Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of EP262 in Subjects With Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of EP262 in Subjects With Atopic Dermatitis (NCT06144424), a randomized phase 2 study. The primary outcome is Number of Participants With Any Treatment-emergent Adverse Event (TEAE).

2. Clinical Question

The registry record describes a Phase 2a investigation in atopic dermatitis. Its primary outcome concerns safety events after treatment begins, while a listed secondary outcome concerns changes in gene expression signatures and skin histology from baseline to Week 6. That secondary outcome includes epidermal thickness, immune cell infiltration, and markers of epidermal proliferation assessed from lesional-skin biopsies. Results for that secondary outcome are not reported in the registry record.

The central statistical question for the posted primary result is how the observed TEAE frequency in the EP262 arm compares with the frequency in the placebo arm, and how much uncertainty surrounds that contrast. The results are counts in the Safety Analysis Set and an unadjusted comparison. They should be interpreted as the posted safety findings for the participants represented in those groups, rather than as a conclusion about clinical benefit or the experience of people beyond this study.

3. Trial Design

This is a Phase 2a randomized, double-blind, placebo-controlled study with a parallel-group model. The listed intervention is oral EP262, and the listed comparator is placebo. The treatment arms are described as 150 mg EP262 QD and Placebo QD. The registry record names the study EASE and lists Escient Pharmaceuticals, Inc as the sponsor. Enrollment was 32, and the record status is completed.

The recorded start date is 2023-10-25, and the primary completion date is 2024-07-31. The primary outcome is the number of participants with any TEAE up to Week 10. Its analysis population is defined as participants who were randomized and took at least one dose of randomized study drug; safety analyses were based on treatment actually received. The posted arm counts for this endpoint are 21 in the EP262 group and 11 in the placebo group.

The registry also lists a secondary outcome concerning baseline-to-Week 6 changes in gene expression signature and skin histology from lesional-skin biopsies. The record lists six outcome measures but reports a value for the primary TEAE outcome in the information available for this analysis. The registry record does not report posted results for the listed biopsy outcome.

Details such as eligibility criteria, the randomization procedure, the method used to maintain blinding, treatment duration, or the original statistical design assumptions are not reported in the registry record. The study description establishes the broad design and the treatment comparison, but does not justify assumptions about implementation beyond those details.

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: This study was conducted in the United States and Canada.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set: all participants who were randomized and took at least 1 dose of randomized study drug. Safety analyses were based upon treatment actually received.

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 Any Treatment-emergent Adverse Event (TEAE), measured over up to Week 10.

The primary endpoint counts participants who experienced any treatment-emergent adverse event, abbreviated TEAE, up to Week 10. The registry defines an adverse event as an untoward medical occurrence in a participant administered a pharmaceutical product, whether or not it is considered causally related to treatment. This can include an unfavorable or unintended sign, symptom, disease, or clinically significant laboratory finding temporally associated with use of an investigational product.

A TEAE is defined as an adverse event with onset after the first dose of study drug, or an existing event that worsened after the first dose during the study. The measure is a participant count: each participant is classified according to whether any event meeting that definition occurred. It is not a count of every event episode, and the posted primary result does not describe the severity, duration, or cause of each event.

A participant-level event endpoint is used to summarize how many people experienced at least one event during the specified period. Comparing the proportions across treatment groups helps describe the relative frequency of participants with a TEAE in this study. It does not establish that treatment caused an event, because the endpoint definition explicitly does not require a causal relationship.

The Safety Analysis Set includes randomized participants who took at least one dose, with safety analyses based on treatment actually received. The primary endpoint is therefore a safety measure in that analysis population, rather than an efficacy measure of atopic dermatitis improvement.

7. Results Posted in the Registry

• 150 mg EP262 QD: 19.0% (4/21) versus 63.6% (7/11) on control; risk difference -44.6 percentage points (95% CI -77.6 to -11.6), risk ratio 0.30 (0.11–0.80); unadjusted two-proportion z-test p = 0.012.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either had at least one TEAE during the stated period or did not. The registry reports event counts for each group and compares the proportions with an unadjusted risk difference. A risk difference expresses the contrast between group proportions on the same scale as a proportion. For the posted comparison, the negative estimate indicates a lower observed TEAE proportion in the EP262 group than in the placebo group.

Because group sizes differ, counts alone are not enough to understand the comparison. The reported proportions give the event frequency relative to the participants in each group. They should be considered alongside the counts: 4 of 21 in the EP262 group and 7 of 11 in the placebo group. These proportions describe the observed study groups, not a guarantee of the event frequency in another population.

The registry also reports relative measures: a risk ratio and an odds ratio. A risk ratio compares the event proportions directly, while an odds ratio compares event odds. These measures use different scales, so their estimates should not be treated as interchangeable. The registry provides an interval for each estimate. No adjusted estimate is reported.

The unadjusted p-value is 0.012. In general, a p-value assesses how unusual data at least as incompatible with a specified no-difference model would be if that model held and the test assumptions were appropriate. It does not measure the probability that the treatment has no effect, and it does not measure clinical importance. The registry record does not report the test method or a detailed statistical analysis plan, so those details should not be inferred from the p-value alone.

What does an interval estimate convey?

An interval estimate communicates uncertainty around an estimated contrast. A narrower interval indicates greater precision, while a wider interval indicates that a broader range of values remains compatible with the data under the method used. The reported interval for the risk difference extends from -0.776 to -0.116. It is an interval on the risk-difference scale, so its bounds describe possible contrasts on that scale rather than counts of participants.

The registry does not identify the confidence level or interval-construction method in the information reported for this analysis. The limits can therefore be interpreted as the posted uncertainty interval, without assigning a confidence level or assuming a particular calculation procedure. In general, an interval is not a range that contains the true value with certainty; its interpretation depends on the statistical method and assumptions.

Why distinguish participant counts from event counts?

The endpoint is explicitly the number of participants with any TEAE. A participant who experiences multiple events still contributes to the participant-level endpoint according to whether at least one qualifying event occurred. This differs from an event-count analysis, which would count event episodes and could give more weight to participants with repeated events. The posted primary result does not provide total event episodes or an event-rate analysis.

The safety population also matters. The registry defines it as randomized participants who took at least one dose, and says safety analyses were based upon treatment actually received. This is not necessarily the same population or assignment rule that would apply to every possible analysis. The registry does not report a separate intention-to-treat analysis for this endpoint.

What does the result not establish?

The endpoint definition does not require an event to be caused by study drug. The group contrast is therefore a comparison of observed TEAE occurrence, not proof of causation. The posted counts also do not provide detail about event type, seriousness, severity, or timing beyond the overall period up to Week 10. Serious adverse events are reported separately in the safety summary.

The registry identifies a secondary biopsy outcome assessed from lesional skin at Week 6, but no result values for it are reported in the registry record. There are no posted analysis records in the information available for this endpoint beyond the reported comparison. Whether the sponsor conducted other analyses, how missing observations were handled, or whether other outcomes were included in a prespecified testing strategy is not reported in the registry record.

10. Confidence Intervals and Precision

The registry reports a risk difference of -0.446, with an interval from -0.776 to -0.116. This interval expresses uncertainty about the EP262-versus-placebo contrast in the participant proportions with any TEAE. Its width indicates that the estimate is not highly precise: values across a broad range of negative contrasts remain compatible with the reported interval method. The registry record does not state the confidence level or construction method, so no more specific interpretation of coverage can be assigned.

The interval bounds are both below zero. On the risk-difference scale, zero represents no difference between the group proportions; the reported interval therefore does not include zero. The unadjusted p-value is 0.012. The interval and p-value are related summaries of the comparison, but neither describes the probability that the result will repeat in another study, and neither establishes a causal explanation.

Other reported measures give the risk ratio as 0.299, with an interval from 0.111 to 0.804, and the odds ratio as 0.135, with an interval from 0.026 to 0.694. These relative measures also have intervals that span a substantial range. Because the measures use different scales, their numerical estimates should not be compared directly with the risk difference.

The primary safety groups include 21 participants in the EP262 arm and 11 in the placebo arm. With these group sizes, each participant's outcome has a noticeable influence on the observed proportions. The counts are therefore important context for interpreting the interval and the apparent separation between groups. The posted estimate should be treated as uncertain, especially when considering settings beyond the participants and follow-up represented in the registry record.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants across the study and not total events. They are illustrations based on the observed effect, rather than the trial's original enrollment plan. The registry record does not report the original sample-size justification or the assumptions used for the trial's own design.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. For planning for 100% of the observed effect, the figures are 18 participants per arm for 80% power and 24 participants per arm for 90% power. For planning for 75% of the observed effect, the figures are 34 participants per arm for 80% power and 45 participants per arm for 90% power. For planning for 50% of the observed effect, the figures are 78 participants per arm for 80% power and 104 participants per arm for 90% power.

In plain terms, the 80% power column gives the illustrated participants per arm for a study designed to have an 80% chance of detecting the specified effect under the stated assumptions. The 90% power column gives the corresponding planning figure for a higher chance of detection, under those same assumptions. Smaller effects require more participants in these illustrations. This is not observed power: it is prospective planning based on the observed effect and the stated assumptions, not a measure of what the completed trial achieved.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.636; treatment proportion p₁ = 0.190; average p̄ = 0.413.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6964 = 1.3650.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6210 = 0.5226.
4. n = (1.3650 + 0.5226)² / (-0.4459)² = 17.9, rounded up to 18 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.636363636363636                          # control proportion
p1 <- 0.19047619047619                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(6144424)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 18 (80% power), 24 (90% power)
 75% of observed effect: n per arm = 34 (80% power), 45 (90% power)
 50% of observed effect: n per arm = 78 (80% power), 104 (90% power)
power.prop.test: 17.9 
Simulated power at n = 18 per arm: 0.833 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record reports an unadjusted p-value for the primary TEAE comparison and lists a secondary outcome involving gene expression and skin histology. It does not report a multiplicity adjustment or a testing hierarchy across outcomes. When several outcomes or comparisons are examined, multiplicity refers to the increased chance of obtaining at least one apparently notable result by chance. Statistical plans may address this in different ways, but no such plan is reported in the registry record. The unadjusted p-value should therefore be understood as the posted result for this comparison, not as evidence that a correction was applied.

The record does not report how missing data were handled, whether any participants lacked endpoint information, or whether any sensitivity analyses were conducted. The stated Safety Analysis Set includes participants who were randomized and took at least one dose, and safety analyses were based on treatment actually received. The posted arm counts match the counts used for the primary outcome summary, but the information available does not explain the handling of any missing event assessments or other deviations.

The registry does not report a detailed statistical analysis plan, prespecified analysis model, or adjustment for baseline factors. The posted comparison is identified as unadjusted. It is not appropriate to infer whether other analyses were planned or conducted from the absence of reported analysis records. The registry record lists no posted analysis records in the information available.

The primary endpoint's safety population differs conceptually from an analysis that keeps every participant in the originally assigned group regardless of treatment received. The record explicitly says safety analyses were based on treatment actually received, but does not give further details about treatment changes or their handling. The primary outcome should consequently be read according to the population definition stated in the registry, without assuming a different analysis population or missing-data strategy.

14. 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 non-serious adverse event terms

The serious adverse event summary reports zero participants with a serious adverse event in the Placebo QD group and zero in the 150 mg EP262 QD group. It also reports zero deaths in each group. These figures are participant counts within the listed safety groups; they do not imply that all participants experienced no adverse events, because non-serious adverse events are reported separately.

The summary lists 7 participants with other adverse events in the placebo group and 2 in the EP262 group. These are separate safety-summary figures. The primary endpoint reports 7 participants with any TEAE in the placebo group and 4 in the EP262 group. The registry record does not explain the relationship between these categories or why the counts differ, so the other-adverse-event counts should not be substituted for the primary TEAE counts.

Counts of zero serious events are observations from this study, not proof that serious events cannot occur. The registry record does not provide serious-event terms in the listed summary. Interpretation is limited to the reported groups and study record.

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

The primary result describes a lower observed proportion of participants with any TEAE in the EP262 group than in the placebo group during the period up to Week 10. The posted group proportions are 0.191 and 0.636, respectively, and the risk-difference estimate is -0.446, with an interval from -0.776 to -0.116. The comparison is unadjusted, with a p-value of 0.012.

These figures do not establish that EP262 caused the difference. The TEAE definition includes events that do not necessarily have a causal relationship with treatment. The numbers also do not describe event severity, duration, or the total number of event episodes. Serious adverse events and deaths are summarized separately, with zero reported in each group for both categories.

The finding is not an efficacy result. The primary endpoint measures participant-level adverse-event occurrence, not improvement in atopic dermatitis. The registry record lists a secondary Week 6 biopsy outcome concerning gene expression and skin histology, but its results are not reported in the registry record. The safety comparison cannot be used to infer the effect of EP262 on those outcomes.

The estimate also should not be treated as a precise prediction for another population or study. The Safety Analysis Set contains 21 participants in the EP262 group and 11 in the placebo group, and the interval spans a broad range. Other design and analysis details, including the original sample-size rationale and missing-data handling, are not reported in the registry record. The findings are best understood as the posted safety observations and comparison for this completed Phase 2a study.

16. Why This Trial Matters Statistically

This trial illustrates why a statistical interpretation should begin with the endpoint definition. The primary outcome is the number of participants with any TEAE, not the number of event episodes and not a measure of disease improvement. That distinction determines what the counts mean and which conclusions they can support.

It also illustrates the value of presenting both group counts and a contrast with an uncertainty interval. The counts show the observed experience in each group, while the risk difference puts the comparison on an absolute-proportion scale. The risk ratio and odds ratio provide relative scales, but all of these summaries need to be read alongside the group sizes and the uncertainty around the estimates.

The contrast is statistically notable according to the posted unadjusted p-value, but a p-value alone is not a measure of precision or clinical importance. The reported interval provides additional context and remains broad. Together, these summaries show why statistical evidence should not be reduced to a threshold or a single estimate, particularly when the analysis groups are small.

The record also underscores the limits of registry reporting. Some relevant context is available: the safety population definition, treatment groups, endpoint timeframe, and a secondary biopsy outcome. Other details—including the original sample-size assumptions, missing-data methods, multiplicity strategy, and results for the listed secondary outcome—are not reported in the registry record. Distinguishing reported findings from unreported methods is essential when judging how far a result can be interpreted.

17. 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 primary result comes from the safety population, defined as randomized participants who took at least one dose, with analyses based on treatment actually received. The posted counts are 21 for 150 mg EP262 QD and 11 for Placebo QD. The registry record does not report whether participants had missing endpoint data, how such data were handled, or whether sensitivity analyses were performed.

The available record does not give eligibility criteria, baseline characteristics, the randomization procedure, details of blinding implementation, treatment duration, or the original sample-size justification. It also does not report the method used for the primary comparison or the confidence level and construction method for the posted interval. These omissions limit assessment of comparability, precision, and the assumptions underlying the statistical result.

The endpoint concerns any TEAE and does not require a causal relationship to treatment. The primary summary does not provide event types, severity, duration, or total event episodes. The separate adverse-event summary has other-adverse-event counts that differ from the primary TEAE counts for EP262; the registry record does not explain the relationship between these categories.

The unadjusted comparison is reported without a stated multiplicity strategy. The registry lists a secondary Week 6 biopsy outcome but does not report its results. The record also does not report an adjusted primary analysis or other analysis results. These limitations mean the posted comparison should be interpreted as a bounded description of the recorded safety outcome, not as a complete account of all potential study findings.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of EP262 in Subjects With Atopic Dermatitis — NCT06144424.
• Registry record last updated 2025-08-24; status last verified 2025-08.
• Results first posted 2025-08-24.
• 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.

21. Record Summary

NCT06144424 is a completed Phase 2a randomized, double-blind, placebo-controlled, parallel-group study of oral EP262 in atopic dermatitis. The listed treatment groups are 150 mg EP262 QD and Placebo QD. Enrollment was 32; the primary safety analysis includes 21 participants in the EP262 group and 11 in the placebo group.

The primary outcome is the number of participants with any TEAE up to Week 10. The posted counts are 4 with a TEAE in the EP262 group and 7 in the placebo group. The reported risk difference is -0.446, with an interval from -0.776 to -0.116, and the unadjusted p-value is 0.012. The registry also lists a secondary Week 6 biopsy outcome, but its results are not reported in the registry record.