Open-label Safety Trial of PH94B in Social Anxiety Disorder (SAD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-label Safety Trial of PH94B in Social Anxiety Disorder (SAD) (NCT05030350), a na phase 3 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).

2. Clinical Question

This is a safety and tolerability question, not a test of PH94B against placebo or another treatment. Participants were to use the spray when encountering anxiety-provoking situations in daily life. The registry describes safety assessments at monthly visits from baseline, designated Visit 2, to end of treatment, designated Visit 14. Assessments included adverse events, laboratory values, 12-lead ECGs, physical examinations, and vital signs.

The outcome title names both TEAEs and SAEs, while its description identifies participants with at least one SAE. That distinction matters when interpreting the reported counts: the record separately presents participants affected by serious events and an “other” adverse-event count. It does not give a controlled estimate of how many events would have occurred without PH94B, or establish that an event was caused by the spray.

3. Trial Design

This was a phase 3, open-label safety trial of PH94B nasal spray in adults with Social Anxiety Disorder. The record lists a single-group model, no masking, and allocation as not applicable. It reports enrollment of 481. Because the study had no comparator arm, its design cannot provide a randomized, like-for-like estimate of differences between PH94B and another intervention.

The planned regimen was 100 microliter of PH94B 3.2 micrograms to each nostril, up to four times a day as needed for acute anxiety. The stated study purpose was to evaluate safety and tolerability with repeated dosing for up to 12 months. Monthly visits were described from baseline (Visit 2) through end of treatment (Visit 14), with assessments of adverse events, laboratory values, 12-lead ECGs, physical examinations, and vital signs. The record does not establish that every participant received treatment for the full period.

The study start date is 2021-10-01, and the primary completion date is 2022-09-23. Its status is listed as terminated. The reason for termination is not reported in the registry record, so it should not be inferred from the status alone. The record also does not report the actual duration of exposure for each participant, the timing of individual events, or the number of participants who completed follow-up.

These design features define what the results can support. The observed counts describe events recorded among participants in the PH94B group. Without a control group, they do not separate background events from events related to treatment, and open-label conduct means that participants and study personnel were not masked to treatment.

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:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over 12 months.

The primary outcome is titled “Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs),” uses participants as its unit, and has a 12-month timeframe. Its description narrows the measure to subjects with at least one Serious Adverse Event. In other words, the endpoint counts participants who experienced an event, rather than counting every event experienced by each participant.

Counting participants with at least one event is useful in safety reporting because it describes how many people were affected at least once during the observation period. It does not, by itself, show the total number of events, how often events recurred, when they occurred, or how long they lasted. Nor does the count establish that treatment caused an event. Those questions require information beyond a participant count, such as event-level details and an appropriate comparison.

The primary outcome title and description are not fully aligned: the title mentions both TEAEs and SAEs, but the description specifies at least one SAE. The reported results distinguish serious events from other adverse events, but the registry record does not report a fuller endpoint definition, including how treatment emergence was determined. The timeframe is given as 12 months; the study description says dosing could continue for up to that period. The record does not report participant-level follow-up time or clarify how incomplete observation was handled in the endpoint.

In general, safety endpoints help characterize events observed during treatment and guide the interpretation of tolerability data. Their meaning depends on clear event definitions, consistent ascertainment, and context about exposure and follow-up. The participant counts in this record are descriptive; they are not a controlled estimate of treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent? The primary outcome uses participants as its unit and describes subjects with at least one serious adverse event. This is a binary outcome at the participant level: a participant either met the event definition during the observation period or did not. A participant with multiple events would still be counted once for an endpoint defined this way. The registry does not report event-level totals or clarify whether repeat events were analyzed separately.

General statistical explanation: binary outcomes are often summarized by the number of participants meeting a definition and the number assessed. Those figures describe the observed group. A comparison of groups can estimate a difference or ratio in outcome occurrence, subject to the study design and analysis assumptions. Since this trial is single-group, there is no between-group contrast to interpret. The counts alone do not supply a counterfactual estimate of what would have happened in the absence of PH94B.

Why do trial design and analysis matter? The study is described as open-label, with no masking, and has a single-group model. In general, random allocation to a concurrent comparison group helps balance measured and unmeasured characteristics across groups, while masking can reduce some influences on reporting and assessment. Neither feature creates certainty, but their absence is relevant when interpreting descriptive safety data. The record lists allocation as not applicable and does not describe a comparison arm.

The registry lists no analyses. It does not report an inferential statistical plan, a model for the primary endpoint, a confidence interval method, adjustment for covariates, or a strategy for comparing event rates. These methods therefore should not be inferred. In general, an analysis plan defines how outcomes are coded, which participants contribute to each analysis, what estimates are calculated, and how uncertainty is quantified. Without those details, readers cannot assess whether the posted counts reflect a prespecified analysis or a particular treatment of incomplete observations.

What is the role of the planning illustration? The record describes planning illustrations 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; for time-to-event outcomes, the illustration uses total events, and for other outcomes, participants per arm. These are planning assumptions, not the trial’s own design justification. The record’s actual design is single-group and does not have equal allocation between two arms. No sample-size justification is reported in the registry record. A planning illustration is not observed power and should not be read as evidence that the trial had a particular probability of detecting an effect.

General statistical explanation: sample-size planning estimates the amount of information needed to detect a specified effect under chosen assumptions. Its output depends on the effect size, outcome variability or frequency, analysis method, and design. If the assumed effect is based on an observed estimate, planning can be optimistic when that estimate is uncertain. A hypothetical two-arm calculation does not transform a single-group study into a controlled comparison, and it cannot answer whether the study’s observed safety counts are attributable to treatment.

Why might event data require more than simple counts? For safety outcomes, interpretation may depend on the number of participants exposed, duration of exposure, event timing, recurrence, severity, and follow-up completeness. The record gives an at-risk count for the reported categories, but does not provide participant-level time at risk or event timing. In general, exposure-adjusted rates can be useful when observation time differs among participants, but they require suitable exposure-time information. No such rate is reported in the registry record.

General statistical explanation: over-dispersion is relevant when count data vary more than a chosen statistical model expects. It can make uncertainty estimates too small if a model assumes less variability than is present. That concept is not an analysis reported for this trial: the primary endpoint is a participant count, and the registry record lists no model or dispersion estimate. It would be inappropriate to claim that over-dispersion was tested or addressed.

What can uncertainty measures add? A confidence interval can communicate the range of values reasonably compatible with an estimate under a specified method and assumptions. For a single-group count, an interval around an event proportion could describe uncertainty about occurrence in the observed setting, but it would not identify the treatment’s causal effect. The registry record does not report an interval for the counts. A p-value, if calculated, would also depend on a stated hypothesis and method; no such analysis is listed.

The statistical interpretation is consequently limited to descriptive reporting. The record gives event counts, a group at-risk count, a study timeframe, and a design description. It does not report the analytical details needed for a comparative or adjusted conclusion. General methods can explain how such analyses work, but they cannot fill in unreported trial procedures or results.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists no analyses. It does not report whether any outcomes were treated as primary or secondary in a statistical testing hierarchy beyond the primary outcome designation, whether multiple hypotheses were tested, or whether any adjustment for multiplicity was planned. Multiplicity refers generally to the increased chance of misleading findings when many statistical tests or outcomes are considered. It is not possible to determine whether that issue affected this trial’s interpretation without a reported analysis plan and results for the relevant outcomes.

The primary outcome title refers to TEAEs and SAEs, while the outcome description specifically refers to participants with at least one SAE. The posted safety information also separates serious adverse events, other adverse events, and deaths. The record does not explain how these measures relate to one another analytically, whether they were prespecified as separate outcomes, or how overlapping events were handled. These details are not reported in the registry record.

The record does not report a missing-data strategy, an analysis population definition, or the number of participants with complete outcome assessment. It also does not state how withdrawals, incomplete follow-up, or unknown event status were handled. This matters because a participant who is observed for less time may have a different opportunity for an event to be recorded than a participant observed for longer.

General statistical explanation: missing outcome information can affect both the estimated frequency of events and the precision of an estimate. The direction and extent of possible bias depend on why data are missing and how missingness is handled. Those conditions cannot be assessed from the reported counts alone. No imputation, sensitivity analysis, or other missing-data method is reported in the registry record, and none should be assumed.

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: ruptured ectopic pregnancy (0.2%), suicide attempt (0.2%), pelvic abscess (0.2%), ankle fracture (0.2%), diverticulitis intestinal perforated (0.2%).

The PH94B group had 6 participants with at least one serious adverse event among 481 at risk. The record also reports 137 participants with other adverse events among 481 at risk, and 1 death. These figures are participant counts, not a count of every individual event. The record’s serious-event term list gives Ruptured ectopic pregnancy, Suicide attempt, Pelvic abscess, Ankle fracture, Diverticulitis intestinal perforated, and Gallbladder cancer, each accompanied by 0.2%.

The presence of an event during a study does not, by itself, show that treatment caused it. The registry record does not report event attribution, timing, duration, case details, or a comparison group. It also does not clarify how the 1 death relates to the adverse-event categories or whether it was considered treatment-related. No causal conclusion should be drawn from the count alone.

In general, safety counts need context about exposure, follow-up, and event definitions. The intended treatment period was up to 12 months, but the record does not report each participant’s actual time on treatment or time under observation. Thus the counts should be understood as descriptive results reported for this single-group study, not as a controlled estimate of risk or a basis for comparing treatments.

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

The results show that adverse events were recorded among participants in an open-label, single-group PH94B trial. The registry reports 6 participants with at least one serious adverse event and 137 with other adverse events, each among 481 at risk; it also reports 1 death. The serious-event list contains six terms, each accompanied by 0.2%. These registry entries describe the posted safety observations, not a comparison with an untreated or alternative-treatment group.

The results do not establish that PH94B caused any reported event, nor do they establish that the treatment did not cause an event. Without a comparator, the observed counts cannot distinguish treatment-associated events from events that might occur in the study population for other reasons. The open-label design and absence of reported event attribution add further limits to causal interpretation.

The results also do not establish the frequency of events over a common amount of exposure for each participant. The study intended repeated dosing for up to 12 months, but participant-level exposure duration and follow-up completeness are not reported. The record does not report event recurrence, the total number of events, or the timing of each event. The participant counts therefore cannot answer those questions.

The terminated status is a registry status, not an explanation of why the trial ended. The reason for termination is not reported in the registry record. The posted data do not establish whether the trial stopped because of safety findings, operational considerations, or another reason. It would be speculative to assign a cause.

In general, safety evidence is interpreted by considering event definitions, exposure, follow-up, comparison groups, and uncertainty. Here, the available information supports a descriptive account of recorded events in the PH94B group. It does not support a definitive claim about comparative safety, causal attribution, or the likelihood of an event for an individual. Such conclusions would require information and analyses not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates a basic distinction in clinical-trial interpretation: observed events during treatment are not automatically events caused by treatment. A single-group safety study can document what was recorded among participants exposed to an intervention, but it does not provide the concurrent comparison needed to estimate how those observations differ from an alternative. That limitation applies even when the event counts and at-risk group are clearly reported.

The record also illustrates why endpoint wording matters. The primary outcome title refers to TEAEs and SAEs, but its description specifies participants with at least one SAE. Those formulations point to different levels of detail and potentially different event groupings. Readers need the operational definition and analysis approach to know precisely what was counted. The registry record does not report that fuller clarification.

Safety interpretation also depends on time. The study description gives a treatment period of up to 12 months and monthly assessments, but participant-specific exposure and follow-up are not reported. A participant count captures whether an event was recorded, but not how long each participant was observed or how often events occurred. This limits what can be inferred from the counts about event frequency over time.

Finally, the record is a reminder to distinguish a planning calculation from the design and analysis actually used. The stated sample-size assumptions describe a hypothetical two-arm illustration, while the trial is single-group. Such an illustration does not provide observed power or a comparative result. Statistical conclusions depend on the actual design, prespecified methods, and available outcome information—not on a calculation considered separately from them.

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 chief limitation is the absence of a comparator. The study is open-label and single-group, so its safety counts are descriptive and cannot estimate a causal difference between PH94B and another condition. The registry record does not describe randomization or masking, and allocation is listed as not applicable.

Outcome definition is another limitation. The primary outcome title names TEAEs and SAEs, whereas its description specifies participants with at least one SAE. Although the posted adverse-event information separates serious events from other events, the record does not provide a fuller operational definition or explain how the categories relate to the primary outcome.

The registry does not report individual exposure duration, follow-up completeness, event timing, event recurrence, or total event counts. It also does not report a missing-data approach, an analysis population definition, confidence intervals, or an inferential analysis. These omissions restrict evaluation of uncertainty and of how observation time may have affected the reported counts.

The serious-event list supplies terms and percentages but not case narratives, attribution, or outcome details. The record reports 1 death but does not explain its relationship to the listed event categories or whether it was considered treatment-related. No causal conclusion can be drawn from the available description.

The trial is listed as terminated, but the reason is not reported in the registry record. The record also does not report a sample-size justification or a statistical analysis plan. The planning assumptions described are for an illustrative two-arm calculation and do not match the single-group study design. These limitations are specific to interpreting the registered design and results; they do not imply a particular explanation for the trial’s status or findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open-label Safety Trial of PH94B in Social Anxiety Disorder (SAD) — NCT05030350.
• Registry record last updated 2025-10-21; status last verified 2025-10.
• Results first posted 2025-10-21.
• 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.

18. Record Summary

The registry record describes NCT05030350, “Open-label Safety Trial of PH94B in Social Anxiety Disorder (SAD),” as a phase 3, open-label, single-group safety study. It lists enrollment of 481 and a PH94B regimen of 3.2 micrograms, delivered as 100 microliter to each nostril up to four times a day as needed for acute anxiety. The intended treatment period was up to 12 months.

The study start date is 2021-10-01, the primary completion date is 2022-09-23, and the status is terminated. The primary outcome concerns participants with TEAEs and SAEs, although its description specifies at least one SAE. The posted results report 6 participants with serious adverse events, 137 with other adverse events, and 1 death, each event count reported among 481 at risk. No comparator or registered analysis is listed. The reason for termination is not reported in the registry record.