms are not like-for-like controls. A change from baseline would describe change among assessed participants, but could not on its own distinguish treatment-associated change from other explanations. The fact that Cohort 3 had no enrolled participants further means its planned dose is not represented by an enrolled cohort in the primary-outcome description.

The safety counts report no participants affected by serious adverse events in either listed cohort, alongside participants affected by other adverse events in both. These are bounded observations from the registry, not proof that serious harms cannot occur or a comparative assessment of risk. The record does not provide the event details needed for a fuller safety interpretation.

Thus the posted information is useful for describing the trial’s structure, endpoint definition, termination status, and reported safety counts. It does not support a conclusion about the magnitude or precision of the primary efficacy outcome, a causal dose comparison, or a definitive assessment of benefit and risk. The reason for termination, missing-data handling, analysis population, and statistical methods are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why a clearly named endpoint is only the beginning of statistical interpretation. The registry defines a video-EEG measure, its assessment times, and the meaning of positive and negative change. Those details specify what an estimate would represent. But without the observed estimate and a measure of its uncertainty, readers cannot determine the size, direction, or precision of the primary result.

It also demonstrates the distinction between a within-group change and a comparative treatment effect. The trial was non-randomized and open-label, and the registry explicitly warns against treating its arms as like-for-like controls. A numerical change in one cohort, if reported, would not automatically answer whether the intervention caused that change. Design and analysis must support the interpretation being made.

Termination and incomplete cohort enrollment add context without explaining the outcome. The record states that no participants were enrolled in Cohort 3, but does not state why the sponsor terminated the study. Statistical readers should separate those reported details from assumptions about why the study stopped or what its results might have shown.

Finally, the safety counts show why denominators and outcome definitions matter. The registry reports participants affected by serious and other adverse events, but those counts do not describe event frequency, time at risk, or a controlled comparison. Reading the figures carefully preserves what they can say while avoiding conclusions they cannot support. The record is therefore a useful case in evaluating what is known, what remains uncertain, and which statistical details are necessary for stronger conclusions.

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 specific to this trial constrain interpretation. The registry record describes a non-randomized, open-label design and explicitly states that the arms are not a like-for-like control comparison. The dose cohorts therefore cannot be treated as randomized alternatives. Cohort 3 was not enrolled, according to the primary-outcome description, so the planned 10 mg/kg/day cohort has no enrolled participants represented there.

The record lists the study as terminated but does not report the reason for termination. It also does not report whether termination affected collection of the primary endpoint or follow-up completeness. Although the record lists enrollment as 20, it does not state how many participants contributed usable baseline and Visit 5 video-EEG measurements. The analyzed population and missing-data approach are not reported in the registry record.

Most importantly, the registry entries do not include the primary endpoint’s observed mean change, standard deviation, confidence interval, or analysis result. The record lists 8 outcome measures and 0 analyses, leaving no posted analysis details with which to assess model choices, multiplicity, or the treatment of individual observations. These omissions prevent evaluation of the magnitude and precision of the primary finding.

The safety information is also limited to participant counts by cohort. Event-level descriptions, timing, duration, and exposure-adjusted summaries are not reported in the record details. The listed counts cannot establish a comparative safety profile, particularly given the non-randomized design and absence of a control group. These limitations mean the registry supports a description of the trial and selected recorded counts, but a broader assessment requires information not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cannabidiol Oral Solution in Pediatric Participants With Treatment-Resistant Childhood Absence Seizures — NCT03336242.
• Registry record last updated 2023-07-21; status last verified 2023-07.
• Results first posted 2023-07-21.
• 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.

19. Record Summary

NCT03336242 is recorded as a terminated Phase 2, open-label, non-randomized, parallel study of cannabidiol oral solution in pediatric participants with treatment-resistant childhood absence seizures. The registry lists enrollment as 20. Its primary endpoint was percent change from baseline in absence seizure counts measured by video-EEG at Visit 5, with negative change defined as improvement and positive change as worsening.

The study described dose cohorts at 20 mg/kg/day, 30 mg/kg/day, and 10 mg/kg/day; the primary-outcome description states that no participants were enrolled in Cohort 3. The registry lists 8 outcome measures and 0 analyses. It does not report the primary endpoint estimate or its precision, the analysis population, missing-data handling, or the reason for termination. Safety entries list no serious adverse events or deaths in Cohort 1 or Cohort 2, with other adverse events reported for participants in both cohorts. Because the study was non-randomized and had no like-for-like control comparison, these entries are descriptive rather than causal or comparative.