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 Safety and Efficacy of Intranasal Epinephrine After Administration of ARS -1 in Subjects With Frequent Urticaria Flares (NCT05496465), a randomized phase 2 study. The primary outcome is Effect of ARS-1 Versus Placebo Based on a Patient Reported Pruritus/Hive Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05496465 |
| Phase | Phase 2 |
| Condition | Urticaria |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | ARS Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People with frequent urticaria flares were the study population. The registry lists urticaria as the condition and records an enrollment of 21. Further eligibility details and a description of the analyzed population are not reported in the registry record.
Intervention
The intervention was intranasal ARS-1, with sequences involving the 1 mg and 2 mg doses. The outcome was intended to capture the effect of ARS-1 on patient-reported itch and hive severity.
Comparator
Placebo was the comparator. The study used a crossover model, with the registry describing sequences that include both ARS-1 doses and placebo. The record does not provide further detail about the timing or conduct of these treatment periods.
Primary question
The primary question was how ARS-1 compared with placebo on a patient-reported pruritus and hive score at 120 (± 10 min) after dosing. The score is described on a scale from 0 (none) to 3 (severe) for itch and hive. Although the registry lists one outcome measure, it posts zero analyses, so it does not report an estimated treatment contrast or its uncertainty.
3. Trial Design
This completed Phase 2 study was randomized, placebo-controlled, and used a crossover model. The registry identifies the study as unmasked, meaning masking is listed as none. Enrollment was 21. The study was sponsored by ARS Pharmaceuticals, Inc.; the registry lists a start date of 2022-07-28 and a primary completion date of 2024-02-29.
The intervention was ARS-1 administered intranasally. The two sequence descriptions include 1 mg ARS-1, 2 mg ARS-1, and placebo in different orders. This crossover structure means the intended comparisons involve treatment conditions experienced within sequences, rather than only separate parallel groups. The registry does not report the details needed to reconstruct the sequence schedule, such as the spacing of doses or any washout procedure.
Random allocation can reduce systematic differences in treatment assignment, while a crossover design can allow within-person comparisons. Those are general design features, not evidence that any particular analysis was performed or that all design assumptions were met. The record does not report how sequence, period, or order effects were handled statistically.
The listed primary outcome is a patient-reported pruritus and hive score assessed at 120 (± 10 min) after dosing. The registry record lists one outcome measure and zero analyses. It therefore describes the planned outcome and timing but does not provide a numerical efficacy estimate, a treatment comparison, or a measure of statistical uncertainty.
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: Cross-over study. All participants received at least one treatment.
Overall Study
| Stage | Sequence 1 | Sequence 2 |
|---|---|---|
| STARTED | 10 | 11 |
| COMPLETED | 8 | 10 |
| NOT COMPLETED | 2 | 1 |
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 | Interventional Treatment |
|---|---|---|
| Participants analysed | 21 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 21 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 17 |
| Sex: Female, Male: Male | Participants | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 21 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 21 |
| Region of Enrollment: United States | participants | 21 |
6. Primary Endpoint
The registry lists the primary outcome as Effect of ARS-1 Versus Placebo Based on a Patient Reported Pruritus/Hive Score, measured over UAS score at 120 (± 10 min) minutes after dosing..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | UAS score 0 to 3 |
| Endpoint classification | Continuous Endpoint |
The primary outcome is described as the effect of ARS-1 versus placebo based on a patient-reported pruritus and hive score. Its stated timeframe is 120 (± 10 min) after dosing. The score description uses a scale from 0 (none) to 3 (severe) for itch and hive. For itch, the descriptions distinguish none, easily tolerated mild itch, bothersome but tolerable moderate itch, and intense itch that is difficult to tolerate. For hives, the listed categories are none, 1-6, 7-12, and >12.
Patient reports can capture symptoms that matter directly to participants and may change over a short period. A specified assessment window also gives a defined time for comparing measurements after dosing. These are general reasons to use symptom scores; the registry does not report validation details or explain how separate itch and hive ratings were combined, if they were combined.
The outcome is identified as a continuous measure analyzed as a mean with standard error as its dispersion description. The record does not post the means, standard errors, or an analysis comparing ARS-1 with placebo. The endpoint description therefore clarifies what was intended to be assessed, but it does not establish the size or direction of any observed difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized crossover trial of intranasal ARS-1 and placebo in people with frequent urticaria flares. Its primary outcome concerns patient-reported pruritus and hive severity at 120 (± 10 min) after dosing. The record lists one outcome measure but zero analyses. It does not post outcome values, a treatment contrast, a confidence interval, or a p-value. As a result, the efficacy question cannot be answered from the posted results.
This distinction matters: an outcome definition is not an outcome finding. The score scale describes how symptom severity could be recorded, while a statistical analysis would need to report the observed measurements and explain how the ARS-1 and placebo conditions were compared. Neither the mean values nor an estimated comparison is reported in the registry record. No direction or magnitude of an effect can therefore be inferred.
The crossover design could support comparisons that account for measurements from the same participant under different conditions. In general, observations from the same person are related, and an analysis should account for that relationship rather than treating them as independent. The registry does not state whether a paired or other crossover analysis was used, nor how periods, sequences, or potential carryover were addressed. This is not evidence that such issues were ignored; their handling is not reported in the registry record.
The outcome is described as a mean with standard error. In general, a mean summarizes the average score, and a standard error describes the precision of an estimated mean. A standard error is not a description of how widely individual scores vary. Because no means or standard errors are posted, the record does not allow assessment of either average symptom level or precision.
The safety record reports zero serious adverse events for each listed condition group and reports other adverse events affecting 6 people in the ARS-1 1mg group, 7 in the ARS-1 2mg group, and 0 in the placebo group; 21 are listed at risk in each group. These figures are descriptive. The registry does not provide enough detail to determine event types, timing, or attribution, and crossover groups should not be added together to infer a count of unique participants.
The posted sample-size calculations are planning illustrations based on an observed effect, not observed power. Without an efficacy estimate posted in the registry record, these calculations should not be treated as a substitute for a reported primary analysis. The study’s own sample-size justification is not reported in the registry record.
9. Statistical Methods Explained
The registry describes a continuous primary outcome summarized as a mean, with standard error as the dispersion measure. It also identifies a randomized crossover design and a patient-reported symptom score. The record does not describe a completed statistical analysis of that outcome. The explanations below describe general statistical concepts and do not claim that any particular method was used in this study.
What does a mean describe?
For a continuous outcome, the mean is the arithmetic average of recorded measurements. It can provide a compact description of the typical score in a group or condition, although it does not show the full distribution of individual scores. A mean difference between conditions can summarize the average contrast, but its meaning depends on the outcome scale and the analysis population. The registry does not post the mean score under either ARS-1 or placebo, or a mean contrast between them.
What does a standard error describe?
A standard error describes the precision of an estimated quantity, such as a mean. It reflects uncertainty in the estimate rather than the spread of individual observations. A confidence interval is a range of values compatible with the data and the statistical model at a stated confidence level. In general, wider intervals indicate less precision, while narrower intervals indicate greater precision. No standard errors or confidence intervals for the primary outcome are reported in the registry record.
Why does crossover structure matter?
In a crossover study, participants receive more than one treatment condition according to an assigned sequence. This can make within-person comparisons useful, because each participant may serve as their own comparison. Such measurements are related rather than independent. An analysis should account for this dependence. It may also need to consider treatment period, sequence, and carryover, depending on the design and available data. The registry lists the crossover model and two sequence descriptions, but the analysis approach and design details needed to assess these issues are not reported in the registry record.
What does randomization contribute?
Randomization assigns treatment sequences by chance and is generally intended to reduce systematic differences in assignment. It does not guarantee that all characteristics will be balanced, especially in a small study, and it does not by itself determine how outcomes should be analyzed. The registry identifies random allocation, but does not report further allocation procedures or a statistical plan.
What can a p-value tell a reader?
In general, a p-value measures how incompatible the observed data are with a specified statistical null model, under the assumptions of the analysis. It is not the probability that a treatment works, nor does it measure the size or clinical importance of a difference. A p-value without an effect estimate and uncertainty interval gives an incomplete account. No p-value for the primary outcome is reported in the registry record.
Why can over-dispersion matter?
Over-dispersion occurs when the variation in observed data is greater than a statistical model expects. In general, failing to account for extra variation can make uncertainty estimates too small and tests too optimistic. The primary outcome is described as a continuous mean score, and the registry does not report a model or data diagnostics. There is no basis to say that over-dispersion was present or that a particular adjustment was needed.
How should planning calculations be read?
The record describes sample-size calculations as planning illustrations based on the observed effect, using 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 calculations are conditional illustrations of the sample size associated with chosen assumptions; they are not observed power and do not demonstrate that the study had a particular probability of detecting an effect. The registry does not report its own sample-size justification. No planning estimate should be interpreted as an efficacy finding.
The record states that the primary outcome has several categories or time points and was not reduced to one comparison. It does not report which comparisons were prespecified, how multiplicity was addressed, or the statistical methods used for the outcome. The absence of an analysis means there are no posted estimates to reinterpret or recalculate.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome measure but zero analyses. It also notes that the primary outcome has several categories or time points and was not reduced to one comparison. The record therefore does not identify a single reported primary contrast, or provide results for comparisons across the score categories or time points.
Multiplicity arises when several hypotheses or comparisons are assessed. In general, testing more comparisons can increase the chance of at least one apparently unusual result under a null model. Statistical plans may address this through a prespecified primary comparison, an adjustment procedure, or a clearly labeled exploratory analysis. The registry does not report whether any such approach was planned or used. The trial's statistical analysis plan is not reported in the registry record.
Missing-data handling is also not reported in the registry record. The record does not say how unavailable symptom scores were handled, whether all enrolled participants contributed outcome data, or what analysis population was used. These details matter because the treatment comparison can depend on which measurements are included and how missing observations are treated.
There is no posted primary outcome estimate from which to assess sensitivity to missing data or multiplicity choices. The registry record also does not report interim analyses or a sample-size justification. These omissions should be read as limits on what can be evaluated from the registry, not as evidence about what investigators did outside the information recorded there.
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 |
|---|---|---|---|
| ARS-1 1mg | 0 | 21 | 0.0% |
| ARS-1 2mg | 0 | 21 | 0.0% |
| Placebo | 0 | 21 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| ARS-1 1mg | 0 of 21 |
| ARS-1 2mg | 0 of 21 |
| Placebo | 0 of 21 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ARS-1 1mg | 6 of 21 |
| ARS-1 2mg | 7 of 21 |
| Placebo | 0 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ARS-1 1mg | ARS-1 2mg | Placebo |
|---|---|---|---|---|
| Nasal discomfort | General disorders | 6 of 21 | 7 of 21 | 0 of 21 |
The adverse-event record lists serious adverse events affecting 0 people for ARS-1 1mg, 0 for ARS-1 2mg, and 0 for placebo. It also lists 0 deaths in each group. No serious adverse-event terms are listed.
For other adverse events, the record reports 6 affected in the ARS-1 1mg group, 7 in the ARS-1 2mg group, and 0 in the placebo group. The number listed at risk is 21 in each group. These are registry counts, not adjusted comparisons. The record does not give event descriptions, severity detail for the other events, timing, or information about whether an event was judged related to treatment.
Because this is a crossover study, the listed groups can reflect treatment conditions experienced within sequences. The group counts should not be summed to infer the number of unique participants, and the registry does not explain how adverse events across periods were attributed or counted. Zero reported serious events means none are listed in these registry fields; it does not establish that the treatments have no safety risks.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed randomized, unmasked, placebo-controlled crossover study evaluated intranasal ARS-1 in people with frequent urticaria flares. It identifies a patient-reported pruritus and hive score at 120 (± 10 min) after dosing as the primary outcome. These design and measurement details clarify what the trial set out to assess.
The record does not establish the size or direction of an effect on symptoms. Although one outcome measure is listed, zero analyses are posted. There are no reported score means, treatment contrasts, confidence intervals, or p-values for the primary outcome. Without those estimates, neither the magnitude nor the precision of the comparison can be evaluated. The outcome scale alone cannot show whether scores differed between ARS-1 and placebo.
The record also does not establish whether any observed symptom difference, if one was measured, would be clinically important. That interpretation would require the results and an appropriate basis for understanding meaningful change, neither of which is reported in the registry record. A statistical comparison, if available elsewhere, would still need to be interpreted alongside the score’s clinical context and the study design.
The safety fields report no serious adverse events or deaths in the listed groups, while other adverse-event counts differ across those groups. These descriptive entries do not establish comparative safety, causality, or the absence of risk. The record lacks event-level detail and does not explain attribution across the crossover periods.
Accordingly, the registry supports a description of the study design, planned symptom measure, and recorded adverse-event counts, but not a conclusion about efficacy or an overall benefit-risk balance. Missing statistical results should not be replaced with assumptions about what the trial found.
13. Why This Trial Matters Statistically
This study raises several statistical issues that are important when reading clinical trial records. First, the crossover design makes the relationship between repeated measurements central. If a participant experiences more than one treatment condition, those measurements are generally not independent. Appropriate analysis should reflect within-person dependence and may need to account for treatment period, sequence, and carryover. The registry does not report how these matters were analyzed.
Second, the outcome is a patient-reported score with descriptions for itch and hive severity. The registry names a mean and standard error, but does not clarify how the symptom components were represented in the analysis or how multiple categories or time points were handled. It explicitly notes that the outcome was not reduced to one comparison. This makes the absence of a reported analysis especially important: the reader cannot identify which contrast, if any, was treated as primary in the results.
Third, statistical interpretation depends on effect estimates and their precision, not only on a study label or a score definition. No efficacy estimate or uncertainty interval is posted. The planning calculations described in the record are illustrations, not observed power and not a substitute for treatment-effect results.
Finally, the registry’s adverse-event counts need careful interpretation in a crossover setting. Counts listed under different treatment conditions do not necessarily represent separate groups of people, and the record does not supply enough detail to compare event risk or attribution. These features make clear reporting of analysis methods and participant-level outcome summaries important for understanding what a trial can show.
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 main limitation for interpreting efficacy is the absence of a posted analysis of the primary outcome. The registry lists one outcome measure and zero analyses. No means, treatment contrasts, standard errors, confidence intervals, or p-values are reported. Consequently, the record does not permit an estimate of treatment effect or its precision.
The primary outcome description includes itch and hive severity categories, and the registry notes that several categories or time points were not reduced to one comparison. The record does not explain how these components were combined or which comparison was intended to carry the primary inference. This limits clarity about the exact estimand, meaning the treatment effect the analysis was designed to estimate.
The crossover model and sequence descriptions are available, but details about treatment periods, spacing, washout, and handling of period or carryover effects are not reported in the registry record. The statistical analysis plan, analysis population, and missing-data methods are also not reported. These gaps prevent assessment of whether the analysis accounted for the design and potential missing outcome measurements.
The safety record provides counts but no descriptions of the other adverse events, their timing, or attribution. In a crossover design, the record does not explain how events were assigned to treatment conditions. The enrollment and group-specific at-risk counts should therefore be read as recorded, not combined into a count of unique participants.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of Intranasal Epinephrine After Administration of ARS -1 in Subjects With Frequent Urticaria Flares — NCT05496465.
- Registry record last updated 2026-04-07; status last verified 2026-03.
- Results first posted 2026-04-07.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry identifies a completed Phase 2 randomized, unmasked, placebo-controlled crossover study of intranasal ARS-1 for frequent urticaria flares. Enrollment was 21. The two sequence descriptions include 1 mg ARS-1, 2 mg ARS-1, and placebo. The primary outcome was a patient-reported pruritus and hive score assessed at 120 (± 10 min) after dosing.
Although one primary outcome measure is listed, the registry reports zero analyses. It therefore provides no numerical efficacy comparison or measure of uncertainty. The adverse-event fields list zero serious events and zero deaths in each group; other adverse events affected 6 in the ARS-1 1mg group, 7 in the ARS-1 2mg group, and 0 in the placebo group. The record does not provide detail sufficient to interpret event types or causality.