This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Treatment of Sunflower Syndrome With ZX008 (Fenfluramine Hydrochloride) in Children and Young Adults (Ages 4-25). (NCT03790137), a na phase 3 study. The primary outcome is % Change in Frequency of Handwaving Episodes.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03790137 |
| Phase | Phase 3 |
| Condition | Photosensitive Epilepsy |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Elizabeth Anne Thiele |
| Results posted | Yes |
2. Clinical Question
Population
Children and young adults ages 4-25 with Sunflower Syndrome were the intended population. The trial record describes 20 participants enrolled and notes that one withdrew 3 days after starting study medication. The primary endpoint description refers to seizure diaries completed by participants or parents, but the analysis population for that endpoint is not reported in the registry record.
Intervention
The study evaluated fenfluramine hydrochloride, also called ZX008 in the trial title. The intervention was administered in an open-label study. Specific dosing and treatment details are not reported in the registry record.
Comparator
There was no separate comparator group. The study used a single-group design, so the primary endpoint compares participants’ reported handwaving-episode frequency during baseline with their frequency during the final month of treatment. This is a within-participant comparison, not a randomized comparison against another treatment or a control group.
Primary question
The primary question was how the frequency of handwaving episodes changed from baseline to Month 3. The endpoint is the median percent change across participants, based on average episodes per day during a one-month baseline and the final month of the three-month treatment period. The actual median and its 95% confidence interval are not reported in the registry record, so the size and precision of the observed change cannot be described.
3. Trial Design
NCT03790137 is a phase 3, open-label, single-group study of fenfluramine hydrochloride in pediatric and adult epilepsy patients ages 4-25 with Sunflower Syndrome. The listed condition is photosensitive epilepsy. The study is marked completed, with enrollment of 20. Its recorded start date is 2019-05-31, and its primary completion date is 2021-11-25. The sponsor is Elizabeth Anne Thiele.
There was no masking and no allocation to different arms. In practical terms, the study was not designed as a blinded comparison between treatment groups. The primary endpoint instead compares a baseline period with a later treatment period for each participant. Such a design can describe change over time among enrolled participants, but without a concurrent control group it cannot separate a treatment-associated change from other explanations, such as natural variation, changes in reporting, or influences related to participation in the study.
The primary endpoint description says participants or parents recorded daily handwaving episodes in seizure diaries during a one-month baseline and during the three-month treatment period. The baseline frequency was calculated as an average of reported daily episodes; this was compared for each patient with the average during the final treatment month. The primary statistic was the median percent change across patients at Month 3.
The record says one participant withdrew 3 days after starting study medication after developing a rash that was not thought to be related to the medication. The participant chose not to challenge the drug at an allergist’s office and withdrew. The status of the remaining participants for the primary endpoint, and the exact analysis population, are not fully reported in the registry record. Details of dosing, adherence, protocol deviations, and the statistical analysis plan 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: After signing consent and enrolling in the study, all patients underwent a baseline echocardiogram, as well as baseline labs. If there were abnormal findings, patients were excluded from participation due to concerns of cardiac toxicity with fenfluramine.
Overall Study
| Stage | Treatment Group |
|---|---|
| STARTED | 20 |
| COMPLETED | 19 |
| NOT COMPLETED | 1 |
Analysis population for the primary outcome, as defined in the registry: One patient withdrew from the study 3 days after starting study medication. This patient developed a rash, which was not thought to be related to study medication. The patient chose not to challenge the drug at an allergists office, and instead withdrew from the study. The other 19 patients completed the core study, but only 17 provided analyzable seizure data.
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.
| Characteristic | Unit | Treatment Group |
|---|---|---|
| Participants analysed | 20 | |
| Age, Continuous | years | 11.9 (7 to 24) |
| Sex: Female, Male: Female | Participants | 15 |
| Sex: Female, Male: Male | Participants | 5 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: United States | participants | 20 |
6. Primary Endpoint
The registry lists the primary outcome as % Change in Frequency of Handwaving Episodes, measured over Month 3.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | % change in hand waving episodes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the median percent change in the frequency of handwaving episodes at Month 3. Episodes were recorded in a seizure diary by the participant or a parent. The record defines an episode as starting when the hand first came up toward the face and ending after a brief pause in waving. Daily counts during the one-month baseline were averaged, as were counts during the final month of treatment. The two averages were compared for each patient, and the median percent change across patients was the primary summary.
This measure was selected to describe change in a recognizable, recurring seizure behavior over time. Diary recording can capture events in everyday settings rather than relying only on a brief clinic observation. The median provides a measure of the middle participant-level change and is less influenced by unusually large values than the arithmetic mean. These are general statistical properties; the registry record does not explain why this endpoint or summary measure was chosen over alternatives.
The convention used to assign the sign of the percent change is not reported in the registry record. More importantly, the posted registry information does not include the median percent change or its 95% confidence interval. Consequently, the magnitude, direction, and precision of the primary endpoint result cannot be assessed from the available record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The design and endpoint are described, but the central numerical result is absent from the registry record. Although the primary outcome is identified as the median percent change in handwaving-episode frequency at Month 3, neither the median estimate nor its 95% confidence interval is reported. There is therefore no posted effect estimate to interpret, and it is not possible to state whether the observed median change was an increase or a decrease, how large it was, or how uncertain it was.
A confidence interval is a range intended to express the statistical uncertainty around an estimate under the assumptions of the analysis. Its width and position help readers judge how compatible the data are with different values of the underlying effect. In this record, the interval is named as the endpoint’s dispersion measure, but its limits are not reported. The precision of the primary result therefore cannot be evaluated.
The single-group design matters when interpreting any change from baseline. A before-and-after comparison can describe how recorded outcomes differed within the observed participants. Without a separate comparator group, however, it cannot establish how much of a change is attributable to the intervention rather than to other influences over time. Open-label diary measurement may also be affected by participants’ or caregivers’ awareness of treatment. These are general considerations for this design, not evidence that any particular bias occurred in this study.
The registry lists secondary outcomes involving EEG spike frequency, photoparoxysmal response, cognitive functioning, quality of life, executive functioning, self-concept, and anxiety. Their outcome names are available, but numerical findings are not included in the registry entries. No conclusions about those outcomes can be drawn from their listing alone.
The record reports 20 enrolled participants and identifies one withdrawal 3 days after treatment began. It does not state how many participants contributed to the primary endpoint analysis or how missing diary observations were handled. Therefore, the relation between enrollment and the endpoint analysis cannot be determined. The adverse-event figures describe safety reporting separately; they do not fill the gap in the primary efficacy estimate.
The appropriate statistical reading is consequently limited: the registry describes a planned within-participant comparison and reports selected safety counts, but it does not provide the primary result needed to quantify the observed change. No claim about the size, direction, or statistical significance of that change is supported by the registry record.
9. Statistical Methods Explained
The primary outcome uses participant-level diary data. For each participant, daily handwaving episodes were recorded during a one-month baseline and a three-month treatment period. The description says the baseline average was compared with the average for the final treatment month. The resulting participant-level changes were then summarized by their median. The endpoint’s timeframe is Month 3.
What does the median describe?
The median is the middle value after observed values are ordered from smallest to largest. It describes the center of the participant-level changes without giving extreme values as much influence as they can have on an arithmetic mean. This can be useful when changes differ substantially between participants or when a small number of observations are unusually large. These are general properties of the median; the registry does not report the distribution of participant-level changes, so it is not possible to tell how the data were shaped in this trial.
A median is not a measure of how similar participants’ outcomes were, and it does not show every participant’s response. A group median can coexist with a wide range of individual results. The registry record does not report participant-level results or a measure of their spread beyond naming a 95% confidence interval for the median percent change.
How should the confidence interval be read?
In general, a confidence interval describes uncertainty around an estimate under a specified statistical procedure. A narrower interval indicates greater precision than a wider interval, while the interval’s location indicates which effect values are compatible with the estimate and method. A confidence interval does not show the range of outcomes for individual participants. The interval limits and the procedure used to calculate it are not reported in the registry record, so neither its precision nor the assumptions behind it can be assessed.
The endpoint is expressed as percent change, but the registry description does not state the exact calculation convention or how the direction of the sign is defined. It gives the source periods and says the averages were compared for each patient, but that description is not enough to reconstruct the calculation. No new calculation should be inferred from the outcome title alone.
What can the design establish?
In a single-group before-and-after design, each participant’s baseline serves as a reference for that participant’s later observation. This can describe change over time among the participants who are measured. It is not the same as a randomized controlled comparison: there is no concurrent group that indicates what would have happened over the same period without the intervention. General alternative explanations for observed change can include natural fluctuation, changes in diary recording, and effects associated with awareness of treatment. These possibilities are design considerations, not findings about this study.
The study was open-label and unmasked. For a diary-based outcome, participants or caregivers knew treatment was being given while recording episodes. General statistical and measurement considerations include the possibility that expectations or recording practices influence reports. The registry does not establish that such an influence occurred, nor does it report procedures intended to assess or reduce it.
What do the analysis details leave unknown?
The registry identifies 13 outcome measures and one analysis, but does not describe a statistical analysis plan, a multiplicity procedure, or the exact analysis population. The primary endpoint description says the median was calculated across all patients, but it does not identify how withdrawals or incomplete diaries were handled. It is not reported whether an intention-to-treat, per-protocol, or other population was used. The number contributing to the primary endpoint should therefore not be assumed from the enrollment count or adverse-event denominator.
There are no reported model details for the primary outcome, no stated method for calculating the confidence interval, and no information about assumptions or diagnostic checks. This outcome is a participant-level change summarized by a median, but the method for handling zeros, incomplete records, or other data features is not reported. These details matter because different analysis choices can affect estimates and uncertainty. Without them, the statistical analysis cannot be reproduced from the registry record.
Sample-size calculations based on an observed effect are planning illustrations rather than observed power. The record’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of the observed effect. This trial itself is single-group, so those two-arm planning assumptions are not a description of its design. The observed primary effect is not reported, and the record does not provide a trial-specific sample-size justification. No conclusion about observed power or the adequacy of enrollment follows from such planning assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures and one analysis. Secondary outcomes include EEG spike frequency, the number of patients with a photoparoxysmal response, cognitive-function measures, quality of life, executive functioning, self-concept, and anxiety. Listing several outcomes raises a general statistical question about multiplicity: when many outcomes or tests are considered, the chance of at least one apparently notable result can increase. Whether and how that issue was addressed in this trial is not reported in the registry record. No adjustment, testing hierarchy, or prespecified distinction between confirmatory and exploratory outcomes is described.
Missing-data handling is also not reported. The primary outcome relies on diary observations across baseline and treatment periods, and the record describes one participant withdrawing 3 days after starting study medication. It does not state whether that participant’s data were included in any analysis, whether other diary records were incomplete, or how missing observations were treated. There is no reported imputation method or sensitivity analysis for missing data.
The record does not identify the analysis population or the number of participants included in the primary endpoint analysis. Enrollment was 20, but it should not be assumed that all enrolled participants contributed usable endpoint data. Nor should the adverse-event population be treated as the efficacy analysis population. Details of protocol deviations and adherence are not reported in the registry record.
Without these details, readers cannot assess whether the analysis population, handling of missing observations, and approach to multiple outcomes were fully prespecified or how sensitive conclusions might be to alternative choices. These are reporting gaps; they do not by themselves demonstrate that the analysis was inappropriate.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Treatment Group | 0 | 19 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Group | 0 of 19 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment Group | 16 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment Group |
|---|---|---|
| Reduced Appetite | General disorders | 8 of 19 |
| Fatigue | General disorders | 7 of 19 |
| Viral Illness | General disorders | 4 of 19 |
| Nocturnal Enuresis | General disorders | 2 of 19 |
| Diarrhea | Gastrointestinal disorders | 2 of 19 |
| Shortness of Breath | General disorders | 2 of 19 |
| Seasonal Allergies | General disorders | 2 of 19 |
| Chest Pain | General disorders | 1 of 19 |
| Rhinorrhea | General disorders | 1 of 19 |
| irritability | General disorders | 1 of 19 |
In the treatment group, the registry reports 19 participants at risk for serious adverse events and 0 participants affected. It reports 19 at risk for other adverse events and 16 affected. Deaths are reported as 0. These are participant counts, not a total count of individual event episodes. The record does not list serious adverse-event terms.
The distinction between serious and other adverse events is important: the 0 serious adverse events does not mean that no adverse events of any kind were reported. The separate other-adverse-event count indicates that 16 of the 19 participants in that safety denominator were affected. The record does not provide the specific other-event types, their severity, timing, or attribution in the registry entries.
The primary endpoint description notes that one participant withdrew 3 days after starting medication after developing a rash. The rash was not thought to be related to study medication, and the participant chose not to challenge the drug at an allergist’s office. This individual account should be read alongside, not substituted for, the aggregate adverse-event counts. Safety counts alone do not establish whether an event was caused by treatment, and the registry information does not provide a comparative safety assessment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 3, open-label, single-group study of fenfluramine hydrochloride in Sunflower Syndrome was completed, with 20 participants enrolled. Its primary endpoint was designed to quantify the median percent change in handwaving-episode frequency from baseline to Month 3 using diary data. However, the median result and its 95% confidence interval are not reported in the registry record. Without those values, the observed magnitude, direction, and precision of the primary outcome cannot be described.
Even if a before-and-after estimate were available, the single-group design would support a description of change among measured participants, not a controlled estimate of what would have happened in the absence of treatment. There was no randomized comparator group, and the study was open-label. General limitations of such designs include potential influences from time, natural variation, reporting behavior, and awareness of treatment. The record does not show whether any of these influenced results.
The outcome is specific to reported handwaving episodes, defined in the record as a period beginning when the hand first came up toward the face and ending after a brief pause in waving. The registry also names EEG, cognitive, quality-of-life, and behavioral outcomes, but their numerical findings are not included in the available information. The presence of an outcome in the record is not evidence of a particular result.
The safety information reports 0 serious adverse events among 19 participants at risk, 16 affected participants for other adverse events among 19 at risk, and 0 deaths. The record also describes one withdrawal after a rash that was not thought to be related to study medication. These figures describe the reported safety data but do not establish causality or provide a comparison with another group.
Accordingly, the available record supports describing the study design, measurement approach, and reported safety counts. It does not support a quantitative conclusion about the primary endpoint or a causal conclusion about treatment effects.
13. Why This Trial Matters Statistically
This trial raises statistical questions that are especially relevant when a rare condition is studied with a single group and a diary-based outcome. The record describes Sunflower Syndrome as a poorly characterized disorder and identifies handwaving episodes as the primary measured outcome. Capturing repeated events in a diary can provide information about behavior outside clinic visits, but the measurement depends on consistent definitions and recording. The record supplies an episode definition and describes who recorded events, while leaving other measurement and data-quality procedures unreported.
The choice to summarize participant-level change with a median is statistically meaningful. A median can be less sensitive than a mean to a few unusually large changes, but it does not show the range of participant experiences. A confidence interval can convey uncertainty around the group estimate, but its value and calculation method are missing from the registry record. These omissions make it impossible to evaluate the result’s precision or distribution from the available information.
The single-group design also illustrates the difference between observing change and estimating a comparative treatment effect. Baseline measurements offer a reference, but they do not provide a concurrent account of change without treatment. Open-label diary measurement adds a general concern about the interpretation of reported outcomes. These are not reasons to assume bias occurred; they explain why design and reporting details are important to statistical interpretation.
Finally, the record identifies multiple outcome measures while leaving multiplicity procedures, missing-data handling, and the analysis population unreported. Those details help readers understand how robust a result may be and what population it represents. In this case, the primary numerical result itself is also absent. The trial is therefore a useful example of why a clear endpoint description and safety counts cannot replace complete reporting of effect estimates, uncertainty, and analysis methods.
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 most consequential limitation for interpreting the registry record is that it does not report the primary endpoint’s median percent change or 95% confidence interval. Without those numbers, the direction, size, and precision of the primary finding are unknown. Numerical results for the named secondary outcomes are also not present in the registry entries.
The study was open-label and single-group, with no comparator arm. A within-participant baseline comparison can describe change over time, but it cannot independently distinguish intervention-related change from other influences. Because the primary outcome was recorded in participant or parent diaries, awareness of treatment is a general measurement consideration. The record does not report validation, adherence checks, or procedures to assess reporting consistency.
The registry reports enrollment of 20 and describes one withdrawal 3 days after starting medication. It does not state the number included in the primary endpoint analysis, how missing diary observations were handled, or which analysis population was used. The endpoint description does not give the calculation convention for percent change, the confidence-interval method, or details of statistical assumptions. Multiplicity handling for the 13 listed outcome measures is not reported.
The safety information gives aggregate counts but does not identify the types of other adverse events or provide a comparative group. A count of affected participants does not establish that events were caused by treatment. Dose details, adherence, protocol deviations, and a trial-specific sample-size justification are not reported in the registry record. These limitations restrict interpretation of both efficacy and safety; they do not establish that the study was conducted improperly.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Treatment of Sunflower Syndrome With ZX008 (Fenfluramine Hydrochloride) in Children and Young Adults (Ages 4-25). — NCT03790137.
- Registry record last updated 2024-11-06; status last verified 2024-10.
- Results first posted 2023-02-08.
- 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.
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18. Record Summary
NCT03790137 is a completed phase 3, open-label, single-group study of fenfluramine hydrochloride in children and young adults ages 4-25 with Sunflower Syndrome. Enrollment was 20. The recorded start date was 2019-05-31, and the primary completion date was 2021-11-25.
The primary endpoint was the median percent change in daily handwaving-episode frequency at Month 3, comparing baseline diary averages with averages during the final treatment month. The median estimate and its 95% confidence interval are not reported in the registry record. The record lists 13 outcome measures and one analysis, but does not describe multiplicity procedures, missing-data handling, or the primary analysis population.
Safety reporting lists 0 serious adverse events among 19 at risk, 16 participants affected by other adverse events among 19 at risk, and 0 deaths. One participant withdrew 3 days after starting study medication following a rash that was not thought to be related. The available information supports description of the design and reported counts, but not a quantitative interpretation of the primary outcome.