Efficacy and Safety of Inhaled AZD1402 Administered for Four Weeks in Adults With Asthma on Medium-to-High Dose Inhaled Corticosteroids: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Inhaled AZD1402 Administered for Four Weeks in Adults With Asthma on Medium-to-High Dose Inhaled Corticosteroids (NCT04643158), a randomized phase 2 study. The primary outcome is Part 1: Number of Participants With Adverse Events (AEs).

2. Clinical Question

The two-part structure reflects different treatment backgrounds and asthma-control populations, so the Part 1 and Part 2 safety counts should be read in their own context. The central reported question is whether adverse events were observed during the stated assessment period; the record does not provide a single summary contrast that quantifies a difference between AZD1402 and placebo.

3. Trial Design

This was a phase IIa randomized, double-blind, placebo-controlled, parallel-group, multi-centre study of inhaled AZD1402. The registry record lists enrollment as 72 and status as terminated. The start date was 2021-03-12, and the primary completion date was 2023-07-20. The reason for termination is not reported in the registry record.

The study had two parts. Part 1 included a lead-in cohort for each dose level to assess safety and pharmacokinetics in adults with asthma controlled on medium-dose ICS-LABA before progression to dosing in Part 2. Part 2 concerned adults with asthma uncontrolled on medium-to-high-dose ICS-LABA. The brief description states that Part 2 would begin following evaluation of safety and pharmacokinetics at the relevant dose level in Part 1a. This staged approach means the parts involved different patient groups and were not simply duplicate comparisons in the same population.

In Part 1, the listed groups were AZD1402 Dose 1, Dose 2, Dose 3 and placebo. In Part 2, the listed groups were Dose 1, Dose 2 and placebo. Randomization and double masking were reported; the registry record does not give additional details about the randomization procedure or how masking was maintained.

For each participant, the stated overall study period was approximately 3.5 months, comprising a 2-week Screening Period, a 4 week Run-in Period, 4 weeks of Treatment Period and 4 weeks of Follow-Up Period. The primary safety outcome was assessed from Screening (Week -6) until Follow-up (Day 56). These time descriptions refer to different aspects of the study timeline and do not change the stated four-week treatment duration.

The registry lists a range of pharmacokinetic and immunogenicity secondary outcomes, including serum concentration measures and antidrug antibodies. It also lists 26 outcome measures and 4 analyses. The detailed efficacy outcomes and their results are not reported in the registry record for this 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: The screening period was of 2 weeks (Week -6 to Week -4) for both parts of the study. Informed Consent Form (ICF) was signed prior to screening procedures. All the study assessments were performed as per the schedule of assessment. Participants who met the eligibility criteria were randomized to study intervention in addition to receiving background local standard of care therapy.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety set included all patients who were randomised and received any investigational product (IP).

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: The full analysis set included all patients who were randomised and received any investigational product (IP).

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Number of Participants With Adverse Events (AEs), measured over From Screening (Week -6) until Follow-up (Day 56).

The primary endpoint was the number of participants with adverse events in Part 1. An adverse-event count is a safety measure: it records how many participants experienced an event during the specified observation period, rather than measuring the frequency or duration of every event. The registry specifies the assessment window as Screening (Week -6) until Follow-up (Day 56), and describes the endpoint as evaluating AZD1402 safety and tolerability compared with placebo at different dose levels in adults whose asthma was controlled on medium-dose ICS-LABA.

Safety endpoints are used in trials because a treatment can be assessed not only by its intended clinical effects but also by events occurring during exposure and follow-up. Counts can make an initial description of the experience in each group. By themselves, however, they do not establish that an event was caused by study treatment, nor do they convey event severity, duration, or clinical importance unless those details are separately reported.

The record defines the safety set as all randomized participants who received any investigational product. The adverse-event information includes serious-event counts and counts in an other-adverse-event category, across both study parts. Those listings provide useful context, but the registry record does not present a single numerical primary comparison, an effect estimate with a confidence interval, or a statistical test for the Part 1 primary endpoint. A separate primary efficacy measure is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial results can be described in several ways. A count tells how many participants met an event definition; a proportion relates that count to the number at risk; an effect estimate compares groups; and an uncertainty interval indicates how compatible a range of effects is with the observed data under a statistical model. The registry entries report group counts and numbers at risk for adverse events, but do not provide confidence intervals or a primary group-comparison estimate. The counts can therefore be read as descriptions of what was recorded, not as precise estimates of comparative risk.

What does randomization contribute?

Random allocation is intended to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics. This supports a fair comparison when allocation is implemented as planned and participants are analyzed appropriately. Randomization does not guarantee that groups will be identical, particularly when group sizes are limited. The registry record identifies the allocation as randomized, but does not report the allocation sequence method, concealment procedure or other operational details. Those methods are not reported in the registry record.

Double masking can reduce the influence of knowledge of treatment assignment on participant reporting, clinical care and outcome assessment. The record labels the trial double-blind but does not state which roles were masked or how masking was maintained. The placebo was described as matching placebo administered by inhalation. No further masking details are reported in the registry record.

How should event counts be understood?

For binary outcomes such as whether a participant experienced an event, each participant is classified according to whether the event occurred during the defined period. A count of participants with an event is different from a count of all event episodes: one participant may experience more than one event, but the participant count records that person as having an event. The primary endpoint is explicitly described as a number of participants with adverse events. The safety results separately list serious adverse events and other adverse events.

Comparing raw counts alone can mislead when group sizes differ. A proportion uses the number at risk as its denominator, but even proportions can be uncertain when based on few participants. The reported group sizes in this trial are modest, particularly in some Part 2 groups, so individual observations can have a visible effect on a group summary. A confidence interval would communicate sampling uncertainty around an estimate; the registry entries do not report such intervals for the adverse-event results. No new interval or test can be derived from the record without making additional analytical choices.

What does a confidence interval mean?

In general, a confidence interval is a range produced by a statistical procedure that reflects uncertainty in an estimate under its assumptions. It is not a guarantee that the true value lies in the interval, and it does not measure the probability that a particular treatment effect is true. For trial interpretation, the width matters: a wide interval indicates that the data are compatible with a broader range of effects. Here, no interval is reported for the primary safety endpoint, so the precision of a comparative effect cannot be evaluated from an interval.

Why can over-dispersion matter?

General statistical note: count outcomes are sometimes analyzed with models that assume a particular relationship between the mean and variability. Over-dispersion means that observed variability exceeds what a model assumes. If it is ignored, standard errors may be too small and statistical uncertainty may be understated. This concept is relevant to some event-count analyses, but the primary endpoint in this trial is a participant count, and no over-dispersion analysis or count model is reported in the registry record. It would not be appropriate to infer that such a model was used.

What can planning calculations tell us?

A sample-size calculation is a planning exercise that asks how much information a future study might need under stated assumptions. It is distinct from observed power, which is not a useful substitute for describing an estimate and its uncertainty after results are available. The planning illustration associated with these results is described as using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and an effect set to a stated fraction of an observed effect. It is explicitly not the trial's own design calculation. A sample-size illustration does not show that the trial had a particular probability of detecting an effect, and it does not establish that a treatment effect is real. The planning assumptions and illustration do not replace the missing inferential results for the trial's primary safety endpoint.

The registry record does not report the detailed statistical model, a formal hypothesis test for the primary endpoint, a prespecified adjustment for baseline covariates, or a confidence-interval method. Those methods are not reported in the registry record. Accordingly, the posted adverse-event counts support descriptive interpretation, while stronger claims about comparative effects or statistical significance cannot be made from these registry entries.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 26 outcome measures and 4 analyses, including safety, pharmacokinetic and immunogenicity measures. When a study assesses multiple outcomes or makes multiple comparisons, the chance of at least one apparently notable result can increase if each is tested without accounting for the number of tests. Methods for addressing this issue may include designating a primary endpoint, specifying a testing sequence, or adjusting inference across comparisons. These are general statistical approaches; the registry record does not report whether any multiplicity procedure was planned or used.

The primary outcome is identified as the number of participants with adverse events in Part 1. However, no single primary comparison, test result or uncertainty interval for that endpoint is reported in the registry entries. The reason that one primary result is not presented is not reported in the registry record. The record also does not provide enough detail to determine how the listed analyses relate to any prespecified testing hierarchy.

Missing-data handling is not reported in the registry record. In general, missing outcome information can affect estimates if participants with missing observations differ from those with complete data. The registry entries do not state how missing adverse-event information, withdrawal or incomplete follow-up was handled, or whether sensitivity analyses were performed. No assumptions about missingness or imputation should therefore be attributed to this trial.

The safety population is defined as all randomized participants who received any investigational product. This is a treatment-exposed safety set, rather than a statement that every randomized participant was included regardless of exposure. The record does not describe additional analysis populations or provide a participant-flow account in the registry record for this analysis. Consequently, the relationship between the listed safety groups and any other analysis population is not reported in the registry record.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthma (11.1%).

Serious adverse events were recorded for none of the listed Part 1 groups, while Part 2 Dose 2 had 1 serious adverse event among 9 participants. No deaths were reported in any listed group. The registry identifies Asthma among the top serious-event terms at 11.1%, but the registry entries available for this analysis do not specify the group associated with that term. This term-level figure should not be treated as a complete summary of all serious events.

The other-adverse-event counts were 4 of 11, 6 of 10, 10 of 13 and 8 of 16 across the Part 1 Dose 1, Dose 2, Dose 3 and placebo groups. In Part 2, the corresponding counts were 3 of 4, 5 of 9 and 6 of 9 for Dose 1, Dose 2 and placebo. These counts describe participants with an event in the category; they do not show the number of event episodes or establish that treatment caused an event.

Rare or absent events in groups with limited numbers of participants do not rule out risk. The registry does not report uncertainty intervals, event-level detail, relatedness assessments or a comparative safety test in the registry record for this analysis. Part 1 and Part 2 also concern different asthma-control populations, so their counts should not be pooled or directly treated as like-for-like comparisons.

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

The record documents a randomized, double-blind, placebo-controlled study with a stated focus on safety and tolerability in Part 1 and with safety and pharmacokinetic evaluation across two parts. The adverse-event listings show that participants in each group were recorded in the other-adverse-event category. Serious adverse events were recorded in one of the listed groups, and no deaths were reported. These observations characterize what the registry lists; they do not establish a causal treatment effect.

The results do not show whether AZD1402 improves asthma control. Although the study title refers to efficacy and safety, the primary outcome described in the registry record is a safety endpoint, and a specific efficacy endpoint result or treatment-effect estimate is not reported in the registry record. The absence of such information cannot be interpreted as evidence for or against efficacy.

Likewise, the serious-event counts do not establish that a dose is safer or less safe than placebo. The groups differ in size, and the two parts involve different asthma-control populations and treatment backgrounds. Without a prespecified comparison, uncertainty estimates and details of event assessment, descriptive differences should not be turned into a definitive ranking.

The trial's terminated status is a registry fact, but the reason for termination is not reported in the registry record. Termination alone does not explain whether recruitment, safety, efficacy, operational factors or another circumstance determined the decision. No such explanation should be inferred.

Overall, the record offers a limited descriptive account of adverse events during a study with four weeks of treatment and a stated follow-up period. It does not supply the inferential results needed to establish the size or precision of comparative safety effects, nor the efficacy outcomes needed to answer a treatment-benefit question. Interpretation should remain within those boundaries.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why study structure and population definitions matter when reading clinical results. Although both parts examined inhaled AZD1402 against placebo, Part 1 concerned adults whose asthma was controlled on medium-dose ICS-LABA, while Part 2 concerned adults whose asthma was uncontrolled on medium-to-high-dose ICS-LABA. A comparison across the parts would therefore mix treatment differences with differences in the populations and study context.

The dose-ranging structure also needs careful interpretation. Part 1 lists three AZD1402 dose levels, whereas Part 2 lists two. The groups are not all the same size, and some contain few participants. In small groups, estimates based on participant counts can be sensitive to the experience of individual participants. That makes transparent reporting of denominators, uncertainty intervals and analysis methods particularly valuable.

The registry record also illustrates the distinction between a named primary endpoint and a reported comparative result. It identifies a Part 1 adverse-event endpoint and defines a safety population, but the registry entries available do not include a single primary estimate or its precision. Without those items, readers can describe the observed group counts but cannot assess the statistical strength of a comparative claim.

Finally, a two-part, staged study can provide different kinds of information: safety and pharmacokinetic evaluation in a lead-in context, followed by evaluation in a different asthma-control group. That design feature is relevant to interpretation, but it does not by itself demonstrate benefit or establish the generalizability of the findings. Clear reporting of efficacy results, missing-data methods, multiplicity handling and reasons for termination would be needed for a fuller statistical assessment; those details are not reported in the registry record.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to interpreting this record. First, the study is listed as terminated, but the reason is not reported in the registry record. Without that context, the status cannot be linked to a particular result or event. The record also gives no single primary comparison or inferential estimate for the stated Part 1 safety endpoint, so the precision of a treatment contrast cannot be assessed.

Second, the parts involve different asthma-control populations and different listed dose groups. Part 1 includes Dose 3, while Part 2 does not. The study therefore does not provide matching dose-group structures across the parts, and the group counts should not be interpreted as a single continuous dose-response comparison across both populations.

Third, the number of participants in several listed groups is limited. That makes descriptive counts potentially sensitive to individual outcomes and leaves uncertainty difficult to judge in the absence of confidence intervals. The registry entries do not provide event-level descriptions, severity breakdowns beyond serious versus other events, or a comparative analysis of adverse-event risk.

Fourth, the treatment period was four weeks, with follow-up described as four weeks and the overall participant study period as approximately 3.5 months. These time windows characterize the reported observation context; they do not establish what might occur outside it. The record does not provide longer-term safety results in the registry record for this analysis.

Finally, missing-data procedures, multiplicity handling, detailed statistical methods, and the results of specific efficacy outcomes are not reported in the registry record. The absence of those details limits both causal interpretation of the safety counts and evaluation of efficacy.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of Inhaled AZD1402 Administered for Four Weeks in Adults With Asthma on Medium-to-High Dose Inhaled Corticosteroids — NCT04643158.
• Registry record last updated 2025-08-28; status last verified 2025-08.
• Results first posted 2025-08-28.
• 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.

18. Record Summary

The registry record describes NCT04643158, a phase IIa, randomized, double-blind, placebo-controlled, parallel-group, multi-centre study of inhaled AZD1402 in adults with asthma. It lists enrollment as 72 and status as terminated. The study had two parts: Part 1 involved adults whose asthma was controlled on medium-dose ICS-LABA, and Part 2 involved adults whose asthma was uncontrolled on medium-to-high-dose ICS-LABA.

The stated primary outcome was the number of participants with adverse events in Part 1, assessed from Screening (Week -6) until Follow-up (Day 56). The safety set included randomized participants who received any investigational product. The record lists serious and other adverse-event counts by dose group and placebo, but does not provide a single primary comparison or confidence interval in the registry record for this analysis.

The record lists pharmacokinetic and immunogenicity secondary outcomes. Specific efficacy results, missing-data methods, multiplicity procedures, detailed statistical methods and the reason for termination are not reported in the registry record.