An Open-Label Study of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Study of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001) (NCT05025241), a na phase 2 study. The primary outcome is Safety and Tolerability.

2. Clinical Question

The clinical question is therefore descriptive: what safety and tolerability experience was recorded among participants receiving NNZ-2591 in this study? The study also included pharmacokinetic and efficacy measures, but their results are not included in the registry record in the registry record. The listed secondary outcomes include CGI-I, CIC, CGI-S, Top 3 Concerns, MB-CDI, ORCA, ABC-2, and CSHQ. Their names indicate that multiple measures were planned or recorded, but the outcome values and their interpretation are not reported in the registry record.

3. Trial Design

The registry describes NCT05025241, titled “An Open-Label Study of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001),” as a Phase 2 study. Its official title specifies safety, tolerability, and pharmacokinetics in Phelan-McDermid Syndrome. The study is listed as completed. Its start date is 2022-08-08, and its primary completion date is 2023-11-01.

The design is single-group, open-label, and without masking. Allocation is listed as not applicable. NNZ-2591 was the listed intervention, delivered as an oral solution at 50mg/mL and administered twice daily for 13 weeks. Enrollment was 18. These details describe the registered design; they do not establish how many participants completed treatment or contributed to every outcome.

A single-group design can describe what happened among participants receiving the intervention, including adverse events observed during follow-up. Without a concurrent control group, it cannot directly distinguish events associated with treatment from events that might have occurred in the same population without treatment. Open-label status also means that the registry does not identify masking as a feature of outcome assessment or treatment delivery.

The primary outcome is titled “Safety and Tolerability.” It is expressed as a count of participants, applies to the intention-to-treat population, and has a 13-week timeframe. The description states that the study examined the incidence, severity, and frequency of adverse events, including serious adverse events. The registry also lists 17 outcome measures and 14 analyses, but the analysis methods and detailed results for those measures are not reported in the registry record. The registry does not report a sample-size justification, a detailed statistical analysis plan, or whether any interim analyses were planned or conducted.

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: Following consent, participants underwent 4 weeks of screening for eligibility. If successful, participants were enrolled and commenced open-label active treatment.

Screening

Reasons for not completing this period:

Treatment and Follow Up

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to treat population

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: Intention to treat

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability, measured over 13 weeks.

The primary endpoint is titled “Safety and Tolerability.” Its unit is participants, and its parameter is a count of participants. The stated objective is to examine the incidence, severity, and frequency of adverse events, including serious adverse events, during treatment with NNZ-2591. The timeframe is 13 weeks, and the specified population is the intention-to-treat population.

A participant count is a direct way to describe how many people experienced an event during the defined observation period. It is useful for safety reporting because it keeps the focus on people affected, rather than treating repeated occurrences in one person as if they necessarily represented different participants. The registry separately reports counts for serious adverse events and other adverse events. Those categories should be read as distinct reported summaries; the registry information does not explain whether individuals could contribute to both categories or how repeated events were handled.

Severity and frequency add different information from a participant count. Severity describes how serious an event was, while frequency concerns how often events occurred. The primary outcome description names all three dimensions, but detailed definitions, grading rules, and event-level summaries are not reported in the registry record. The available results therefore support a limited description of participant counts, not a complete assessment of every specified dimension.

In general, safety endpoints are important in a study that evaluates an intervention because they document observed harms and tolerability during the study period. A single-group result is descriptive: it does not provide a controlled estimate of how event risk compares with another treatment or with no treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered design and outcome definition determine what kind of statistical interpretation is appropriate. This study is listed as single-group, open-label, and unmasked, with allocation marked not applicable. The primary outcome is a participant count over 13 weeks. These features support descriptive summaries of observed safety outcomes; they do not create a randomized comparison.

What does a participant count describe?

A count of participants with an event indicates how many people were recorded as having that event under the outcome’s definitions and observation rules. It differs from a count of event episodes: one participant might experience an event more than once, but a participant-level count ordinarily counts that person once for the specified measure. The registry identifies the outcome unit as participants, but detailed rules for repeated events and event categorization are not reported in the registry record.

For this study, the registry reports 1 participant with a serious adverse event, 17 with other adverse events, and 0 deaths. These figures are descriptive counts. They do not, by themselves, provide a comparison with a different group, and they do not establish that an event was caused by the intervention. The study’s single-group design is central to that interpretation.

Why does the design matter?

In a randomized comparison, participants assigned to different groups can provide a basis for estimating a difference between groups, subject to the design and analysis. This study has no randomized comparator, so a treatment contrast is not available from the registered design. Changes in an outcome or the occurrence of events cannot be attributed to NNZ-2591 by comparison with a concurrent control group in this record.

Open-label conduct means masking was absent. In general, knowledge of treatment assignment can affect reporting, observation, or assessment, depending on the outcome and procedures. The registry does not report additional safeguards or assessment procedures that would allow those possibilities to be evaluated. This is not proof that reporting was biased; it is a design feature relevant to interpretation.

How should uncertainty be considered?

In general, a confidence interval expresses a range of values compatible with data and a statistical model, and conveys uncertainty around an estimate. The registry information summarized for this analysis does not include confidence intervals for the adverse-event counts. No interval should therefore be inferred from the counts alone. In general, uncertainty is especially important when the number of participants is limited, because a count from a study group may provide an imprecise estimate of how often an event would occur in a broader population.

Statistical significance and confidence intervals answer different questions, and neither can substitute for a design that supplies a valid comparison for the question of interest. The registry record does not report p-values or a comparative treatment-effect estimate for the primary safety outcome. A significance test is not necessary to describe the observed counts, and a test against an unspecified reference would not establish a controlled treatment effect.

What is known about the analysis plan?

The registry specifies an intention-to-treat population for the primary outcome and reports 17 outcome measures and 14 analyses. It does not report the detailed statistical analysis plan, definitions for analysis populations beyond that primary-population label, rules for missing data, or whether analyses were adjusted for baseline characteristics. It also does not report whether interim analyses were planned or conducted. These details cannot be inferred from the number of outcomes or analyses.

The primary endpoint names incidence, severity, and frequency, but the detailed methods for grading severity and summarizing event frequency are not reported in the registry record. The available participant counts should not be treated as if they answer every component of the endpoint description.

How should planning illustrations be read?

In general, a sample-size calculation uses assumptions about a target effect, significance level, allocation, and statistical model to illustrate how much information might be needed for a planned comparison. The planning illustration associated with this analysis is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect set as a stated fraction of the observed effect. For time-to-event tables, the stated convention is a total number of events; for other tables, it is participants per arm. These are planning assumptions, not features of the registered single-group design and not evidence about actual statistical power in this trial. The illustration’s sample sizes are not reported in the registry record, and no sample-size justification for the trial is reported in the registry record.

In general, over-dispersion occurs when variability in data is greater than a model assumes, which can make standard errors and uncertainty estimates unreliable if not addressed. The primary endpoint is described as a participant count, but the registry does not report a model for the count data or any assessment of over-dispersion. It would be inappropriate to assume a particular model or correction.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures and 14 analyses. It also names several secondary outcomes, including CGI-I, CIC, CGI-S, Top 3 Concerns, MB-CDI, ORCA, ABC-2, and CSHQ. The presence of multiple measures creates the general possibility of multiplicity: when many outcomes or analyses are considered, the chance of observing an apparently notable result by chance can increase. Whether and how that issue was addressed is not reported in the registry record.

The registry does not report a hierarchy of outcomes, a multiplicity adjustment, a prespecified subset for confirmatory testing, or the detailed statistical analysis plan. The number of outcomes and analyses alone does not reveal which analyses were primary, exploratory, or adjusted. Numerical results for the listed secondary outcomes are not reported in the registry record, so their direction, magnitude, and uncertainty cannot be assessed from this information.

The primary outcome population is identified as the intention-to-treat population. That label does not, on its own, explain how missing values were handled or whether every enrolled participant contributed to each safety summary. The registry does not report the extent or pattern of missing data, reasons for missingness, imputation procedures, sensitivity analyses, or analysis-specific participant counts.

These omissions matter because missingness and multiple analyses can affect how confidently results are interpreted. In general, missing-data methods rely on assumptions about why observations are absent, and different assumptions can lead to different conclusions. No such assumptions or methods should be attributed to this study without documentation. The registry record also does not report interim-analysis procedures or stopping rules.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastroenteritis (5.6%).

The registry reports 1 participant at risk for and affected by a serious adverse event, 17 at risk for and affected by other adverse events, and 0 deaths. The listed top serious-event term is gastroenteritis, reported as 5.6%. These are the safety figures available in the registry record for this summary.

They are counts from a single group, not evidence of a difference from a control group. The design was open-label, single-group, and without masking, and no randomized comparator is listed. The counts therefore describe events recorded during the study; they do not establish that NNZ-2591 caused them or that the intervention changed their likelihood.

The primary outcome description refers to incidence, severity, and frequency, but detailed severity grades, event timing, duration, recurrence, and complete event listings are not reported in the registry record. The available information also does not clarify whether a participant could be counted in both serious and other adverse-event categories. The figures should be read as the reported participant summaries, without assuming additional details about event overlap or recurrence.

In general, safety counts are easier to interpret when accompanied by clear event definitions, follow-up completeness, and uncertainty estimates. Those details are not reported in the registry record. The figures are therefore descriptive observations, not precise estimates of risk for other populations or settings.

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

The results mean that the registry records serious and other adverse events among participants in a 13-week, open-label, single-group study of NNZ-2591 in children and adolescents with Phelan-McDermid Syndrome. The reported counts are 1 participant with a serious adverse event, 17 with other adverse events, and 0 deaths. Gastroenteritis is listed among the top serious terms at 5.6%.

These observations are relevant to describing the study’s safety experience. They do not, by themselves, show whether events were caused by the intervention, whether their frequency was higher or lower than it would have been without treatment, or how the results compare with another intervention. The lack of a randomized comparator prevents a direct treatment comparison in this record.

The registry describes the primary outcome in terms of incidence, severity, and frequency. The reported information is narrower than that full description: detailed severity and frequency results are not reported in the registry record. No confidence intervals for the counts, comparative estimates, or primary-outcome p-values are reported in the registry record. The precision of any broader estimate of event occurrence therefore cannot be assessed from these counts alone.

The study also included pharmacokinetic and efficacy measures, and listed secondary outcomes, but their numerical findings are not reported in the registry record. The fact that outcomes were included does not establish what they showed. Nor can the safety results be used as evidence for efficacy.

In general, a trial’s findings apply most directly to the participants, treatment regimen, and follow-up that were studied. The registry identifies a population of children and adolescents with Phelan-McDermid Syndrome and a twice-daily oral regimen over 13 weeks. Further eligibility, adherence, and follow-up details are not reported in the registry record. Readers should not extend the observed counts beyond that context without additional evidence.

13. Why This Trial Matters Statistically

Statistically, this trial matters because it illustrates the distinction between describing events and estimating a comparative treatment effect. Its registered design is single-group and open-label, with no randomized comparator. That design can document how many participants were reported to experience adverse events during the study, but it cannot provide a randomized between-group contrast.

The outcome is framed around participant counts, making the unit of interpretation explicit. The registry reports separate counts for serious adverse events and other adverse events, along with a death count and a serious-event term. Keeping the unit and categories clear helps prevent a participant count from being mistaken for an event-episode count or for a comparison of risks.

The record also illustrates why endpoint definitions and analysis details matter. The primary outcome description includes incidence, severity, and frequency, yet detailed methods and results for all those dimensions are not reported in the registry record. The primary population is named as intention to treat, while missing-data rules and analysis-specific participation are not reported. Those distinctions affect how much can be concluded from a concise count summary.

Finally, multiple outcomes and analyses make it important to know which questions were primary, which were exploratory, and whether any multiplicity approach was planned. Although the registry lists 17 outcome measures and 14 analyses, the detailed statistical plan and multiplicity procedures are not reported in the registry record. The listed counts should therefore be read as descriptive safety observations, with interpretation bounded by the design and the reporting detail available.

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 principal limitation for interpretation is the absence of a randomized comparator. Because the trial is single-group, the reported adverse-event counts cannot show how the same outcomes would have differed under another intervention or without treatment. The open-label design and absence of masking are also relevant when considering event reporting and assessment.

Enrollment was 18, and the at-risk group listed for both serious and other adverse events contains 18 participants. The registry does not explain whether every enrolled participant completed the 13-week treatment period or contributed to every analysis. It also does not report the completeness of follow-up or missing-data handling.

The safety results are limited to participant counts, a death count, and a listed serious-event term. Detailed event definitions, severity grades, event timing, duration, recurrence, and complete event listings are not reported in the registry record. The record does not clarify possible overlap between the serious and other adverse-event categories or provide uncertainty intervals for the counts.

The registry identifies an intention-to-treat population for the primary outcome but does not report detailed analysis methods, an analysis plan, or adjustments for multiple outcomes. It lists 17 outcome measures and 14 analyses, while the detailed methods and numerical results for the secondary outcomes are not reported in the registry record. Sample-size justification and interim-analysis procedures are also not reported in the registry record.

These limitations do not invalidate the reported descriptive counts. They restrict the conclusions those counts can support: they do not provide a controlled causal estimate, a full account of the specified safety dimensions, or a basis for judging the precision of broader population-level event rates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Open-Label Study of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001) — NCT05025241.
• Registry record last updated 2025-06-03; status last verified 2025-06.
• Results first posted 2025-05-30.
• 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

NCT05025241 is a completed Phase 2, open-label, single-group study of oral NNZ-2591 in Phelan-McDermid Syndrome. The listed enrollment is 18. The study began on 2022-08-08, and its primary completion date is 2023-11-01.

NNZ-2591 oral solution at 50mg/mL was administered twice daily for 13 weeks. The primary outcome was safety and tolerability, measured as participant counts in the intention-to-treat population. The registry reports 1 participant with a serious adverse event, 17 with other adverse events, 0 deaths, and gastroenteritis at 5.6% among the top serious terms.

The design has no randomized comparator, and the study was unmasked. Detailed methods for missing data, multiplicity, and the statistical analysis plan are not reported in the registry record. Numerical results for efficacy and the listed secondary outcomes are also not reported in the registry record.