A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5718 After Single and Multiple Ascending Dose Administration to Healthy Male Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5718 After Single and Multiple Ascending Dose Administration to Healthy Male Subjects (NCT02632526), a randomized phase 1 study. The primary outcome is Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B)..

2. Clinical Question

The study asked whether AZD5718 could be administered to healthy male subjects in single-dose and multiple-dose regimens while monitoring safety, tolerability, pharmacokinetics and pharmacodynamics. Its primary outcome focused on participants with adverse events after oral dosing. The design also included placebo groups and more than one formulation, making the clinical question broader than a single drug-versus-placebo contrast.

This is an early-phase safety and pharmacology question, not a trial of clinical benefit in people with cardiovascular disease. The registry record describes healthy subjects and provides no patient-outcome results. The adverse-event counts can describe what was recorded in the listed groups, while the listed pharmacokinetic outcomes indicate that absorption was also assessed. The record does not report results for those pharmacokinetic outcomes or a specific pharmacodynamic result.

3. Trial Design

The registry identifies this as a Phase I, randomized, single-blind, placebo-controlled, parallel study. It describes two parts: Part A, a single ascending dose study, and Part B, a multiple ascending dose study. Enrollment was 96. The record lists a start date of 2016-02-10 and a primary completion date of 2016-08-26, and its status is completed.

Part A included amorphous AZD5718 doses of 25 mg, 50 mg, 100 mg, 300 mg, 600 mg and 1200 mg, plus placebo. It also included crystalline suspension at 100 mg and 300 mg, plus a separate placebo group. Part B included amorphous AZD5718 at 60 mg, 180 mg, 360 mg and 600 mg, plus placebo. The registry describes Part B dosing as repeated administration, with dosing schedules that varied across arm descriptions.

The record describes the study as randomized and single-blind, but does not report further details about the randomization sequence, allocation concealment or who was blinded. Although it is a parallel study, the registry’s multiple doses, formulations and parts mean that the posted groups should not be treated as one simple two-arm experiment. The record does not report a single allocation ratio for the study as a whole.

These design features support an early-stage assessment of tolerability and exposure across dose levels and formulations. Placebo groups provide a context for interpreting adverse events, while the crystalline and amorphous formulations permit formulation-specific assessment. The registry record does not give a protocol rationale for the selected doses, explain how escalation decisions were made, or describe whether dose groups were enrolled sequentially. The arm descriptions include some schedule details, but do not provide a complete operational account of conduct.

The study’s healthy-subject population and early-phase structure limit what can be inferred about outcomes in patients. The registry record describes safety, tolerability, pharmacokinetic and pharmacodynamic objectives, but its posted results summarized in the record are adverse-event counts. Results for drug concentrations, pharmacodynamic measures and formal comparisons are not reported in the registry record.

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: Screening period was from Day -28 and Day -1. Participants signed informed consent form; demographic data, medical history and concomitant medication details were collected; weight, height and body mass index were measured; inclusion/exclusion criteria were checked, serology and screening of urinary drugs of abuse, alcohol and cotinine were done

Overall Study

Analysis population for the primary outcome, as defined in the registry: All randomized subjects 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 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B)., measured over From screening to last followup visit (7-10 days after last dose), up to 6 weeks (Part A) and up to 8 weeks (Part B).

The primary endpoint counts participants with adverse events after oral administration of AZD5718 in Part A and Part B. The registry defines the safety analysis population as randomized subjects who received at least one dose of investigational medicinal product and had any post-dose safety data available. The stated observation window ran from screening to the last follow-up visit, described as 7-10 days after the last dose, and lasted up to 6 weeks in Part A and up to 8 weeks in Part B.

In general, adverse-event monitoring is used in early-phase studies to describe tolerability and identify potential safety concerns during and after exposure. Counting participants with events is a simple summary, but it does not by itself convey event severity, duration, recurrence or clinical importance. It also does not establish that an event was caused by study treatment. Those interpretations require details about event definitions, attribution and the individual event records; such details are not reported in the registry record presented for this outcome.

The primary outcome is a participant count rather than a continuous measurement. The posted results distinguish serious adverse events from other adverse events, and present counts by dose, formulation and study part. The registry record does not provide a single summary contrast or an inferential estimate for the primary outcome. As a result, the group counts are descriptive: they show what was recorded in each group, without establishing a comparative treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: an adverse-event count is a binary outcome at the participant level when the measure is whether a participant experienced an event. Each participant is classified as having or not having the specified event during the stated observation period. This kind of summary is useful for showing how many people in a group were affected, but it compresses potentially important information. It does not describe how many events occurred in an affected participant or how severe, persistent or medically important the events were.

What does a group count tell us?

A count should be interpreted alongside the number of participants at risk in the same group. The registry results report those group-specific denominators for serious and other adverse events. Keeping the group and outcome paired avoids confusing counts across different doses, formulations or study parts. Because this study contains several groups, the counts are not a single comparison between AZD5718 and placebo.

General statistical explanation: a confidence interval describes the range of values compatible with the data under a specified statistical method. For a participant-level event outcome, an interval around a proportion or a contrast can express sampling uncertainty. The registry record does not report confidence intervals for the adverse-event outcome. Consequently, readers cannot use the record to assess the precision of a formal group difference from an interval estimate.

Why are comparisons difficult to summarize?

The primary outcome is reported across multiple categories: Part A and Part B, several doses, two formulations in Part A, and placebo groups. The record explicitly indicates that the primary outcome has several categories or time points and is not reduced to one comparison. That means there is no single primary contrast in the posted results to interpret as a treatment effect. A numerical comparison selected after the fact would not replace the sponsor’s prespecified analysis, and the registry record does not report the details of such a plan.

General statistical explanation: when many groups or outcomes are examined, the chance of a seemingly unusual result can increase if each is assessed separately without accounting for multiplicity. Multiplicity procedures can control error rates or otherwise define how a family of comparisons is interpreted. The registry record does not report a multiplicity strategy for the primary or secondary outcomes, nor does it establish which comparisons were confirmatory. Therefore, no multiplicity-adjusted conclusion can be drawn from the posted counts.

What does the planning illustration mean?

General statistical explanation: a sample-size planning illustration asks how many participants per arm might be needed under specified assumptions to detect a target effect with a chosen power. It is not a measure of the probability that a completed study’s result is correct, and it is not observed power. The planning assumptions described for this study use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The registry record says that time-to-event illustrations, when applicable, use total events, while other illustrations use participants per arm.

Those assumptions are planning illustrations, not a description of the original trial’s design justification. The registry record does not report the trial’s own sample-size justification. Since the primary outcome is presented across several groups rather than as one comparison, a planning result for a chosen contrast would depend on that contrast and the assumed effect. It should not be read as evidence that the completed study had adequate power for every dose, formulation or outcome.

General statistical explanation: over-dispersion matters when the observed variability in data exceeds what a chosen model expects. In count outcomes, this can make standard errors too small if a model assumes less variability than the data contain. The primary safety outcome is a count of participants with an event, rather than a recurrent-event count model in the registry description. The record does not report an over-dispersion assessment or a modeling approach, so there is no basis to infer that such a method was used.

What can be inferred from the posted analysis?

The record provides group-level adverse-event counts and identifies a safety analysis population. It does not report a formal test, a model specification, adjusted estimates, confidence intervals or a complete statistical analysis plan. The record lists 30 outcome measures and 10 analyses, but those counts alone do not identify which analysis generated a particular result or how multiple results were handled. No recalculated estimate should be substituted for the sponsor’s analysis when the formal result is not reported.

General statistical explanation: in randomized trials, the target analysis population matters because exclusions after randomization can affect comparability. The safety population includes randomized subjects with at least one dose and available post-dose safety data. The registry does not report whether additional exclusions occurred, how missing safety information was handled, or how this population relates to every randomized participant. The stated population definition therefore helps interpret the safety counts, but does not answer all questions about analysis-set construction.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures and 10 analyses. The primary outcome itself is represented across several categories and time points and is not reduced to one comparison. Secondary outcomes include multiple pharmacokinetic measures, including area under the concentration curve, maximum plasma concentration and time to maximum concentration, across study parts and formulations. With many outcomes and groups, the interpretation depends on which comparisons were planned and how multiplicity was addressed.

The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or which analyses were intended to be confirmatory. It also does not report a complete statistical analysis plan or interim-analysis procedures. Those details should not be inferred from the fact that the study was randomized or that a list of outcomes is available. Formal comparisons and adjusted estimates are not reported in the registry record.

The safety analysis population is described as randomized subjects who received at least one dose and had post-dose safety data available. The record does not report how missing outcome data were handled, whether any participants were excluded after randomization, or the extent of missingness by group. It also does not provide enough information to determine whether all randomized participants contributed to each outcome analysis. These omissions matter because analysis populations and missing-data methods influence how results should be interpreted.

For the adverse-event counts, the record provides group-level denominators and counts, but not a missing-data analysis or sensitivity analysis. The available information supports descriptive reading of those reported groups; it does not support claims about the robustness of a comparative estimate.

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 non-serious adverse event terms

The serious adverse-event results report zero affected participants in every listed dose and placebo group. The death count is zero in each listed group as well. These findings describe the registry record’s observed counts during the stated safety follow-up; they do not establish that the underlying risk is zero or that a future study would observe the same pattern.

For other adverse events, the posted counts are participants affected, not the total number of events. In Part A, the amorphous-dose groups report counts of 0 to 4 across the listed doses; the crystalline-dose groups report 0 and 2, and crystalline placebo reports 1. In Part B, the amorphous-dose groups report 2 or 3, while placebo reports 4. The counts should be read within their own groups and study parts, not combined into a single study-wide value.

General statistical explanation: when no serious events are observed in a group, the data still allow uncertainty about how often such events could occur. The registry record does not report precision intervals for these counts. It also does not report event-level descriptions, severity distributions or attribution details in the results presented, so the counts alone cannot characterize the clinical nature of the reported events.

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

The registry results describe reported participant counts for serious and other adverse events across dose, formulation and study-part groups. No serious adverse-event participants or deaths are reported in the listed groups. Other adverse-event counts vary across those groups. This is useful descriptive information for an early-phase study, where safety and tolerability are central objectives.

These results do not establish a comparative safety effect. The registry record does not report a single primary contrast, an inferential test, confidence intervals or adjusted estimates. The group counts do not show whether observed differences are compatible with chance variation, and they do not justify selecting one dose or formulation as safer than another. A zero count in a group is not proof that the event cannot occur.

The results also do not establish pharmacokinetic or pharmacodynamic effects. The registry lists measures of absorption, but results for those measures are not reported in the registry record. No specific pharmacodynamic result is reported. The listed study objectives therefore should not be mistaken for evidence that those outcomes were observed or that a particular exposure pattern was demonstrated.

The study description concerns healthy male subjects in a Phase I setting. It does not provide evidence about treatment outcomes in people with cardiovascular disease, despite that condition appearing in the registry record. Nor do the posted counts establish long-term safety: the specified follow-up was limited to the stated study windows, and the record does not report longer-term outcome data.

In general, an early-phase study can characterize the observations made under its dose and monitoring conditions, but broader conclusions depend on the design, sample size, precision and complete analysis results. Here, the registry supports a cautious account of the adverse-event counts. It does not support a claim that AZD5718 works or does not work, or that the recorded pattern predicts outcomes outside the studied setting.

13. Why This Trial Matters Statistically

This trial illustrates why early-phase safety results need to be interpreted at the level at which they were collected. The study includes multiple doses, two oral suspension formulations in Part A, placebo groups, and distinct single-dose and multiple-dose parts. Each group provides a separate descriptive context. Treating all groups as one comparison would obscure the design and could imply a contrast that the registry record does not report.

It also illustrates the difference between a count and an estimate of a treatment effect. The adverse-event counts communicate how many participants were recorded with events in each group. Without a reported comparative estimate and its uncertainty, they cannot show whether differences between groups are more than expected from sampling variability. General statistical explanation: precision is especially important when event counts are small, because limited observations can leave substantial uncertainty even when no event is recorded.

The registry lists pharmacokinetic outcomes alongside safety outcomes, but the presence of an outcome in a registry does not supply its result. Separating stated objectives from reported results is essential when interpreting a trial record. Similarly, a planning illustration based on an observed effect is not observed power and does not establish that the original design was planned around that effect.

Finally, the record makes analysis-population and multiplicity questions visible. It defines a safety population, yet does not report all details about missing data or the statistical plan. With many outcomes and groups, those omissions limit how far descriptive results can be taken toward confirmatory conclusions. The appropriate statistical reading is therefore precise but restrained: describe the posted counts, preserve the group distinctions, and avoid claims that require unreported analyses.

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 posted results are limited to group-level adverse-event counts. The registry record does not report event-level descriptions, severity, duration, recurrence or attribution in the results presented. As a result, the counts cannot characterize the nature of the events or establish whether they were related to treatment.

The study includes several dose groups, formulations and parts, but the primary outcome is not reduced to a single comparison. Formal comparative estimates, confidence intervals, statistical tests and adjustment methods are not reported in the registry record. The record also does not report a multiplicity plan, complete statistical analysis plan, interim analyses, or the original sample-size justification.

Although the safety population is defined, missing-data handling and the relationship between enrollment and analyzed participants are not fully described. The registry record does not report sensitivity analyses or enough detail to assess the impact of missing safety information. Results for the listed pharmacokinetic measures and specific pharmacodynamic findings are also not reported.

General statistical explanation: small group counts can be imprecise, and a zero count does not establish absence of risk. The record does not provide precision intervals to quantify that uncertainty. The healthy male subject population, limited follow-up windows and Phase I setting also restrict how the findings can be generalized. The registry lists cardiovascular disease as a condition, but the study description identifies healthy male subjects and provides no patient-outcome results for people with cardiovascular disease.

These limitations do not invalidate the descriptive counts. They define what those counts can support: a record of observed group-specific events under the study conditions, rather than a complete comparative safety assessment or evidence about clinical benefit.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5718 After Single and Multiple Ascending Dose Administration to Healthy Male Subjects — NCT02632526.
• Registry record last updated 2019-03-21; status last verified 2018-12.
• Results first posted 2019-03-21.
• 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

NCT02632526 is a completed Phase I randomized, single-blind, placebo-controlled, parallel study of AZD5718 in healthy male subjects. It had two parts: single ascending doses in Part A and multiple ascending doses in Part B. Enrollment was 96, with a start date of 2016-02-10 and primary completion date of 2016-08-26.

The primary outcome was the number of participants with adverse events. The posted results report zero participants with serious adverse events and zero deaths in each listed group, alongside group-specific counts for other adverse events. The registry record does not report a single comparative estimate for the primary outcome. Pharmacokinetic outcomes are listed, but their results and specific pharmacodynamic results are not reported in the registry record.