SAD, MAD and Food Effect Evaluation of Safety, Tolerability, and PK of AQ280 in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SAD, MAD and Food Effect Evaluation of Safety, Tolerability, and PK of AQ280 in Healthy Subjects (NCT05485779), a randomized phase 1 study. The primary outcome is Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant.

2. Clinical Question

3. Trial Design

This completed phase 1 trial was randomized, double-blind, placebo-controlled and sequential. It enrolled 66 healthy subjects. The registry lists a start date of 2022-07-20 and a primary completion date of 2023-07-10. The study title describes single and multiple ascending doses and a food-effect evaluation; its stated principal aim was to obtain safety, tolerability and pharmacokinetic (PK) data for AQ280.

Part A was the single ascending dose (SAD) portion. Its posted groups include fasted placebo and AQ280 cohorts, a fed placebo cohort, and a fed AQ280 cohort at 16 mg. The listed fasted AQ280 doses were 3 mg, 9 mg, 16 mg, 48 mg and 60 mg. Part B was the multiple ascending dose (MAD) portion, with placebo and AQ280 at 9 mg, 27 mg and 60 mg. The arm descriptions state that Part B dosing was once daily for seven days. Several original arm descriptions use “TBD,” while posted safety groups name the doses above. The registry does not explain the sequence or decision rules used to move between cohorts.

Sequential dose cohorts are a feature of this design: cohorts are considered in an ordered program rather than as a single parallel comparison across all dose groups. Randomization and double blinding are also stated, but the registry record does not report the allocation ratio, the randomization procedure, or who was masked. The number enrolled is not necessarily the number contributing to every endpoint; the registry reports group-specific safety populations for the posted outcomes. The record does not report the sample-size justification or a detailed participant flow.

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.

Only the first 6 of 11 groups are shown.

Treatment Period 1 (Fasted)

Reasons for not completing this period:

Treatment Period 2 (Fed Groups Only)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population. The 'Part A (SAD): Placebo (Fasted)' cohort includes the 8 participants in the fasted only cohort as well as any AEs experienced by the 2 participants in the 'Part A (SAD): Placebo (Fasted/Fed)' cohort whilst in the fasting during Treatment Period 1. Any AEs experienced by these 2 participants during Treatment Period 2 (ie, the fed stage) only are listed separately under the cohort 'Part A (SAD): Placebo (Fed).

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: Safety Population

Only the first 6 of 12 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant, measured over Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts.

The posted primary endpoint for Part A is the number of participants who experienced a treatment-emergent adverse event (TEAE). It is expressed as a participant count, rather than as the number of events: a participant with more than one event is still counted as a participant who experienced a TEAE. This endpoint is used to describe the occurrence of treatment-emergent events during the specified observation period.

The timeframe is screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts. The reported counts are 1 of 10 for fasted placebo, 0 of 2 for fed placebo, 1 of 6 at 3 mg fasted, 2 of 6 at 9 mg fasted, 1 of 6 at 16 mg fasted, 2 of 6 at 16 mg fed, 0 of 6 at 48 mg fasted, and 1 of 6 at 60 mg fasted. These are descriptive counts from small cohorts; they do not by themselves establish a comparative effect.

As a safety endpoint, the count helps characterize how many participants had at least one event during observation. It does not convey event severity, duration, relatedness, or the number of distinct events. Those details are not reported in the primary endpoint summary. The registry also lists PK outcomes, but the primary endpoint is the Part A TEAE participant count.

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 experienced a TEAE during the relevant period or did not. The registry reports counts of participants with events and the number of participants in each group. A count is an intuitive summary, but it does not communicate the precision of an estimated event frequency. With small groups, a change in the status of a single participant can materially alter the observed count. The posted counts should therefore be read as descriptions of these cohorts, not as precise estimates for a broader population.

What a participant count captures

Counting participants with at least one event avoids treating repeated events in the same person as if they were separate people. That makes the endpoint useful for describing how many participants experienced an event, but it omits the number of events per participant. It also does not, on its own, describe event seriousness, severity, duration, or relationship to study drug. The registry provides a separate serious-event summary, but the primary endpoint’s description does not give those additional details for each TEAE.

Why group comparisons are limited

A comparison of event counts between groups ordinarily needs to account for both the number with an event and the group size. The groups in Part A are small and unequal in size, and the fasted placebo endpoint population has a stated overlap-related definition. In addition, fed and fasted status is relevant to the study’s food-effect evaluation. These features make a simple reading of raw counts as if all groups were directly interchangeable inappropriate. The registry record does not report a statistical model or a prespecified testing method for the primary safety count.

A confidence interval is a general statistical way to express uncertainty around an estimate: it gives a range of values compatible with the data under the method’s assumptions. No confidence interval for the primary endpoint is reported in the registry record. A p-value, when used, summarizes how incompatible data are with a specified null hypothesis under a statistical model; it is not a measure of clinical importance. No p-value for the primary endpoint is reported either. Without a reported inferential analysis and its assumptions, the counts support descriptive interpretation, not a claim of statistical separation.

Over-dispersion and event counts

Over-dispersion is a general concern when analyzing event counts: it means observed variability exceeds what a chosen count model expects. It can arise when participants differ in their underlying propensity for events or when events cluster. The primary endpoint is the number of participants with at least one event, rather than a repeated-event count, and the registry does not report a model that assesses over-dispersion. This concept should not be mistaken for a finding in this study.

Recalculation and planning illustrations

The registry-derived two-arm binary comparisons are marked as unavailable because values are missing or not estimable. There are therefore no recalculated comparisons to interpret. The general planning description in the registry specifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. It also distinguishes participants per arm for ordinary outcomes from total events for time-to-event outcomes. No planning values for this binary endpoint are included in the information. Any sample-size illustration, where available, is a planning exercise based on assumptions, not observed power and not a description of the trial’s actual design justification.

PK outcomes and analysis detail

The registry lists PK outcomes for AQ280 and its main metabolite AQ282, including area under the concentration-time curve and maximum observed concentration, as well as food-effect and multiple-dose measures. It records 21 outcome measures and 14 analyses, with 11 secondary outcomes noted as posted. The numerical PK estimates, their uncertainty, and the methods used to analyze them are not reported in the registry record. The record also does not report transformations, covariate adjustments, missing-data methods, or analysis software. Those details should not be inferred from the outcome names alone.

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("Part A (SAD): Placebo (Fasted)", "Part A (SAD): Placebo (Fed)", "Part A (SAD): 3 mg (Fasted)", "Part A (SAD): 9 mg (Fasted)", "Part A (SAD): 16 mg (Fasted)", "Part A (SAD): 16 mg (Fed)")
n      <- c(10, 2, 6, 6, 6, 6)
events <- c(1, 0, 1, 2, 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  Part A (SAD): Placebo (Fasted)  10  1  10.0  0.3  44.5  1.8  40.4  2.3  41.3
ARM  Part A (SAD): Placebo (Fed)  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Part A (SAD): 3 mg (Fasted)  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Part A (SAD): 9 mg (Fasted)  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  Part A (SAD): 16 mg (Fasted)  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Part A (SAD): 16 mg (Fed)  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 lists 21 outcome measures and 14 analyses, and notes 11 secondary outcomes as posted. The listed secondary outcomes cover PK parameters for AQ280 and AQ282, differences between fed and fasted states, and multiple-dose measures such as accumulation ratio and area under the concentration-time curve over a dosing interval. The registry record does not report how many hypotheses were formally tested, whether any were designated confirmatory, or how multiplicity was handled. Without that information, the listed outcomes should not be treated as a single family of statistically controlled tests.

Multiplicity is a general issue when many outcomes or comparisons are examined: the chance of obtaining apparently unusual results can increase if many tests are considered without an adjustment or an interpretation plan. Whether adjustment is appropriate depends on the study aims and analysis strategy. No adjustment method or hierarchy of outcome testing is reported in the registry record, so it is not possible to determine how the trial’s investigators addressed this issue.

The record does not report a missing-data method, imputation strategy, or sensitivity analysis. It also does not give a complete account of exclusions or withdrawals by endpoint. The stated safety population and the group-specific denominators identify who contributed to the posted safety summaries, but they do not describe missingness for every outcome. The primary endpoint is a participant count; its reported group sizes should not be assumed to apply to the PK outcomes or every analysis.

Analysis populations are described only in limited terms. The Part A primary safety endpoint refers to a safety population, and its fasted placebo definition includes a specified contribution from the fasted/fed placebo cohort during Treatment Period 1. The registry record does not report a full set of analysis-population definitions or the treatment of participants with incomplete observations. These omissions limit reconstruction of the analysis and prevent assumptions about how missing values or protocol deviations were handled.

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 serious adverse-event summary reports zero serious adverse events and zero deaths in every listed group. In Part A, the groups include fasted placebo, fed placebo, and the listed fasted or fed AQ280 dose cohorts. In Part B, placebo and AQ280 groups at 9 mg, 27 mg and 60 mg are listed. The number at risk is also given by group, ranging from 2 in the fed placebo group to 10 in the fasted placebo group in Part A, and from 6 to 7 in the listed Part B groups. These figures describe the registry’s reported safety groups; they do not establish that the underlying risk is zero.

Zero observed serious events means none were recorded in these groups during the reported study observation. It does not show that serious events could not occur, especially when group sizes are small. The registry lists other adverse events separately: Part A counts range from 0 to 2 participants by group, and the Part B counts are 3 in each listed group. These other-event counts should not be conflated with serious events or with the primary endpoint’s Part A count. The registry record does not provide event terms in the serious-event summary, and its serious-event term list is empty.

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

The posted results give a descriptive account of safety observations across the listed AQ280 and placebo cohorts. In Part A, participant counts with at least one TEAE range from none in the fed placebo and 48 mg fasted groups to 2 in the 9 mg fasted and 16 mg fed groups. The small group sizes, different food conditions, and the stated composition of the fasted placebo population all matter when comparing these numbers. They do not support a simple dose-response conclusion, and no inferential comparison is reported for the primary endpoint.

The serious-event summary records zero serious adverse events and zero deaths in all listed groups. That is a report of observed events in this trial, not proof that the risk of such events is absent. The separate other-event counts document events in both the single- and multiple-dose parts. The summaries do not provide enough detail to characterize event type, severity, duration, or causality beyond what is stated in the registry.

The trial’s stated objective included collecting PK information alongside safety and tolerability data, with the intention of informing future studies in patients. The registry lists PK outcomes, but numerical PK results are not included in the information. The posted primary endpoint is a safety count, not a measure of symptom improvement or clinical benefit. Although EoE is listed as a condition, the enrolled participants are described as healthy subjects. The registry record therefore does not establish efficacy or safety in people with EoE.

In statistical terms, the result is limited by the descriptive nature of the available primary outcome summary, small cohorts, absent uncertainty estimates, and lack of reported analysis details. The data can be used to understand which event counts were recorded in these study groups. They cannot, on their own, establish a reliable comparative effect, identify a most suitable dose, or predict outcomes in a patient population. The registry’s stated purpose was to inform future studies; the posted safety counts should be interpreted within that early-stage purpose.

14. Why This Trial Matters Statistically

This trial is statistically notable for illustrating how early dose evaluation differs from a conventional large parallel-group comparison. It combines sequential cohorts, single-dose and multiple-dose parts, and fed and fasted conditions. Those features create several distinct descriptive questions: event occurrence across dose groups, safety during repeated dosing, and PK differences associated with food. Results from these questions should not be collapsed into a single comparison without accounting for their different populations and settings.

The primary safety endpoint is a participant count, which is readily understood but has limited precision when group sizes are small. A low or zero count can occur in a small cohort even when the underlying event probability is not zero. Conversely, a small change in observed participants with events can shift the apparent pattern. This is why the posted counts are useful as early descriptive information but are not a substitute for uncertainty estimates or appropriately designed later studies.

The registry also makes clear that the study’s goal was to collect safety, tolerability and PK information to support dose and regimen choices for future patient studies. That objective is different from testing clinical efficacy. Statistically, the central task is to interpret the available evidence at the level it supports: cohort-level safety observations and a planned PK evaluation, rather than a definitive treatment comparison. The limited outcome estimates and analysis details reported in the registry also show why transparent reporting of populations, missing data, and analysis methods is important when interpreting early clinical research.

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.

Several features limit interpretation of the posted safety counts. The study enrolled healthy subjects, while EoE is listed as a condition; the registry does not report outcomes in people with EoE. The primary endpoint is restricted to Part A, and the available description does not provide numerical primary endpoint results for Part B. Part A cohorts are small, and their sizes differ. The fed placebo cohort has 2 participants, while other groups have 6 or more. A count from such groups is sensitive to individual participant observations.

The fasted placebo population is described as including the 8 participants in the fasted-only cohort and any adverse events among the 2 participants in the fasted/fed cohort while fasting during Treatment Period 1. This makes the group’s definition important for interpretation and cautions against treating all listed groups as independent, directly comparable samples. The registry does not report further details about the crossover arrangement or how it was incorporated into statistical analysis.

The record does not report confidence intervals, p-values, adjusted comparisons, a sample-size justification, or a full statistical analysis plan for the primary endpoint. It also does not report missing-data methods, outcome-specific exclusions, or a complete participant-flow account. Numerical estimates for the listed secondary PK outcomes are not included in the information. The registry does not explain the dose-escalation sequence or decision rules, and arm descriptions for several cohorts use TBD even though the safety groups list dose levels. Finally, the available serious-event summary gives zero serious events and deaths but does not give detail about the other adverse-event terms. These limits mean the counts should be read as a narrow description of the posted groups, not as a complete assessment of safety or comparative effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: SAD, MAD and Food Effect Evaluation of Safety, Tolerability, and PK of AQ280 in Healthy Subjects — NCT05485779.
• Registry record last updated 2024-12-24; status last verified 2024-11.
• Results first posted 2024-12-24.
• 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.

19. Record Summary

The registry record describes a completed, randomized, double-blind, placebo-controlled phase 1 study of AQ280 in healthy subjects, with 66 participants enrolled. Its design was sequential and included a single ascending dose part, a multiple ascending dose part, and a food-effect evaluation. The registry lists eosinophilic esophagitis as a condition and identifies AQILION AB as the sponsor.

The primary posted outcome is the Part A count of participants experiencing a treatment-emergent adverse event, with different observation periods for fasted and fed/fasted cohorts. The listed Part A counts range from 0 to 2 by group. The serious adverse-event summary records zero serious events and zero deaths in all listed groups. The registry also lists PK outcomes, but numerical PK estimates and detailed analysis methods are not reported in the information.

The available results are descriptive and come from small, differently structured cohorts. They do not provide an inferential comparison for the primary safety endpoint or evidence of efficacy in patients with EoE.