A Study of Single Ascending Doses of IW-3300 in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Single Ascending Doses of IW-3300 in Healthy Volunteers (NCT05188261), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

The study addresses early safety and tolerability, rather than whether IW-3300 improves a health outcome. Its sequential design proceeds through dose cohorts, with safety reviews before moving to a higher dose. The brief summary says that up to 5 different doses would be studied, while the posted arm descriptions list four IW-3300 dose groups.

The primary endpoint counts participants who experienced at least one qualifying treatment-emergent adverse event. It does not count the total number of separate events, nor does it summarize symptom severity or duration. The record also reports serious adverse events and deaths by group, but those are separate safety summaries. No efficacy outcome or treatment-benefit question is identified in the posted results.

3. Trial Design

This is a randomized, triple-masked, sequential Phase 1 study of rectally administered IW-3300 in healthy volunteers. The registry record lists the study as completed and reports enrollment of 32. The listed intervention groups are placebo and single doses of IW-3300 at 100 μg, 300 μg, 900 μg and 2500 μg.

The brief summary describes a 3:1 randomization ratio for active drug versus placebo and says that safety reviews would take place before proceeding to each higher dose. The arm descriptions list 6 participants in each active-dose group and 2 in each corresponding placebo group. The design is therefore organized around dose cohorts, rather than a single pooled active-treatment group. The registry record does not report whether any dose cohort was added beyond the listed groups.

IW-3300 was administered as a low-volume 20 mL enema. The study dates recorded are a start date of 2022-01-18 and a primary completion date of 2022-03-09. These dates and the completed status describe the trial record; they do not establish what happened to participants outside the outcomes reported.

The record does not report a sample-size justification, a formal hypothesis-testing plan, or a detailed account of the safety-review decisions. It also does not explain how masking was implemented or whether masking was assessed. The posted arm-level outcome results should therefore be read as the available descriptive safety data, not as evidence of a prespecified comparative efficacy analysis.

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: As pre-specified by the statistical analysis plan, for the analyses reported herein, data from the 2 participants dosed with placebo in each of the 4 cohorts were pooled into a single placebo group (N=8).

Overall Study

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), measured over From first dose of study drug through 24 hours post-Day 1 dose.

The primary endpoint is the number of participants with treatment-emergent adverse events, or TEAEs. The registry defines an adverse event as an untoward medical occurrence temporally associated with study intervention, whether or not it is considered related to that intervention. An AE is classified as treatment-emergent if it starts after initial study-drug administration and within 1 day of the last dose.

The stated timeframe is from the first dose through 24 hours post-Day 1 dose. Because the study evaluates single ascending doses, this endpoint captures events beginning during the defined early observation period after dosing. The measure is a participant count: a participant is counted as having a TEAE, rather than the outcome counting every occurrence of every event.

Early-phase studies commonly use safety outcomes to describe tolerability and identify events for further review during dose escalation. This is a general explanation of the endpoint's role, not a claim about the study's unreported analysis plan. A count alone does not communicate the event's seriousness, clinical details, duration, or relationship to treatment. The registry reports separate serious-event summaries, but does not provide event-level descriptions in the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is binary at the participant level: each participant either had at least one qualifying TEAE during the defined period or did not. The registry reports the number of participants with the event in each group. This is a count outcome, not a continuous measure such as a laboratory value, and not a tally of every adverse-event episode.

What does a group count tell the reader?

A group count describes how many participants met the endpoint within that group. The registry also reports the number of participants represented in each group, which gives context for the count. A count should be read as a finite-sample observation, not as the exact underlying probability of an event in all people who might receive the intervention. General statistical reasoning applies: uncertainty is greater when estimates are based on small groups, and a single participant can have a substantial influence on a group summary.

The posted values do not include confidence intervals. In general, a confidence interval describes a range of values compatible with the data under a specified statistical method and its assumptions. It helps distinguish an imprecise estimate from a more precise one. Without a posted interval or other comparative estimate, the reader cannot assess the uncertainty around differences between these groups from the registry outcome alone.

Why is there no reported two-arm comparison?

The registry record indicates that values were missing or not estimable for a two-arm comparison of this binary endpoint, and it reports no analyses. A descriptive count can still be listed for each arm when a comparative result is unavailable. These are different kinds of information: group summaries describe the observed data, while an inferential comparison quantifies the estimated contrast and its uncertainty under an analysis method.

No test, model, adjustment, confidence interval, or p-value for the primary outcome is reported. The record does not identify a statistical analysis population for that outcome, either. It would therefore be inappropriate to assign a particular method to the trial or to interpret the raw counts as if a formal comparison had been carried out.

How should the sequential design affect interpretation?

In general, a sequential dose-escalation design studies dose groups in an ordered process, with review between stages. The brief summary says that safety reviews would be conducted before proceeding to each higher dose. This matters when interpreting group patterns: the record does not describe a single fixed comparison across all doses or the rules governing progression. It does not report whether the review changed the study conduct, the dose sequence, or the number of cohorts.

The listed dose groups can be read individually. They should not be combined into a single active-treatment estimate unless an analysis specifying that combination is reported. No such pooled analysis appears in the registry results. Likewise, the displayed counts do not establish a dose trend; no trend test or dose-response model is reported.

What do the planning illustrations represent?

In general, a sample-size planning calculation asks how many participants might be needed to detect a specified effect under chosen assumptions. The record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes illustrations for detecting stated fractions of the observed effect. These are planning assumptions, not the trial's reported design justification.

Such illustrations do not measure the trial's observed power. Observed power is not a substitute for reporting the estimate and its uncertainty; a calculation based on the observed effect may simply reflect the same imprecision as the result. The registry record does not report that these planning assumptions were used to design this trial, and the illustrations should not be read as evidence that the study was adequately sized for a particular safety comparison.

In general, the normal approximation is a mathematical simplification used for some sample-size calculations. Its suitability depends on the analysis setting and assumptions. For binary outcomes with sparse counts, approximate methods may not represent uncertainty especially well. The registry record does not report that a normal-approximation inferential test was used for the posted TEAE results; the assumption is stated for planning illustrations only.

What is and is not available for interpretation?

The registry provides group counts for the primary endpoint and separate group summaries for serious adverse events and deaths. It does not provide an analysis of comparative effects, event-level descriptions, confidence intervals, or a detailed statistical plan. General principles can explain why these elements matter, but they cannot fill gaps in the trial record. The sound reading is limited to the reported counts and the definitions and timeframe attached to them.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Placebo", "100 μg IW-3300", "300 μg IW-3300", "900 μg IW-3300", "2500 μg IW-3300")
n      <- c(8, 6, 6, 6, 6)
events <- c(2, 1, 0, 1, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Placebo  8  2  25.0  3.2  65.1  7.1  59.1  7.5  60.0
ARM  100 μg IW-3300  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  300 μg IW-3300  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  900 μg IW-3300  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  2500 μg IW-3300  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures and 0 posted analyses. It identifies the TEAE count as the primary outcome, but does not report a multiplicity strategy or explain how any additional outcome measure was handled in the analysis. Multiplicity refers, in general, to the increased chance of a false-positive finding when several hypotheses are tested. A prespecified strategy may address that issue; no such strategy is reported in the registry record.

The record does not report how missing outcome data were handled, whether all randomized participants were included in the primary summary, or how participants who did not complete the observation period were treated. It also does not identify a named analysis population for the posted primary result. These details matter because decisions about missing observations and analysis populations can affect both the denominator and interpretation of a group summary.

The endpoint counts are posted with group participant counts, but the registry does not provide a missing-data account or a participant flow description tied to this outcome. No imputation method, sensitivity analysis, or missingness assumption is reported. It would be inappropriate to assume that there were no missing observations simply because group counts are displayed.

The record does not report interim statistical analyses or a formal statistical plan for stopping or proceeding between dose groups. It does state that safety reviews would take place before higher doses. That description should not be taken as evidence of a particular interim-testing procedure, multiplicity adjustment, or stopping boundary.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in the placebo group and in each listed IW-3300 dose group. It also reports zero deaths in each group. These are the posted serious-event and death counts for the recorded groups; they do not establish that serious events or deaths are impossible, or that a larger or longer study would necessarily have the same findings.

The registry separately reports other, non-serious adverse events affecting 2 participants in the placebo group, 1 in the 100 μg group, 0 in the 300 μg group, 1 in the 900 μg group and 2 in the 2500 μg group. Those figures are distinct from the serious-event counts. The serious-event summary lists no top serious-event terms.

In general, a serious adverse event is a category based on seriousness criteria, not simply a description of symptom intensity. The registry record does not include event-level narratives or additional details that would explain the circumstances of the reported events. The counts should therefore be read as safety summaries, not as a complete clinical characterization of each event.

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

The results describe the number of participants recorded with TEAEs after a single dose of IW-3300 or placebo during the registry's specified early observation period. The primary endpoint is a safety measure, and the posted counts are descriptive. They offer a record of what was observed in these study groups, not a definitive estimate of the safety profile in broader populations.

The counts do not establish that IW-3300 caused or prevented any event. The registry definition includes events whether or not considered related to the intervention. Without event-level descriptions and a reported comparative analysis, the record does not show the nature of the TEAEs, their severity, or whether investigators judged them related to treatment.

The results also do not establish efficacy. The posted primary outcome concerns adverse events, and no efficacy outcome is described in these results. A count of 0 in a dose group is an observation in that group during the stated timeframe, not proof of no risk. Likewise, counts that differ between groups do not on their own show a meaningful difference between treatments.

Because the trial involved healthy volunteers, a single-dose administration and a defined short-term safety window, the findings do not directly characterize repeated dosing, long-term exposure, or use in patients. The registry record does not report evidence that would answer those questions. The results are best understood within the scope of the study population, intervention, comparator and observation period recorded.

14. Why This Trial Matters Statistically

Early-phase dose-escalation studies have a statistical role distinct from trials designed to estimate clinical benefit. They characterize early safety observations and inform decisions about whether further study is warranted. In this trial, the registry describes sequential dose cohorts and safety reviews before moving to higher doses. That context is important when reading the arm-specific counts: the design is organized around staged exposure rather than a large confirmatory comparison.

The study also illustrates why raw counts need careful interpretation. The outcome is binary and the groups are small, so the observed count in a group can be sensitive to the experience of an individual participant. Reporting the counts transparently is useful, but a comparative conclusion requires more than noticing that group values differ. An estimate of the contrast and its uncertainty would be needed for a formal comparison, and the registry record does not report one.

The posted serious-event and death summaries add a separate safety perspective, but zero reported events within these groups cannot rule out uncommon risks. This is a general limitation of small early-phase studies, rather than a claim that such risks occurred in this trial. The record's narrow population and short observation window also define the scope of what can be learned.

Statistically, the trial matters as an example of descriptive safety evidence in a sequential design. Its registry results should not be mistaken for a precise estimate of treatment effects, proof of safety, or evidence of efficacy. Those boundaries are central to a responsible reading of early-phase clinical data.

15. 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 results are group counts without a reported comparative estimate, confidence interval or p-value. The registry explicitly indicates that the binary two-arm comparison is unavailable because values were missing or not estimable, and it lists no posted analyses. Consequently, the precision of any contrast cannot be evaluated from the registry outcome alone.

The study groups are small, and the record does not provide event-level descriptions for the TEAEs. The posted counts cannot show what events occurred, their severity or duration, or how investigators assessed their relationship to study intervention. Although the record reports serious adverse events and deaths separately, those summaries do not replace a detailed account of non-serious events.

The study concerns healthy volunteers receiving a single rectal dose, with the primary outcome timeframe ending 24 hours post-Day 1 dose. Its results do not describe longer exposure or populations with the conditions for which a treatment might eventually be studied. The registry record does not report outcomes that would support an efficacy conclusion.

Details needed to assess missingness and analysis choices are not reported in the registry record. This includes a description of the analysis population, missing-data handling, multiplicity approach, and a full statistical plan. The sequential safety-review process is mentioned, but its decision criteria and consequences are not described. These gaps limit interpretation of how the posted group results relate to the trial's conduct and intended analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Single Ascending Doses of IW-3300 in Healthy Volunteers — NCT05188261.
• Registry record last updated 2023-12-08; status last verified 2023-03.
• Results first posted 2023-12-08.
• 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.

19. Record Summary

NCT05188261 is a completed, randomized, triple-masked, sequential Phase 1 study of single ascending rectal doses of IW-3300 in healthy volunteers. The record lists enrollment of 32 and four active-dose groups: 100 μg, 300 μg, 900 μg and 2500 μg, alongside placebo. The intervention was described as a low-volume 20 mL enema, with safety reviews before proceeding to higher doses.

The primary endpoint was the number of participants with TEAEs from first dose through 24 hours post-Day 1 dose. The registry posts group counts but no inferential analyses, and states that a two-arm comparison was unavailable because values were missing or not estimable. Serious adverse events and deaths were reported as zero in each group. The record does not report a detailed statistical plan, missing-data method, or event-level descriptions.