A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 After Single Ascending Doses to Healthy Males: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 After Single Ascending Doses to Healthy Males (NCT02484729), a randomized phase 1 study. The primary outcome is Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events.

2. Clinical Question

This is a safety and tolerability question, not an efficacy question. The study also assessed pharmacokinetics, including measures of drug concentration over time, but the posted primary endpoint is the percentage of participants with adverse events. The registry record therefore supports a description of the observed safety counts and percentages in the listed groups; it does not establish a treatment effect or a definitive comparison between AZD9977 and placebo.

3. Trial Design

The registry classifies this as a Phase I, randomized, single-blind, placebo-controlled study of AZD9977 after single ascending-dose administration to healthy male subjects. It reports a parallel-group model and overall enrollment of 196. AstraZeneca is listed as the sponsor. The study is recorded as completed, with a start date of 2015-07 and primary completion in 2015-11.

The study had distinct parts. Part A is described as including up to 10 cohorts receiving single ascending doses of AZD9977 oral suspension or matching placebo. The posted groups include doses from 5 mg through 1200 mg, including split-dose groups. The Part A results list a separate placebo group and a result for each named AZD9977 group. The posted denominators vary by group.

Part B addressed regional absorption along the gastro-intestinal tract using the IntelliCap system. Its brief description specifies a non-randomized, open-label, fixed-sequence design. AZD9977 oral suspension in an IntelliCap capsule was used, and oral solution was described as a reference. The record does not provide a randomized placebo comparison for Part B. It also does not explain how Part B relates to the randomized and single-blind study-level classifications, so the design features should be read by study part rather than assumed to apply identically to every participant.

The study was conducted at a single study centre, according to the brief summary. The registry record does not report the centre's name, detailed eligibility criteria, dose-escalation decision rules, or the rationale for the overall enrollment target. It also does not report a detailed protocol for allocation concealment or masking beyond the study-level single-blind classification and the Part B description.

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: In this study, 196 subjects were screened out of which 70 subjects were randomized. The study was conducted in two parts (Parts A and B). Part A-eight cohorts of 8 subjects, randomized in 6:2 (AZD9977: placebo) and Part B -1 cohort of 8 subjects who received a single dose of AZD9977, on 2 occasions separated by washout period of 7 days.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects who received at least one 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 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events, measured over For up to 45 days, i.e. from Screening to Follow-up.

The primary endpoint is the percentage of participants with adverse events. It is a binary participant-level measure: a participant is counted according to whether an adverse event was recorded during the specified period. The registry describes the timeframe as up to 45 days, from screening to follow-up, and states that the endpoint was intended to assess the safety and tolerability of single ascending doses of AZD9977.

This kind of endpoint is used in early-phase studies to describe how often participants experience events during or after exposure. Reporting a percentage alongside the number of participants in each group makes the observed frequency interpretable in the context of each group's size. The percentage alone does not describe the event's severity, duration, causal relationship to treatment, or clinical importance. Those details require event-level information and definitions that are not included in the posted primary endpoint results.

The registry defines the safety analysis population as subjects who received at least one dose of investigational medicinal product and for whom any safety post-dose data were available. The endpoint results give a percentage for each listed group, but the record does not provide confidence intervals or an adjusted comparison. The posted endpoint therefore supports descriptive reporting of adverse-event occurrence, not a precise estimate of a causal difference between AZD9977 and placebo.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry posts a participant-level percentage endpoint and separate group denominators. It does not report the statistical method used to calculate the percentages, a comparative model, confidence intervals, or a formal hypothesis test. The interpretation should therefore remain descriptive. The explanations below distinguish general statistical principles from methods actually documented for this study.

What does a participant percentage represent?

In general, a binary endpoint classifies each participant into one of two states for the outcome: the event was recorded, or it was not. A percentage expresses the number of participants with the event relative to the number evaluated in that group. It is useful for describing frequency, but it does not capture how many separate events each participant experienced or how serious those events were. The registry identifies the endpoint as the percentage of participants with adverse events, but does not give a more detailed endpoint definition or event-counting rule.

The listed denominators matter because the same percentage can be more or less stable depending on how many participants contribute to it. In general, smaller groups tend to yield less precise estimates. The posted results do not include confidence intervals, so the uncertainty around each percentage cannot be read directly from the registry. The percentages should not be treated as exact underlying event rates.

What would a confidence interval add?

In general, a confidence interval describes the statistical uncertainty around an estimated quantity under a specified method and assumptions. For a participant percentage, it would give a range of values compatible with the observed data and the interval procedure. A narrow interval would indicate greater precision, while a wide interval would indicate less precision. No confidence interval is reported for the primary endpoint in this registry record, so the reader cannot assess that precision using an interval estimate.

A confidence interval for a difference between groups would address a different question from separate intervals around each group's percentage. It would estimate the range of plausible differences under the analysis method. No such comparison estimate is posted. The group percentages alone do not show whether apparent differences are larger than would be expected from sampling variability.

Why does the design affect interpretation?

In general, random allocation can help make treatment groups comparable on average, while blinding can limit some forms of bias in outcome assessment or reporting. The registry describes Part A as randomized and single-blind, with placebo control. Those design features are relevant to a comparison within Part A, but they do not substitute for a reported analysis. The record does not describe the allocation procedure, the identity of the blinded party, or the handling of deviations from assigned treatment.

Part B is described separately as non-randomized, open-label and fixed-sequence. General principles of comparative analysis caution against treating groups from distinct designs as though they had been assigned under the same process. The Part B result is therefore best read as a separate descriptive safety result, rather than as another randomized comparison with Part A placebo.

What do the analysis and planning records establish?

The registry lists zero analyses. It provides no inferential results for the primary endpoint, including no reported test statistic, p-value, confidence interval, or adjusted treatment contrast. The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The assumptions state that the effect to detect is a specified fraction of the observed effect. Such illustrations are planning calculations, not observed power and not evidence that a particular treatment difference was detected. The record does not report a trial-specific sample-size justification or a comparison for which those illustrations could be interpreted as a study finding.

For general context, over-dispersion is relevant when the variability in data is greater than assumed by a statistical model. If a model does not account for that excess variability, standard errors can be too small and uncertainty can be understated. This concept is not a method reported for this study, and the registry does not provide information that would establish whether over-dispersion was relevant to its analysis.

The primary results are posted as percentages with no associated dispersion measure. The registry does not identify whether a particular interval or model was used, nor does it report covariate adjustment. No statistical method should be attributed to the study beyond the information explicitly recorded. The appropriate reading is therefore to describe the listed group results and avoid inferring unreported tests or precision measures.

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- Placebo", "Part A - 5 mg AZD9977", "Part A - 25 mg AZD9977", "Part A - 100 mg AZD9977", "Part A - 200 mg AZD9977", "Part A - 400 mg AZD9977")
n      <- c(16, 6, 6, 6, 5, 6)
events <- c(7, 1, 2, 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- Placebo  16  7  43.8  19.8  70.1  23.1  66.8  23.0  67.1
ARM  Part A - 5 mg AZD9977  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Part A - 25 mg AZD9977  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  Part A - 100 mg AZD9977  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  Part A - 200 mg AZD9977  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1
ARM  Part A - 400 mg AZD9977  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 10 posted secondary outcomes, including pharmacokinetic measures such as area under the concentration-time curve, maximum observed concentration, time to maximum concentration, terminal half-life, apparent clearance, apparent volume of distribution, and the cumulative amount of unchanged drug excreted into urine. The primary endpoint concerns adverse events; these secondary outcomes address drug exposure and disposition rather than the same safety question.

When a study evaluates multiple outcomes or makes multiple comparisons, general statistical practice considers whether the analysis plan controls the chance of false-positive findings across those tests. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a plan distinguishing confirmatory from exploratory analyses. It also lists zero analyses, so no posted inferential results are available to assess for multiplicity.

Missing-data handling is not reported in the registry record. The primary safety population is defined by receipt of at least one dose and availability of any post-dose safety data. That definition identifies who was eligible for the safety analysis, but does not explain how missing endpoint information was handled, whether any participants lacked follow-up, or whether exclusions occurred after enrollment.

The registry reports overall enrollment of 196 and gives group-specific denominators for the primary endpoint. It does not reconcile the overall enrollment with those listed groups or explain the contribution of participants to each analysis group. It also does not report imputation procedures, sensitivity analyses, or reasons for missing data. Consequently, the posted percentages can be described for their stated groups, but the completeness of outcome ascertainment and the influence of missing data cannot be evaluated from this record.

12. 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 summary reports zero affected participants in each listed group: Part A placebo, every listed Part A AZD9977 dose group, and Part B. The number at risk is also reported for each group. These figures are counts of participants with serious adverse events, not counts of all adverse events and not a formal comparison between groups.

Zero reported serious adverse events in a group means that none were recorded among the participants included in that group during the reported safety assessment. It does not establish that the true risk is zero or rule out events that might occur in a larger population or different setting. The listed groups are small, and the registry does not provide confidence intervals or a statistical analysis of serious-event risk.

The death counts are not reported in the registry record. The record also does not provide serious-event terms in the posted summary, so the nature of any events cannot be described. The separate other-adverse-event counts should not be confused with serious adverse events, and neither category by itself establishes that an event was caused by AZD9977. Causal attribution and event-level details are not reported in the registry record.

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

The posted results show that adverse events were reported in each listed group except the Part A 800 mg AZD9977 group, for which the registry reports 0.0%. The highest listed percentage is 43.8% in Part A placebo, and other group percentages range from 16.7% to 37.5%. Those figures describe the observed participant percentages for the listed groups, during the registry's specified safety period of up to 45 days from screening to follow-up.

These results do not demonstrate that AZD9977 reduces, increases, or has no effect on adverse-event risk relative to placebo. The group sizes are limited, the design differs for Part B, and the registry provides no confidence intervals or inferential comparisons. Differences among percentages can reflect uncertainty as well as any underlying differences between groups. The record does not report causal attribution for the adverse events, so the observed events cannot be assumed to have been caused by the study treatment.

The zero serious adverse events reported in the listed groups is also a descriptive result, not a guarantee of safety. It is limited to the participants, doses, and observation period recorded in the registry. The record does not report deaths, detailed event terms, or the longer-term experience beyond the stated follow-up period.

The study was designed to assess safety, tolerability and pharmacokinetics after single doses in healthy male participants. Its results should not be extended to repeated dosing, other populations, or outcomes that were not reported. The registry also does not provide enough information to assess the precision of the pharmacokinetic outcomes or the detailed statistical handling of missing observations. The appropriate conclusion is confined to the descriptive safety findings and the limits of their reporting.

14. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early-phase research: a trial can report percentages for multiple dose groups while offering limited information about the precision of those estimates. Here, the primary endpoint results are presented as participant percentages with group denominators, but without confidence intervals or inferential comparisons. That makes clear reporting of the underlying group sizes especially important.

The varied percentages across the listed dose groups also illustrate why descriptive results should not be mistaken for a dose-response conclusion. The observed pattern is not a simple stepwise progression, and the group sizes are small. Without a prespecified analysis and uncertainty estimates, apparent differences should be treated as observations rather than evidence of a statistically established contrast.

The study also includes distinct design features across its parts. Part A is described as randomized, single-blind and placebo-controlled, while Part B is non-randomized, open-label and fixed-sequence. Recognizing that distinction is essential: results from different design structures cannot automatically be combined into a single comparative interpretation.

Finally, the record separates a safety endpoint from pharmacokinetic outcomes and reports multiple secondary outcomes. Because the registry does not document a multiplicity strategy, missing-data methods, or inferential analyses, readers should distinguish the outcomes that were registered from the analyses that were actually reported. The case demonstrates the value of registry records for understanding study intent and observed results, while also showing the limits of interpreting those results when statistical detail is absent.

15. Limitations

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

The registry record supplies descriptive safety results but little detail about the statistical analysis. It does not report confidence intervals, hypothesis tests, adjusted comparisons, or the method used to calculate uncertainty. This limits assessment of the precision of the primary endpoint percentages and prevents a formal comparison of the AZD9977 groups with placebo.

The listed primary endpoint denominators are small and differ by group. Overall enrollment is recorded as 196, but the record does not explain how that total relates to the group denominators shown for the primary endpoint. The analysis population is defined in general terms, but the record does not report participant flow, the number with missing safety data, or reasons for any exclusions.

The study's parts also differ in design. Part B is described as non-randomized, open-label and fixed-sequence, whereas the study is otherwise classified as randomized and single-blind. The record does not provide enough detail to resolve how study-level design descriptors apply across parts. The Part B result should therefore not be assumed to have the same comparability as the Part A results.

Further safety limitations include the absence of event-level descriptions, causal attribution, and reported death counts. Although the serious adverse-event summary reports zero affected participants in each listed group, the registry does not provide interval estimates or longer-term follow-up beyond the stated timeframe. The record also does not report the sample-size rationale, interim analyses, detailed dose-escalation rules, multiplicity procedures, or missing-data methods. These omissions constrain interpretation and should not be filled by assumptions about the protocol.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 After Single Ascending Doses to Healthy Males — NCT02484729.
• Registry record last updated 2017-04-28; status last verified 2017-03.
• Results first posted 2017-03-24.
• 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

NCT02484729 is a completed Phase I study sponsored by AstraZeneca. The registry describes a randomized, single-blind, placebo-controlled study of single ascending doses of AZD9977 in healthy male subjects, with Part B separately described as a non-randomized, open-label, fixed-sequence assessment of regional absorption. Overall enrollment is 196.

The primary endpoint was the percentage of participants with adverse events over up to 45 days from screening to follow-up. Posted percentages vary across the listed placebo and AZD9977 groups. The serious adverse-event summary reports zero affected participants in each group, while death counts are not reported in the registry record.

The record provides no inferential analyses or confidence intervals for the primary endpoint. It also does not report a detailed statistical plan, multiplicity procedures, or missing-data methods. The posted results should therefore be read as descriptive findings for the stated groups and timeframe.