An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy (NCT04794491), a na phase 4 study. The primary outcome is Change in Weekly Rate of Cataplexy Attacks.

2. Clinical Question

This is a study of clinical experience during a treatment transition, not a randomized test of XYWAV against a concurrent control. Its single-group structure can describe outcomes over the stated period in the population analyzed, but cannot by itself separate changes associated with the transition from changes that might have occurred over time for other reasons. The registry identifies narcolepsy as the condition and describes the study rationale as evaluating experience among participants transitioning from Xyrem to XYWAV.

3. Trial Design

The registry describes a Phase 4, multicenter, open-label, single-arm interventional study. Its official title identifies safety, tolerability, effectiveness, and treatment optimization in participants switching from Xyrem to XYWAV for narcolepsy. The listed study status is completed, and the registry enrollment is 62. The recorded study start is 2021-03-22 and primary completion is 2022-11-15.

All participants followed the listed conversion and treatment-optimization arm. The arm description states that participants switched from Xyrem to XYWAV while keeping the dose and regimen of any concomitant anticataplectics or stimulants unchanged throughout the study. The intervention is identified as JZP-258, a drug. The registry lists Jazz Pharmaceuticals as sponsor.

Open-label means the study was not masked, consistent with the registry’s masking entry of none. A single-group design has no concurrent comparison arm, and the allocation entry is not applicable. Accordingly, the primary endpoint is framed as change from baseline to Week 8, rather than a between-group treatment contrast. The study can report observations during the transition, but the design does not create a randomized control comparison.

The registry lists nine outcome measures and no analysis records. That absence of registry analysis entries does not establish that no analyses were conducted; it means numerical analysis details cannot be recovered from the record. In particular, there is no reported primary endpoint estimate, confidence interval, or p-value in the available registry information. The endpoint’s analysis population is described only in part, so its complete operational definition is also not available.

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: The weekly rate of cataplexy attacks was assessed using the XYWAV Efficacy Analysis Set, which included all participants in the XYWAV Safety Analysis Set who finished the course of study. Includes Narcolepsy type 1 participants with a mean weekly rate of cataplexy attack at both the first 7 days of the baseline period and the week 8 visit.

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: Baseline characteristics were assessed using the Safety Analysis Set, which included all participants in the Enrolled Analysis set who received at least 1 dose of Xyrem after providing informed consent.

6. Primary Endpoint

The registry lists the primary outcome as Change in Weekly Rate of Cataplexy Attacks, measured over Baseline to Week 8.

The primary endpoint is change in the mean weekly rate of cataplexy attacks from baseline to Week 8, measured in cataplexy attacks per week. Cataplexy attack frequency is the event being tracked; expressing it as a weekly rate places observations on a common time scale when diary completion may cover differing numbers of days. The registry defines the rate as the total number of attacks reported during a period divided by the number of days in that period for which a diary was completed, multiplied by 7.

The reported summary measure is the mean, with standard deviation as the stated measure of dispersion. In general, a mean describes the average rate in the analyzed population, while a standard deviation describes how spread out individual rates are around that average. A change endpoint uses measurements at the stated time points to describe how the average rate differs over the observation period. It does not, on its own, identify why any change occurred.

The registry says the endpoint was assessed using the XYWAV Efficacy Analysis Set. It describes that set as including participants in the XYWAV Safety Analysis Set who finished the course of study, then begins an additional criterion for participants with Narcolepsy type 1 and diary rates at baseline and another period. The remainder of that criterion is not reported in the registry record. No baseline mean, Week 8 mean, mean change, standard deviation, or interval estimate is reported, so the magnitude and precision of the endpoint cannot be interpreted from the registry information available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. It does not provide a numerical analysis estimate or specify a statistical test for the primary endpoint. The concepts below explain how these methods are generally interpreted; they should not be read as a claim that a particular unreported method was used in this study.

What does a mean change describe?

For a continuous outcome, a mean is an average across the observations in an analysis population. A change from baseline to a later time point summarizes how the outcome differs between those assessments. In this study, the stated quantity is the mean change in weekly cataplexy attack rate from baseline to Week 8. A group mean can be useful for describing the average pattern, but it does not show the full range of participant-level experiences. The standard deviation gives a measure of spread among observations; it is not the same as the uncertainty around the mean.

The registry defines the weekly rate using diary reports: attacks during the period are divided by days with a completed diary, then multiplied by 7. This is a rate-based construction. General statistical point: a rate’s interpretation depends on its numerator and exposure or observation time. Here, diary-completed days form the stated time basis. If diary completion varies, the amount of recorded information can vary too. The registry does not describe any additional adjustment for diary completeness or the handling of missing diary days.

What would uncertainty measures add?

General statistical explanation: a confidence interval gives a range of values compatible with the data and the method’s assumptions. Its width reflects both variability and information available for estimation. A narrower interval generally indicates greater precision under those assumptions; a wider interval indicates more uncertainty. A confidence interval is not a guarantee that the true value lies within its endpoints, and it does not by itself establish importance.

No confidence interval is reported for the primary endpoint in the registry information described. The same is true of a standard error or p-value. Without an estimate and an uncertainty measure, readers cannot judge whether the reported data, if any, would be compatible with a broad range of changes or concentrated around a particular change. No recalculated analysis is appropriate without the underlying summary statistics.

Why does the study structure matter?

The study is single-arm and open-label, with no concurrent control group. The primary endpoint compares baseline with Week 8 within the endpoint definition. In general, a before-and-after comparison can describe change over time in the measured group. It cannot distinguish the effect of the intervention from other factors that may change over the same period. Randomization and a concurrent comparison group can help address some alternative explanations, but they are not features of this design.

Open-label status means the study was not masked. General methodological context: knowledge of treatment can influence participant reporting, investigator assessments, or decisions about continued participation, depending on the outcome and procedures. The primary measure uses diary reports, so recording practices are relevant in principle. The registry record does not report procedures to assess or control any such influence, so no stronger claim about its impact is justified.

How should the planning illustration be understood?

The registry describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such an illustration is a hypothetical planning exercise, not a result observed in this single-arm study and not evidence of the study’s achieved power. The record does not report the illustration’s numerical outputs in the information. It also does not establish that these assumptions were the study’s own design justification.

In general, planning calculations depend on assumptions about the target effect, variability, allocation, significance level, and desired power. Altering an assumed effect changes the amount of information a future study would need. A planning estimate is not a retrospective measure of whether the completed study was adequately powered. Because the record does not provide numerical planning outputs or an actual sample-size justification, no study-specific planning conclusion can be drawn from the description alone.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that observed variability exceeds what a simple count model would predict. A weekly attack rate is derived from counts over diary time, but the registry does not report the distribution of participant-level rates or describe a count model. It would therefore be inappropriate to claim that over-dispersion was present or that a particular model was used. General point: when over-dispersion is present, a model that assumes less variability than the data contain may understate uncertainty. Analysts may use methods that allow greater variability, but the choice depends on the data and analysis plan.

The primary summary is a mean rather than a reported model-based contrast. No information is given about adjustment for baseline values, covariates, repeated measurements, or distributional assumptions. Those details are not reported in the registry record. Statistical explanations of possible methods should not be mistaken for confirmation that any of them were applied.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, but its record contains no analysis entries. It does not report a multiplicity strategy, such as whether one outcome was designated as the sole confirmatory test, whether other outcomes were exploratory, or whether any adjustment was applied across outcomes. The endpoint is identified as primary, but the record does not give enough statistical detail to determine how inferential claims across outcomes were managed.

Multiplicity matters in general when several hypotheses are examined: repeated testing can increase the chance of at least one apparently unusual result under a collection of null hypotheses. Procedures to address this depend on the objectives and analysis plan. No such procedure is reported, so no claim about adjusted or unadjusted significance should be made. There are no reported p-values to interpret.

Missing-data handling is also not reported. The endpoint is calculated from diary-completed days, and the efficacy population description refers to participants who finished the study course, with a further criterion that is incomplete in the registry record. The record does not say how incomplete diaries, missing baseline or Week 8 measurements, withdrawal, or other missing observations were handled. It does not describe an imputation method or a sensitivity analysis. General statistical context: missingness can affect the representativeness of an estimate, especially when the reasons for missing observations relate to the outcome, but the pattern and consequences cannot be judged without relevant information.

The registry distinguishes a safety set from an efficacy set, but the full population rules and participant flow are not available. Consequently, the endpoint denominator and the number contributing measurements at each time point are not reported in the registry record. The reported enrollment and safety counts should not be used to infer an endpoint sample size.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hyperkalaemia (1.7%), fall (1.7%).

The registry reports serious adverse events for an overall group with 60 participants at risk and 2 affected. It reports other adverse events for the same stated number at risk, with 18 affected. These figures describe participants affected in the registry’s safety summary; they are not interchangeable with a count of all event episodes. The record lists 0 deaths.

The serious adverse event terms listed among the most frequent are Hyperkalaemia at 1.7% and Fall at 1.7%. These percentages are reported as written. The registry information does not provide further detail about event timing, severity grading, recurrence, or the relationship of each event to treatment. It also does not establish that events were caused by the treatment transition.

Safety counts are descriptive. They do not, by themselves, provide a controlled estimate of risk because the study had no concurrent comparison group. The registry enrollment is 62, whereas the safety summary reports 60 at risk; the reason for the different figures is not reported in the registry record. These denominators should therefore be read in their stated contexts rather than reconciled by assumption.

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

The registry establishes that the study was a completed, open-label, single-arm evaluation of participants with narcolepsy transitioning from Xyrem to XYWAV. It identifies change in mean weekly cataplexy attack rate from baseline to Week 8 as the primary endpoint and gives the method used to define a weekly rate from diary reports. It also provides a summary of adverse events and describes the endpoint population in part.

It does not report the numerical primary endpoint result. Without the baseline and Week 8 values, mean change, dispersion, or uncertainty, the direction and size of the observed endpoint change cannot be assessed. No statistical test result is reported. This absence should not be interpreted as a null finding or as evidence of no change; it means the registry record does not allow the primary result to be quantified.

Even with a numerical before-and-after estimate, this design would describe change within the study group rather than isolate the effect of the switch from other possible influences. There is no randomized comparator arm. The registry’s account of the endpoint population is incomplete, and missing-data procedures are not reported, which also limits assessment of who contributed data and how incomplete observations affected the result.

The safety summary reports affected participants, the leading serious-event terms with their percentages, and no deaths. These are descriptive observations without a concurrent control for comparison. They do not establish the cause of events or quantify how safety would compare with another treatment strategy.

In general, an outcome estimate, its uncertainty, the analysis population, and the study design all contribute to interpretation. Here, design and endpoint definitions are available, but the primary estimate and several analysis details are not. The defensible reading is therefore limited to what the registry reports about the study structure and safety summary, not a conclusion about the magnitude or precision of effectiveness outcomes.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a transition study whose primary question is framed around within-participant change rather than a randomized group contrast. That distinction determines the scope of inference. A single-arm study can document outcomes during a switch and describe the experience of the analyzed group, but it cannot use a concurrent control to distinguish treatment-related change from other changes over time.

The endpoint definition also illustrates how measurement rules shape a result. The weekly cataplexy rate uses attacks reported during a period and diary-completed days as its time basis. This makes diary completion part of the endpoint’s construction, not merely an administrative detail. The analysis population is defined in part by completion of the study course, while the complete additional eligibility criterion is not reported. Those rules matter when deciding which participants and observations a mean represents.

The record’s reporting gaps are statistically consequential. Without the primary estimate or uncertainty, readers cannot assess magnitude or precision. Without missing-data and multiplicity details, readers cannot evaluate how incomplete observations or multiple outcomes were handled. These omissions do not establish that the underlying analyses were not performed; they limit what can be interpreted from the registry record.

The safety figures show why denominators and outcome definitions must be kept distinct. The overall safety summary uses 60 participants at risk, while registry enrollment is 62, and the endpoint population is separately defined. Each figure belongs to a different stated context. Treating them as the same analysis population would require information not reported in the registry record.

The central statistical lesson is that study design, endpoint construction, analysis population, and transparent reporting jointly determine what a result can support. In this case, the registry supports a description of the intended endpoint and design, but not an assessment of the primary endpoint’s observed size or precision.

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 important limitation for interpreting outcomes is that the numerical primary endpoint result is not reported in the registry record. No mean change, baseline or Week 8 mean, standard deviation, confidence interval, or p-value is available. This prevents assessment of the endpoint’s direction, magnitude, and precision.

The single-arm, open-label design has no concurrent comparator. As a result, within-group change cannot isolate the effect of the treatment transition from other influences over time. The registry does not report additional methods that would address this limitation, and no such methods should be assumed.

The primary analysis population is described only partially. The registry states that the XYWAV Efficacy Analysis Set included participants in the XYWAV Safety Analysis Set who finished the course of study, then gives an incomplete additional criterion involving Narcolepsy type 1 participants and diary rates. The full criterion and the number analyzed are not reported. Missing diary data and other missing outcome handling are also not described.

The registry reports enrollment of 62 and a safety denominator of 60, without explaining the difference. These values refer to distinct stated contexts, but the record does not give participant flow sufficient to reconcile them or establish the primary endpoint denominator. The safety summary is descriptive and does not provide a controlled comparison. Event attribution and further details about timing and recurrence are not reported in the registry record.

Finally, although nine outcome measures are listed, no analysis entries or multiplicity procedures are reported. The sample-size planning description gives assumptions but not numerical outputs, and it does not establish the study’s own design justification. These gaps limit assessment of the analysis strategy as well as the results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy — NCT04794491.
• Registry record last updated 2024-01-09; status last verified 2024-01.
• Results first posted 2024-01-09.
• 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

The registry describes NCT04794491 as a completed Phase 4, multicenter, open-label, single-arm study of participants with narcolepsy switching from Xyrem to XYWAV. The intervention is JZP-258, and the arm description says concomitant anticataplectics or stimulants were to remain unchanged. Registry enrollment is 62; the recorded start and primary completion dates are 2021-03-22 and 2022-11-15.

The primary endpoint is change in mean weekly cataplexy attack rate from baseline to Week 8, calculated using diary-completed days. The registry does not report its numerical result or uncertainty. The overall safety summary reports 2 affected among 60 at risk for serious adverse events, 18 affected among 60 for other adverse events, and 0 deaths. Hyperkalaemia and Fall are each listed at 1.7% among the leading serious-event terms.

The record lists nine outcome measures and no analysis entries. The complete endpoint population criteria, missing-data procedures, and multiplicity approach are not reported in the registry record.