Oral Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis in Adult Japanese Participants (ELEVATE UC 40 JAPAN): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oral Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis in Adult Japanese Participants (ELEVATE UC 40 JAPAN) (NCT04706793), a randomized phase 3 study. The primary outcome is Percentage of Participants Achieving Clinical Remission at Week 40 of Study APD334-308.

2. Clinical Question

The primary outcome was clinical remission based on the modified Mayo score. It combined stool frequency, rectal bleeding, and centrally read endoscopic score. The registry reports the remission percentages in the two groups and a risk difference with a 95% confidence interval. Those quantities describe the observed group results and the uncertainty around their contrast; they do not by themselves establish why the groups differed.

This was an extension of Study APD334-302, not a separate study in which the listed treatment assignments began anew. Participants were to continue their same blinded treatment assignment for a total treatment duration of 52 weeks across the two studies: 12 weeks in Study APD334-302 and 40 weeks in Study APD334-308. The question addressed by the posted primary outcome is therefore specifically about remission at Week 40 of the extension among participants included in its analysis, rather than a result for all people with ulcerative colitis.

3. Trial Design

The registry describes a Phase 3, randomized, double-blind, parallel-group, placebo-controlled study. It was a 40-week extension study in Japanese adults with moderately to severely active ulcerative colitis. The brief summary states that the extension followed Study APD334-302 and that participants continued the same blinded treatment assigned in that study. Across both studies, the stated total treatment duration was 52 weeks: 12 weeks in the earlier study and 40 weeks in the extension.

The registry lists 42 participants enrolled. For the primary outcome, 14 participants were analyzed in the placebo group and 28 in the etrasimod 2 mg group. The outcome description defines the Full Analysis Set as all randomized participants who received at least one dose of study intervention, with only those having data available at the specified time points analyzed. The analyzed group sizes therefore describe participants evaluable for this outcome, not necessarily every participant enrolled.

The primary outcome was the percentage achieving clinical remission at Week 40 of Study APD334-308. The registry also lists secondary outcomes relating to endoscopic improvement, symptomatic remission, mucosal healing, remission among participants receiving corticosteroids at entry, and sustained clinical remission. Numerical results are posted for three secondary outcomes; numerical results for the other listed secondary outcomes are not reported in the registry record.

The registry reports the study as completed and gives a start date of 2020-12-25 and a primary completion date of 2022-08-03. Further details of the randomization procedure, allocation ratio planned in the protocol, sample-size justification for the original trial, interim analyses, and the full statistical analysis plan are not reported in the registry record. The observed group sizes should not be treated as evidence of the planned allocation ratio.

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.

Treatment

Reasons for not completing this period:

Follow-up

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set Population (All randomized participants who received at least 1 dose of study intervention). Only those participants with data available at the specified time points were analyzed. "Overall number of participants analyzed" signifies participants evaluable for this outcome measure".

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: Full Analysis Set: All randomized participants who received at least 1 dose of study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving Clinical Remission at Week 40 of Study APD334-308, measured over Week 40 of APD334-308.

The primary endpoint is the percentage of participants achieving clinical remission at Week 40 of Study APD334-308. Remission was defined using the modified Mayo score, a composite of three assessments: stool frequency and rectal bleeding, reported by participants using a daily electronic diary, and endoscopic score, read centrally. The listed remission definition requires a stool-frequency sub-score of 0, or 1 with a decrease of at least 1 point from baseline; a rectal-bleeding sub-score of 0; and an endoscopic score of 1 or less, excluding friability.

Each component sub-score ranges from 0 to 3, and the total modified Mayo score ranges from 0 to 9, with higher scores indicating more severe disease. A composite endpoint can bring several clinically relevant dimensions into one defined outcome. In this case, remission requires the specified conditions across symptoms and endoscopic assessment rather than success on only one component. General statistical context: a binary endpoint such as remission reduces each participant’s measured outcome to whether the stated criteria were met or not met, then summarizes the proportion meeting them in each group.

The endpoint therefore supports a direct comparison of the observed remission percentages. It does not, on its own, convey the degree of change in each score component or the experience of participants who did not meet the full composite definition. Component-level results are not reported in the registry record.

7. Results Posted in the Registry

• Experimental: Etrasimod 2 mg: 25.0% (7/28) versus 7.1% (1/14) on control; risk difference 17.9 percentage points (95% CI -3.1 to 38.8), risk ratio 3.50 (0.48–25.72); unadjusted two-proportion z-test p = 0.165.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants Achieving Endoscopic Improvement at Week 40 of Study APD334-308

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Experimental: Etrasimod 2 mg: 35.7% (10/28) versus 7.1% (1/14) on control; risk difference 28.6 percentage points (95% CI 6.3 to 50.9), risk ratio 5.00 (0.71–35.25); unadjusted two-proportion z-test p = 0.047.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Experimental: Etrasimod 2 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants Achieving Symptomatic Remission at Week 40 of Study APD334-308

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Experimental: Etrasimod 2 mg: 39.3% (11/28) versus 7.1% (1/14) on control; risk difference 32.1 percentage points (95% CI 9.6 to 54.7), risk ratio 5.50 (0.79–38.43); unadjusted two-proportion z-test p = 0.030.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Experimental: Etrasimod 2 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With Mucosal Healing at Week 40 of Study APD334-308

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Experimental: Etrasimod 2 mg: 28.6% (8/28) versus 7.1% (1/14) on control; risk difference 21.4 percentage points (95% CI -0.1 to 42.9), risk ratio 4.00 (0.55–28.90); unadjusted two-proportion z-test p = 0.111.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Experimental: Etrasimod 2 mg and the control. The interval gives the range of effects that remain compatible with the data.

For the three secondary outcomes with numerical results posted, the observed percentages are numerically higher in the etrasimod group than in the placebo group. The corresponding confidence intervals differ in how they relate to zero: some exclude zero while another includes it. This overall pattern is directionally consistent with the primary point estimate, but it does not resolve the uncertainty in the primary result or establish a common effect across distinct outcomes.

The registry lists five secondary outcomes, including outcomes on endoscopic improvement, symptomatic remission, mucosal healing, corticosteroid-related remission, and sustained clinical remission. Numerical results for the latter two listed outcomes are not reported in the registry record. The available secondary findings therefore do not constitute numerical evidence for every listed secondary question.

Secondary analyses commonly involve more than one outcome. General statistical context: when many hypotheses are tested, the chance of observing at least one apparently notable result can increase if each is assessed without adjustment. Whether the sponsor adjusted for multiplicity, used a hierarchy, or treated the secondary outcomes as exploratory is not reported in the registry record. The recalculated secondary p-values are unadjusted and should not be treated as independent confirmation of the primary finding.

These results are best read as supportive descriptive context, not as a substitute for the primary endpoint. Different outcomes capture different aspects of symptoms and endoscopic status, and each has its own uncertainty. Without a reported multiplicity strategy and full analysis plan, the numerical pattern across secondary outcomes should be interpreted cautiously and should not be converted into a broad claim about the treatment’s effects.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants Achieving Endoscopic Improvement at Week 40 of Study APD334-308
• Percentage of Participants Achieving Symptomatic Remission at Week 40 of Study APD334-308
• Percentage of Participants With Mucosal Healing at Week 40 of Study APD334-308
• Percentage of Participants, Who Had Not Been Receiving Corticosteroids for ≥ 12 Weeks, Achieving Clinical Remission at Week 40 of Study APD334-308 Among Participants Receiving Corticosteroids at C5041015 (APD334-302) Study Entry
• Percentage of Participants Achieving Sustained Clinical Remission

9. Statistical Interpretation

10. Statistical Methods Explained

What does the risk difference describe?

The primary contrast is a risk difference: the remission proportion in the etrasimod group minus the remission proportion in the placebo group. In general, a risk difference expresses an absolute contrast between two proportions. It is often easier to interpret in percentage points than as a relative measure because it directly compares the observed proportions. The registry reports the primary difference as 17.86 percentage points. The recalculation uses the posted group summary statistics and is unadjusted; it is not a participant-level model.

The group percentages are 25.0% for etrasimod and 7.1% for placebo. These are observed percentages among participants analyzed for the endpoint. A percentage is not an estimate free of sampling uncertainty: a different set of participants could produce different observed proportions. The confidence interval expresses uncertainty around the group contrast rather than uncertainty around an individual participant’s outcome.

How should the confidence interval be read?

The reported 95% confidence interval for the risk difference is -3.10 to 38.82 percentage points. General statistical explanation: under the method’s assumptions, a confidence-interval procedure is designed to produce intervals that contain the underlying parameter at the stated rate over repeated use. It is not a statement that there is a 95% probability that this particular interval contains the true value. The interval includes zero, the value corresponding to equal proportions, and also includes positive contrasts. Its endpoints show that the data do not pin down a narrow range of plausible differences.

The registry’s analysis-method field for this reported contrast is not populated, so the sponsor’s precise method for constructing the interval is not reported in the registry record. The posted risk difference and interval can still be described as reported, but further claims about the sponsor’s statistical procedure would be speculative.

What does the recalculated p-value add?

The unadjusted recalculated p-value is 0.165. General statistical explanation: a p-value summarizes how compatible the observed data are with a specified null hypothesis under a specified testing procedure. It is not an effect size, a confidence interval, or a direct measure of clinical importance. It should not be read as the probability that the observed result arose by chance, nor as the probability that the null hypothesis is true. The registry does not provide a sponsor-reported p-value for this primary contrast, so the recalculated value should be kept distinct from the sponsor’s posted estimate and interval.

“Unadjusted” indicates that the recalculated value has not been corrected for testing multiple outcomes or contrasts. Whether the sponsor’s planned primary analysis included an adjustment or used a different test is not reported in the registry record. The registry’s reported primary result is a risk difference with a 95% confidence interval, not a stated p-value.

What does the endpoint definition contribute?

The modified Mayo score combines stool frequency, rectal bleeding, and endoscopic score. Its remission definition requires the listed threshold on all three components. This makes the binary outcome an all-criteria measure: a participant who does not meet one required component does not meet the composite remission definition, even if the other components meet their thresholds. General statistical context: composites can capture several dimensions in one endpoint, but the result does not reveal which component most often determined whether a participant met the definition. Component-specific results are not reported in the registry record.

The population description further states that only participants with data available at the specified time points were analyzed. This is an available-data description, not a full account of how missing outcomes were handled. The reasons for missing data, the number missing by group, and any imputation or sensitivity analyses are not reported in the registry record.

Why can over-dispersion matter in other settings?

General statistical explanation: over-dispersion arises when the variability in observed data exceeds what a statistical model assumes. When present and ignored, uncertainty estimates may be too small and tests may appear more decisive than warranted. This primary outcome is a binary percentage, and the registry does not report an over-dispersion estimate or a model-based analysis for it. Over-dispersion should therefore be understood as a general statistical issue, not as a documented feature of this trial’s primary analysis.

How do the planning illustrations work?

The planning illustrations use the observed effect or stated fractions of that effect under assumptions listed with the results: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For each effect scenario, the figures give participants per arm for 80% power and participants per arm for 90% power. General statistical explanation: power is the probability that a specified analysis will detect a defined effect under its assumptions if that effect is present. A smaller effect is harder to distinguish from random variation, so planning for a smaller effect requires more participants. These are planning illustrations, not a description of the original study’s design or analysis plan; the original sample-size justification is not reported in the registry record.

More generally, statistical methods answer different questions: the risk difference describes the observed absolute contrast, the confidence interval communicates uncertainty about that contrast, and the p-value summarizes compatibility with a null model under a testing procedure. None alone settles the interpretation. Their assumptions, the endpoint definition, the analyzed population, and the scope of the registry results all matter.

11. Confidence Intervals and Precision

The primary risk difference is 17.86 percentage points, and its 95% confidence interval ranges from -3.10 to 38.82 percentage points. This interval is wide relative to the observed point estimate and crosses zero. Thus, the posted results are compatible with a modest contrast in the opposite direction, no contrast, or a larger positive contrast. The interval should not be reduced to a simple yes-or-no conclusion: its width conveys that the magnitude is imprecisely estimated.

The group percentages are based on 14 analyzed participants in the placebo group and 28 in the etrasimod group. With group sizes of this scale, a change in the outcome status of a small number of participants can affect the observed percentages. General statistical context: estimates of proportions are often uncertain when the number of observations is limited, and a confidence interval helps show that uncertainty. The interval does not account for every possible limitation, such as missing-data assumptions or limits on generalizing beyond the study population.

The confidence interval is a registry-reported result. The interval’s calculation method is not reported in the registry record. The recalculated unadjusted p-value of 0.165 is another summary, but it does not make the estimate more precise and should not be substituted for the interval. The point estimate identifies the observed direction and size of the contrast; the interval shows how uncertain that estimate remains under its method.

Precision is distinct from clinical importance. The registry record does not specify a threshold for a clinically important difference, so the reported estimate and interval cannot be classified against such a threshold using the posted information. The primary confidence interval supports cautious interpretation of the contrast rather than a precise claim about the underlying difference.

12. 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 events. They illustrate sample sizes under a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set in turn to 100% of the observed effect, 75% of the observed effect, or 50% of the observed effect. These are planning scenarios based on the observed effect, not the original design assumptions for this extension; the trial’s own sample-size justification is not reported in the registry record.

The 80% power column means the planned group size under which the assumed analysis would have an 80% chance of detecting the specified effect, if that effect were present and the planning assumptions held. The 90% power column gives the corresponding group size for a 90% chance. These are target operating characteristics for a hypothetical future design, not probabilities that the result of this completed study is correct. This is not observed power.

Within these planning scenarios, choosing a smaller effect to detect requires more participants per arm. That is expected: a smaller contrast is harder to distinguish from random variation, all else equal. The figures are illustrations rather than a recommendation for a future study, because the appropriate effect, assumptions, design, and analysis would need to be specified for that study. They should not be interpreted as evidence that the current trial was adequately or inadequately sized under its original plan.

13. 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 = 0.071; treatment proportion p₁ = 0.250; average p̄ = 0.161.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5194 = 1.0180.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5038 = 0.4240.
4. n = (1.0180 + 0.4240)² / (0.1786)² = 65.2, rounded up to 66 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 <- 0.0714285714285714                          # control proportion
p1 <- 0.25                          # 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(4706793)
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 = 66 (80% power), 87 (90% power)
 75% of observed effect: n per arm = 104 (80% power), 138 (90% power)
 50% of observed effect: n per arm = 201 (80% power), 269 (90% power)
power.prop.test: 65.2 
Simulated power at n = 66 per arm: 0.827 (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.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary risk difference as 17.86, with a 95% confidence interval from -3.10 to 38.82. The unadjusted recalculation from the posted summary statistics gives the same risk difference and interval. The registry does not flag a discrepancy between the reported and recalculated primary contrast.

The recalculation also gives an unadjusted p-value of 0.165. No p-value is reported for the sponsor’s primary analysis in the registry record, so this p-value should not be attributed to the sponsor. The sponsor’s reported analysis method is not specified in the registry record; the method field for the reported contrast is blank. Agreement of the point estimate and interval does not establish that the sponsor used the same calculation procedure as the unadjusted recalculation.

The sponsor-reported risk difference and interval are the primary posted inferential results. The recalculation is a simple check based on the group summary statistics, not a replacement for a fuller analysis using participant-level data or the sponsor’s complete statistical plan. Further details of any adjustment, covariates, missing-data procedure, or sensitivity analysis are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and multiple secondary outcomes. It does not report a multiplicity-control strategy, such as an adjustment procedure or a prespecified hierarchy for testing the outcomes. The recalculated p-values are unadjusted. Without the analysis plan, it is not possible to determine whether the sponsor planned to control the overall chance of false-positive findings across the set of outcomes, or how the secondary results were intended to support the primary question.

The outcome population is described as the Full Analysis Set: all randomized participants who received at least one dose of study intervention. The registry also states that only participants with data available at the specified time points were analyzed. This gives a basic definition of who contributed to the endpoint analysis, but it does not report the number with missing outcome data, reasons for missingness, or the handling of missing values. Imputation methods, assumptions about missing outcomes, and sensitivity analyses are not reported in the registry record.

These details matter because an available-case analysis can be affected if outcome availability is related to group assignment or the outcome itself. General statistical context: missing-data methods rely on assumptions, and different assumptions can produce different estimates. No particular missingness mechanism or bias should be inferred from the registry description alone.

The registry record also does not report the sponsor’s complete primary analysis model, any covariate adjustment, interim analyses, or the protocol’s original sample-size justification. The posted result remains interpretable as a reported risk difference and interval, but the absence of these details limits the ability to reconstruct the full planned analysis or assess all analytical choices.

16. 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: colitis ulcerative (7.1%), covid-19 (3.6%).

The registry records serious adverse events in 1 of 14 participants in the placebo group and 1 of 28 participants in the etrasimod 2 mg group. Deaths are recorded as 0 in each group. The registry also records other adverse events affecting 8 of 14 participants in the placebo group and 16 of 28 participants in the etrasimod group. These are event counts as posted and should be read separately from the efficacy endpoint.

The listed top serious adverse event terms are colitis ulcerative at 7.1% and COVID-19 at 3.6%. The registry does not provide enough detail in the registry record to assign these terms to specific participants or to establish causation. An adverse event recorded during a study is not, by that fact alone, proof that study treatment caused it. The figures also do not provide a complete account of event timing, duration, severity beyond the serious classification, or treatment relationship.

Small group sizes mean these counts provide limited precision for comparing safety patterns. The posted figures describe what was recorded in this extension; they are not a complete safety assessment or a basis for medical advice.

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

The posted primary data show clinical remission in 25.0% of analyzed participants receiving etrasimod 2 mg and 7.1% receiving placebo at Week 40. The reported risk difference is 17.86 percentage points, with a 95% confidence interval from -3.10 to 38.82 percentage points. The interval includes zero, and the recalculated unadjusted p-value is 0.165. Together, these results describe a higher observed proportion in the etrasimod group but leave substantial uncertainty about the underlying contrast.

These statistics do not establish that etrasimod works or does not work. They do not show the probability that a participant will achieve remission in another setting, nor do they determine whether the observed difference is clinically important. The registry record does not state a threshold for a clinically important difference. The confidence interval concerns the estimated group difference under its method; it does not capture every uncertainty related to study design, missing data, or generalizability.

The result applies to the participants analyzed in this Japanese extension study at its specified Week 40 time point. Participants continued their blinded treatment assignment from Study APD334-302, and the endpoint population included randomized participants who received at least one dose and had available data at the time point. The findings should not automatically be extended to other populations, treatment durations, or clinical settings.

The secondary outcomes offer additional but limited context. Their posted numerical results are not a replacement for the primary endpoint, and the registry does not report whether multiplicity was addressed. Safety counts are also descriptive and cannot, by themselves, establish whether an event was caused by treatment. The registry statistics support a careful account of observed results and their uncertainty, not individual treatment decisions.

18. Why This Trial Matters Statistically

This study illustrates why a clinical result should be read through both its point estimate and its uncertainty. The observed primary risk difference is positive, but its 95% confidence interval extends across zero and spans a broad range. Considering only the point estimate would omit important information about precision; considering only a significance threshold would omit the size and uncertainty of the observed contrast.

The trial also demonstrates the distinction between a sponsor-reported analysis and a simple unadjusted recalculation. Here, the reported primary risk difference and confidence interval agree with the recalculation, while the recalculated p-value is not a sponsor-reported p-value. Those quantities have different provenance and should not be conflated. The registry’s lack of a detailed analysis method or multiplicity plan also shows why a result may be numerically clear but analytically incomplete.

Finally, the extension setting affects the scope of interpretation. Participants continued blinded assignments from an earlier study, and the analysis concerns a defined group of Japanese adults with available endpoint data. Planning illustrations based on the observed effect are not the original trial’s design justification. Distinguishing the observed study result, the recalculated summaries, and hypothetical planning scenarios is essential to a statistically responsible reading.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several limitations specific to this registry record constrain interpretation. The study is an extension of Study APD334-302, with participants continuing the same blinded assignment, rather than a standalone treatment initiation. The results therefore describe the extension cohort and its Week 40 assessment. The registry record does not establish how representative these participants are of other people with ulcerative colitis or of participants who did not enter the extension.

The total enrollment was 42, and the primary outcome analysis included 14 participants in the placebo group and 28 in the etrasimod group. These group sizes limit precision, as reflected by the primary confidence interval. The analysis population further includes only participants with outcome data available at the specified time point. The amount and pattern of missing data, reasons for missingness, and methods used to address it are not reported in the registry record.

The primary endpoint is a composite definition based on symptoms and endoscopy. Component-level outcomes and participant-level data are not reported in the registry record, limiting assessment of how each component contributed to the overall remission percentage. The sponsor’s detailed analysis method, multiplicity plan, interim analyses, and original sample-size justification are also not reported. The posted secondary results cover only three of the five listed secondary outcomes.

Finally, the safety figures are counts in a small extension cohort. The registry entries do not provide the detail needed to assess event timing, causality, or comparative safety with precision. These limitations do not negate the posted results, but they restrict what can be concluded from them.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Oral Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis in Adult Japanese Participants (ELEVATE UC 40 JAPAN) — NCT04706793.
• Registry record last updated 2023-10-16; status last verified 2023-09.
• Results first posted 2023-10-16.
• 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.

23. Record Summary

NCT04706793 is a completed Phase 3, randomized, double-blind, parallel-group, placebo-controlled, 40-week extension study of oral etrasimod 2 mg versus placebo in Japanese adults with moderately to severely active ulcerative colitis. Participants continued their blinded treatment assignments from Study APD334-302, for a stated total treatment duration of 52 weeks across the two studies.

For the primary outcome at Week 40, the registry reports clinical remission in 25.0% of 28 analyzed etrasimod participants and 7.1% of 14 analyzed placebo participants. The risk difference was 17.86 percentage points, with a 95% confidence interval from -3.10 to 38.82. The interval includes zero, and the recalculated unadjusted p-value is 0.165. The numerical results support a description of the observed group contrast, while leaving uncertainty about its magnitude and direction.

The registry also posts numerical results for three secondary outcomes and safety counts. Further details about the full statistical plan, multiplicity, and missing-data handling are not reported in the registry record.