To Assess the Safety, Tolerability and Pharmacokinetics of AZD5634 Following Inhaled and Intravenous (IV)Dose Administration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Assess the Safety, Tolerability and Pharmacokinetics of AZD5634 Following Inhaled and Intravenous (IV)Dose Administration (NCT02679729), a randomized phase 1 study. The primary outcome is Safety and Tolerability of AZD5634 Following Inhaled Administration of Single-ascending Doses (SAD) (Part A) and Following Administration of Single Inhaled and IV Doses (Part B)..

2. Clinical Question

This is an early-phase study designed to characterize a drug in healthy subjects, not a trial testing a clinical outcome in people being treated for cystic fibrosis. The condition listing and the stated healthy-subject population are both present in the registry record; further explanation of the condition listing is not reported in the registry record.

The primary endpoint is broad: it captures participant counts for safety and tolerability across specified periods and study parts. The posted adverse-event figures distinguish serious adverse events from other adverse events for each listed group. They do not, by themselves, provide a single treatment comparison or show the timing, nature, duration or severity of each non-serious event. The registry outcome is recorded as having several categories or time points and is not reduced to one comparison. Accordingly, interpretation should stay descriptive and should not treat these counts as a complete statistical test of safety.

3. Trial Design

The registry describes a Phase I, randomized, single-blind, placebo-controlled study with a parallel model. Its official title divides the study into Part A, single-ascending inhaled doses, and Part B, single inhaled and intravenous doses. The stated purpose was to assess the safety, tolerability and pharmacokinetics of AZD5634 after those administrations. The brief summary characterizes it as a first-in-human single-ascending-dose study in healthy subjects.

Part A included seven inhaled AZD5634 dose groups: 10 µg, 27 µg, 81 µg, 216 µg, 648 µg, 1296 µg and 1692 µg. It also included a placebo group. The arm descriptions say that participants inhaled single doses under fasted conditions and rinsed their mouths with water that was to be swallowed. The recorded rinse volume is described as approximately 100 mL, up to 240 mL. The registry describes these procedures for each Part A dose level.

Part B lists an intravenous AZD5634 dose of 65 µg and an inhaled AZD5634 dose of 1692 µg. Its arm description states that the same subjects received the intravenous dose and, after a washout period of 14 days, received the inhaled dose. Although the registry gives the overall model as parallel, the Part B description identifies within-subject dosing for these administrations. More detail about the relation between the overall model classification and the Part B sequence is not reported in the registry record.

The registry reports enrollment of 63 and study status as completed. The recorded start date is 2016-02-11 and the primary completion date is 2016-10-24. The sponsor is AstraZeneca. The record does not report a sample-size justification or a detailed account of randomization and masking procedures.

The safety outcome population was defined as participants in the safety analysis set who received at least one dose of investigational medicinal product and had any safety data after dosing. The registry's description of that population is the basis for interpreting the posted safety counts; it does not establish that every enrolled participant contributed to every outcome.

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 study consisted of a screening period (Days -28 to -1).

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All partcipants in safety analysis set who received at least 1 dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the 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.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability of AZD5634 Following Inhaled Administration of Single-ascending Doses (SAD) (Part A) and Following Administration of Single Inhaled and IV Doses (Part B)., measured over Screening (serious adverse event, SAE), Day -1 (SAE), Spontaneous plus Predose, 3,12,24, and 48 h postdose (Days 1 to 3), Follow-up 7-10 days postdose, 2 months post final dose..

The primary outcome measures safety and tolerability in terms of the number of participants, covering single-ascending inhaled doses in Part A and single inhaled and intravenous doses in Part B. The registry specifies the safety analysis population as participants who received at least one dose of investigational medicinal product and had safety data available after dosing. It also lists assessment periods spanning screening and Day -1 for serious adverse events, spontaneous reporting and predose assessments, postdose observations on Days 1 to 3, follow-up 7-10 days after dosing, and follow-up 2 months after the final dose.

Participant counts are a direct way to describe how many people in a group had an event recorded. They can be useful for summarizing safety observations in an early-phase study, where the focus includes identifying and characterizing events after exposure. A count alone does not describe the event's clinical details, duration, severity, or whether it was considered related to the study drug. Those details are not reported in the posted serious-event summary.

The registry lists the primary outcome as having several categories or time points and does not reduce it to one comparison. Therefore, it should not be read as a single binary endpoint with one overall effect estimate. The posted adverse-event figures offer group-level counts for serious and other events, while the outcome's broader assessment schedule and the pharmacokinetic measures address different aspects of the study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, single-blind, placebo-controlled Phase I study, but the detailed statistical methods for the primary safety outcome are not reported in the registry record. The outcome is defined in participant counts and spans multiple categories and assessment periods. That structure supports a descriptive reading of the posted counts rather than an assumption that the study tested one prespecified binary contrast.

What does a participant count mean?

A participant count records how many people in a group experienced the type of event being summarized. For safety interpretation, this differs from an event count: one participant can experience more than one event, but a participant-level measure generally counts that person once for the relevant summary. The registry identifies the event measure as participants with an event. It does not give episode counts or event-level records in the adverse-event summary.

Counts should be read alongside the group to which they refer and the safety population definition. The record says participants had to receive at least one dose and have postdose safety data to be included in the safety analysis. A count is not meaningful without that context, since the group size and analysis population determine how much information it represents. Although the posted adverse-event listing includes group sizes at risk, this interpretation does not recalculate percentages or combine groups.

Why are the counts not one overall comparison?

Part A includes multiple inhaled dose levels and placebo, while Part B describes intravenous and inhaled administrations in the same subjects. These groups do not constitute one uniform comparison. In addition, the primary outcome is recorded across categories and time points. A single estimate would require a defined contrast and a rule for combining or selecting outcome periods; such a rule is not reported in the registry record. It would be inappropriate to choose one after seeing the counts and present it as the study's primary analysis.

Randomization can help balance measured and unmeasured characteristics across assigned groups, in expectation, when the design and conduct support that interpretation. The registry identifies the study as randomized, but further details about the allocation procedure and the actual allocation sequence are not reported in the registry record. Single blinding means the record classifies the study as single-blind; who was blinded and how blinding was maintained are not reported in the registry record. These omissions limit how specifically the design features can be assessed.

How should uncertainty be understood?

A confidence interval is a general statistical tool that expresses the uncertainty around an estimate under a specified method. The adverse-event figures are counts, and the registry record does not report confidence intervals or a model-based analysis for them. A zero count is an observed value, not an estimate with no uncertainty. In general, when events are uncommon and group sizes are limited, the absence of observed events can coexist with uncertainty about the underlying event rate.

For event-count outcomes, general statistical methods may need to account for variation beyond what a simple model expects. Over-dispersion is a general term for greater variation in counts than a model assumes, and it can make standard errors too small if ignored. The registry does not report a count model or any assessment of over-dispersion. No model-based conclusion should therefore be attributed to this record.

What does the planning illustration represent?

The posted planning assumptions describe a hypothetical sample-size illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the original trial was designed using those assumptions. The trial's own sample-size justification and design assumptions are not reported in the registry record. The illustration does not replace the need to interpret the actual safety observations, and it should not be treated as a test of the trial's success.

In this study, the primary safety outcome is not reduced to one comparison, and the registry does not provide a specific hypothesis test. Any sample-size calculation based on a selected contrast would be a distinct planning exercise rather than a reconstruction of the study's prespecified analysis. The appropriate statistical reading remains descriptive: identify the population and groups, state the reported counts, and avoid implying precision or causal attribution beyond what the registry reports.

10. Multiplicity, Missing Data and Analysis Populations

The primary safety outcome spans categories and assessment times, and the registry indicates that it is not reduced to one comparison. When an analysis tests several outcomes, groups or time points, multiplicity is a general concern: repeated testing can increase the chance of finding a nominally unusual result by chance. The record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a plan for selecting the primary time point. It is therefore not possible to say how the study handled multiplicity. Since the posted safety results are counts without reported hypothesis tests, no adjusted or unadjusted significance claims should be inferred.

Missing-data handling is also not reported in the registry record. The stated safety population includes participants with at least one dose and any safety data after dosing, but that definition does not explain how missing observations within the listed follow-up periods were treated. It does not establish whether every participant contributed data at every assessment or whether incomplete follow-up was imputed, excluded, or otherwise handled. No assumption about those procedures is warranted.

The outcome population is the safety analysis set, not necessarily every enrolled participant for every analysis. The registry's stated inclusion rule is receipt of at least one dose and availability of postdose safety data. The record does not provide participant-level flow through the safety assessments or clarify the handling of participants who did not meet that rule. Other analysis populations, including any population used for pharmacokinetic analyses, are not fully described in the available record.

These gaps matter because analysis choices can affect the interpretation of event counts and comparisons. The posted numbers can be reported as recorded, but the reader cannot assess sensitivity to missing data, multiplicity procedures, or alternate analysis populations from the registry information.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 column reports 0 affected participants in every listed group: Part A AZD5634 at 10 µg, 27 µg, 81 µg, 216 µg, 648 µg, 1296 µg and 1692 µg; Part A placebo; Part B AZD5634 IV 65 µg; and Part B AZD5634 IN 1692 µg. The registry lists no top serious-event terms. Death counts are not reported in the registry record.

The other adverse-event counts are participant counts, not counts of all event episodes. The counts are 1, 0, 0, 1, 1, 0 and 2 across the Part A AZD5634 groups in ascending dose order; the placebo group has 3. Part B reports 2 for IV 65 µg and 1 for IN 1692 µg. These figures should not be converted into percentages or combined across groups to create a new comparison.

Group-level counts do not tell the reader the event terms, severity, duration, timing, or relationship to study drug. They also do not establish that no events occurred outside the reported safety population or assessment periods. A count of zero means no affected participants were recorded for that category in that listed group; it does not prove the underlying risk is absent. The registry record does not report further event-level detail in this summary.

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

The posted results offer a descriptive account of safety observations across the study's dose groups and placebo group. The registry records no serious adverse events in the listed groups and reports participant counts for other adverse events. That is the scope of the finding: recorded participants in the defined safety analysis, as represented in the registry summary.

The result does not establish that AZD5634 is safe in every population, at every dose, or over every duration. The study is described as Phase I and conducted in healthy subjects, and the recorded administrations were single doses. Its findings should not be treated as evidence about repeated dosing or clinical outcomes in people with cystic fibrosis. The registry lists cystic fibrosis as a condition, but its study summary describes healthy subjects; the relationship between those entries is not reported in the registry record.

The figures do not show that AZD5634 caused the other adverse events, nor do they establish that those events were unrelated. The posted counts do not include the event-level information needed to assess causality, severity, timing or clinical importance. Nor do they provide a comparative estimate with a confidence interval or test. Raw counts across groups with different doses and study procedures cannot support a simple ranking of safety.

The study also included pharmacokinetic outcomes, but outcome names alone are not numerical findings. The listed measures include plasma concentration and exposure summaries, renal clearance, bioavailability and half-life. Without reported values and corresponding analyses, no conclusion can be drawn about exposure, route differences or dose proportionality.

In general, early-phase safety studies contribute information about observations under the conditions studied; they do not rule out uncommon events or settle questions that require different populations, dosing schedules, or follow-up. In this record, the absence of serious adverse events is a finite observation, not proof of zero risk. The defensible interpretation is limited to the posted participant counts and the study characteristics recorded in the registry.

13. Why This Trial Matters Statistically

Statistically, this trial illustrates why outcome structure matters as much as the reported counts. The primary outcome concerns participant numbers across several safety categories and assessment periods, rather than one clearly defined contrast. That makes it important to separate a descriptive summary from an inferential comparison. Without a reported analysis plan, a reader should not assume that one particular category, time point or dose comparison represents the sole primary test.

The design also contains distinct kinds of comparisons. Part A has ascending inhaled doses and placebo, while Part B describes intravenous and inhaled dosing in the same subjects after a washout period. These features raise different interpretive questions: dose-group summaries are not equivalent to randomized comparisons, and within-subject observations differ from comparisons between separate groups. The registry's overall model classification is parallel, while its Part B description specifies the same subjects receiving both routes. The record does not explain this distinction further.

Another important statistical lesson is that zero observed serious events should be stated accurately but not overstated. Zero is a count, not proof that the underlying event probability is zero. Conversely, counts of other events are not evidence of a treatment effect without event details, a suitable comparison and an analysis that accounts for the design. Clear separation of observed data from inference is particularly important when the registry does not report confidence intervals or hypothesis tests.

The study's early-phase purpose combines safety and pharmacokinetic characterization. These are related aspects of drug development but distinct statistical outcomes: adverse-event counts describe observed safety events, while pharmacokinetic measures characterize concentration and exposure. The registry names several pharmacokinetic outcomes, but numerical results are not reported in the registry record. This underscores the need to distinguish the existence of an endpoint from the availability of results for that endpoint.

Finally, planning calculations based on observed effects should not be mistaken for the original design rationale or for observed power. Keeping planning illustrations separate from trial results helps avoid retrospective overconfidence. In this study, the registry's descriptive safety counts are the clearest basis for interpretation; broader conclusions require information 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.

The available registry information does not report event-level descriptions for the other adverse events, including their terms, severity, timing, duration or relationship to AZD5634. It also does not report deaths in the safety summary. These omissions limit clinical interpretation of the participant counts. The serious-event summary lists no event terms, consistent with its zero counts, but this does not supply additional detail about the broader safety record.

The primary safety outcome covers multiple categories and time points, yet is not reduced to one comparison. Statistical analysis methods for this outcome, including any confidence intervals, hypothesis tests or multiplicity procedures, are not reported in the registry record. The handling of missing safety observations and the analysis populations beyond the stated safety-set eligibility description are also not reported.

The registry describes healthy subjects and also lists cystic fibrosis as a condition, without explaining the relation between these entries. The group sizes are small, and the study involves single-dose administrations; therefore, the observations do not establish what may occur in other populations or with other dosing schedules. The overall model is recorded as parallel, while Part B's arm description says the same subjects received IV and inhaled doses after a washout period of 14 days. Further detail reconciling these design descriptions is not reported.

The registry names pharmacokinetic outcomes but numerical results for them are not included in the record information considered in this analysis. The trial's sample-size justification, detailed allocation procedures, blinding implementation and full statistical analysis plan are also not reported in the registry record. As a result, the safety figures support a limited descriptive account rather than a complete evaluation of design conduct, uncertainty or comparative effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: To Assess the Safety, Tolerability and Pharmacokinetics of AZD5634 Following Inhaled and Intravenous (IV)Dose Administration — NCT02679729.
• Registry record last updated 2018-11-05; status last verified 2018-03.
• Results first posted 2018-11-05.
• 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

NCT02679729 is a completed Phase I study sponsored by AstraZeneca. The registry describes a randomized, single-blind, placebo-controlled study of AZD5634 in healthy subjects, with single ascending inhaled doses in Part A and single inhaled and intravenous doses in Part B. Enrollment is reported as 63; the start date is 2016-02-11 and the primary completion date is 2016-10-24.

The primary outcome concerns safety and tolerability measured as participant counts across assessment periods. The posted serious adverse-event counts are 0 in each listed group. Other adverse-event counts are reported by group, but the registry summary does not give event-level detail. The primary outcome is not reduced to one comparison, and inferential methods for it are not reported in the registry record.

Pharmacokinetic outcomes are listed as secondary measures, including concentration, exposure, clearance, bioavailability and half-life. Their numerical results are not reported in the registry record. Interpretation is therefore limited to the available study description and the posted safety counts.