Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes (NCT04556760), a randomized phase 2 study. The primary outcome is Change From Baseline in Glucose Area Under the Plasma Concentration Versus Time Curve From Zero to 4 Hours Post-dose AUC(0-4).

2. Clinical Question

The trial was designed to assess glucose homeostasis in adults with type 2 diabetes. Its primary endpoint focuses on the glucose response after a standardized meal rather than on a single glucose measurement. The record also lists safety, tolerability and pharmacokinetics as study aims, and describes secondary glucose and hormone measures.

The question is organized by cohort and dose, not as one universal comparison. AZD9567 and prednisolone were paired at different dose levels in Cohort 1 and Cohort 2. Cohort 3 instead paired placebo with prednisolone. Those comparisons should be interpreted within their respective cohorts; the registry record does not report a common AZD9567-versus-placebo comparison.

The study description identifies the primary question and endpoint, but does not report the numerical change estimates or a statistical test comparing treatments. Thus, the clinical question can be described from the design, while the magnitude and precision of any observed treatment difference are not reported in the registry record.

3. Trial Design

The registry record describes a Phase 2a randomized, double-blind, multicentre study with a crossover model. It lists an enrollment of 46 and the condition as type 2 diabetes mellitus. The record gives the start date as 2020-11-26, the primary completion date as 2021-06-09, and the status as completed.

In a crossover design, participants receive more than one treatment in sequence, so treatment comparisons can be made using observations from the same participant. This is a general feature of crossover studies, not a statement about the analysis model used in this trial. The record describes two 72 hour treatment periods for each cohort and randomized 1:1 allocation between the two possible treatment sequences. It does not report a washout interval.

Cohort 1 used 72 mg AZD9567 and 40 mg prednisolone. One sequence received AZD9567 followed by prednisolone, and the other received prednisolone followed by AZD9567. Cohort 2 used 40 mg AZD9567 and 20 mg prednisolone in the corresponding sequence arrangements. Cohort 3 compared placebo with 5 mg prednisolone, also in the two possible sequence orders.

The double-blind designation indicates that the study was described as double blind, but the registry record does not specify which roles were masked or how masking was maintained. It also does not report details of the randomization procedure beyond the 1:1 sequence allocation stated for the cohorts.

The primary endpoint was measured on Days -1 (baseline) and Days 4 of Treatment period 1 and 2. The registry identifies the Full Analysis Set as all randomized patients who received at least 1 dose of study treatment. It does not report cohort-specific enrollment or a separate count of participants contributing to each endpoint comparison. Those details should not be inferred from the overall enrollment or from the planned sequence allocation.

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: Patients with type 2 diabetes mellitus who met all the eligibility criteria were randomised in a ratio of 1:1 to a cohort and sequence group. Each cohort was treated for two 72 hour periods in a cross-over design, with a 3-week washout period between treatment periods.

Treatment Period 1 (72 Hours)

Reasons for not completing this period:

Washout Period (3 Weeks)

Treatment Period 2 (72 Hours)

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) consisted of all randomised patients who received at least 1 dose of study treatment.

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: Full Analysis Set (FAS) consisted of all randomised patients who received at least 1 dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Glucose Area Under the Plasma Concentration Versus Time Curve From Zero to 4 Hours Post-dose AUC(0-4), measured over On Days -1 (baseline), and Days 4 (Treatment period 1 and 2).

The primary endpoint is change from baseline in glucose area under the plasma concentration-versus-time curve from zero to 4 hours after dosing, abbreviated AUC(0-4). The unit is minute*millimole/liter (min*mmol/L). The measurement follows a standardized mixed meal tolerance test and is intended to assess the pharmacodynamic effect of AZD9567 compared with prednisolone.

Area under the curve combines measurements across a defined time interval into one summary of the concentration response. As a general statistical concept, this can reflect both the level and duration of a measured response during that interval, rather than relying on a single time point. The endpoint is expressed as change from baseline, so the intended quantity is the difference between a post-baseline assessment and the baseline assessment.

The registry lists baseline measurement on Day -1 and post-dose assessment on Days 4 of Treatment period 1 and 2. It reports least-squares means as the parameter and standard errors as the dispersion measure. A least-squares mean is an adjusted mean from a statistical model in general; however, the registry record does not report the model specification or covariates used for this endpoint. A standard error describes the estimated precision of a mean, but is not itself a confidence interval.

The registry record does not report numerical endpoint estimates, standard errors, confidence intervals or hypothesis-test results. Therefore, the measure and its purpose are identifiable, but the size and precision of the observed treatment responses are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a randomized, double-blind crossover design. Randomization is a method for assigning participants to treatment sequences by chance, which can reduce systematic differences between sequence groups in general. Here, the record states a 1:1 allocation between the two treatment orders in each cohort. It does not describe the sequence-generation procedure, allocation concealment or masking procedures, so those implementation details are not reported in the registry record.

What does crossover mean for the comparison?

In general, a crossover study gives each participant more than one treatment in different periods. A within-participant comparison can reduce the influence of characteristics that remain stable during the study. That advantage depends on design and analysis assumptions. For example, treatment effects should be distinguishable from period effects, and any effect of an earlier treatment should not improperly influence the response in a later period. These are general considerations, not findings about this study.

The registry specifies two 72 hour periods and gives the sequence order for the treatments in each cohort. It does not report a washout interval or explain whether carryover was assessed. It also does not report an analysis model for the crossover structure, including whether period or sequence effects were included. Thus, the presence of a crossover design is clear, but the details of its statistical implementation are not reported in the registry record.

What does the primary measure summarize?

The primary measure is change from baseline in glucose AUC(0-4) after a standardized mixed meal tolerance test. As a general concept, an area under a concentration-time curve summarizes measurements over a specified interval. It can capture the overall response over that interval rather than focusing on one measurement time. A change-from-baseline endpoint expresses the post-baseline response relative to a starting measurement, although the record does not provide the actual values or a calculation-level description of how baseline was incorporated into each analysis.

The endpoint is reported as a least-squares mean with standard error. In general, a least-squares mean is an estimate from a fitted model and may account for terms included in that model. Its interpretation depends on the model specification. A standard error describes sampling uncertainty around an estimated mean; it is not equivalent to a confidence interval and does not alone show the range of plausible treatment effects. The registry does not state the model terms, degrees of freedom, covariance structure or method for constructing any confidence intervals.

How should uncertainty be assessed?

In general, a confidence interval communicates a range of effect values compatible with the data and the chosen method, while a hypothesis test evaluates data compatibility with a specified null hypothesis. Neither can be reconstructed from a least-squares mean alone. The record does not report confidence intervals, test statistics or p-values for the primary endpoint. Consequently, the precision and statistical evidence for a treatment contrast cannot be assessed from the numerical details in the registry record.

There are several treatment pairings across cohorts: two AZD9567 dose comparisons with prednisolone, and a placebo comparison with prednisolone. These are different estimands in general because each involves a different treatment and dose combination. A pooled analysis would require an explicit analytic rationale and method; the record does not report such a rationale or a pooled estimate. No overall contrast should be inferred by combining cohort descriptions.

What does the planning illustration mean?

The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a report of trial power based on the results. The record does not report a sample-size justification for the trial’s own design, and no numerical planning outputs or effect fractions are included in the record details considered for this explanation. Planning illustrations should not be read as observed power or as evidence that an effect was detected.

In general, planning calculations estimate the amount of information needed under specified assumptions. A calculation based on an observed effect is especially dependent on that estimated effect and should not be confused with a prospective design rationale. Here, the registry description labels the calculation as a planning illustration, and the actual numerical endpoint results are not reported in the registry record. Therefore, the planning description cannot fill the gap in the outcome evidence.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 28 outcome measures and 53 analyses. It includes the primary glucose AUC(0-4) change and secondary outcomes covering continuous glucose monitoring, fasting glucose, and changes in insulin, glucagon, GLP-1, GIP and C-peptide. Multiple outcomes or analyses can create a multiplicity issue in general: when many hypotheses are examined, the chance of at least one apparently unusual result can increase unless the analysis plan addresses this.

The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or which analyses were designated as confirmatory. It also does not report an analysis plan that would explain how results across the cohorts, treatment periods, dose levels or outcome measures were to be interpreted together. No particular adjustment or testing strategy should be assumed.

The defined Full Analysis Set consisted of all randomized patients who received at least 1 dose of study treatment. The record does not report additional analysis populations, such as a per-protocol population, or the numbers included in each endpoint analysis. Although the primary endpoint description notes that participants analyzed were kept as 0 in certain treatment rows where a treatment was not administered, those bookkeeping entries should not be interpreted as observed treatment outcomes.

Missing-data procedures are not reported in the registry record. In general, missing observations can affect an estimate if the probability of being missing is related to treatment or outcome, and different assumptions or methods can lead to different results. The record does not describe how missing endpoint values, incomplete treatment periods or withdrawals were handled. It also does not report sensitivity analyses for missing data. These omissions limit assessment of how robust any outcome estimates would be to incomplete observations; numerical primary endpoint estimates themselves are 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 non-serious adverse event terms

The registry lists serious adverse events, other adverse events and deaths by treatment group. For serious adverse events, the affected count is 0 in each listed group: Cohort 1 AZD9567 72mg and prednisolone 40mg; Cohort 2 AZD9567 40mg and prednisolone 20mg; and Cohort 3 placebo and prednisolone 5mg. The deaths count is also 0 in each listed group. No serious adverse event terms are listed.

The other adverse event affected counts are 4 for Cohort 1 AZD9567 72mg, 7 for Cohort 1 prednisolone 40mg, 2 for Cohort 2 AZD9567 40mg, 5 for Cohort 2 prednisolone 20mg, 1 for Cohort 3 placebo and 0 for Cohort 3 prednisolone 5mg. These are reported group counts, not a basis for calculating comparative rates or attributing differences to treatment.

In general, adverse-event counts need context such as event definitions, time at risk, event severity, and whether events were treatment-emergent. The registry record does not report those details here, nor does it provide inferential comparisons for the safety counts. The figures are therefore descriptive, and zero reported serious events should not be treated as proof that serious events cannot occur.

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

The registry record establishes that the study was designed to compare glucose responses after AZD9567 and prednisolone in adults with type 2 diabetes, with a separate placebo and prednisolone comparison in Cohort 3. It identifies a primary measure based on change from baseline in glucose AUC(0-4) after a standardized meal test and describes the assessment timing and reported summary measure.

However, the primary endpoint’s numerical treatment estimates and measures of uncertainty are not reported in the registry record. Without those values, it is not possible to describe the direction, magnitude or precision of the observed treatment differences. The record also does not report hypothesis-test results that would support a statement about statistical evidence for a contrast.

In general, a difference in a measured endpoint is not automatically a complete account of a treatment’s effects. Interpretation depends on the target population, treatment contrast, outcome definition, study design, analysis methods and uncertainty. For this study, the different cohorts use distinct dose pairings, and the registry does not report enough numerical outcome information to compare their responses or combine them into a single conclusion.

The findings should not be extended beyond the study question. The record identifies adults with type 2 diabetes and short treatment periods, but does not report results that establish what the endpoint means for longer-term outcomes or for people outside the described population. It also lists safety, tolerability and pharmacokinetics as aims without providing numerical results for those aims in the record details.

The adverse-event counts are likewise descriptive. They include zero serious adverse events and zero deaths in each listed group, alongside other adverse-event counts. These entries do not establish that risks are absent or that groups differ in safety. More detailed event information and comparative analyses are not reported in the registry record.

Accordingly, the record supports a description of the research question and trial structure, but not a conclusion that AZD9567, prednisolone or placebo produced a particular glucose effect. The completed status indicates that the study is recorded as completed; it does not supply missing estimates or resolve the uncertainty about the primary endpoint.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of a crossover design with several treatment comparisons organized into cohorts. Each sequence places two treatments in opposite orders across two 72 hour periods. In general, such designs can use within-participant comparisons, but interpretation depends on how sequence, period and possible carryover are handled. The registry provides the sequence descriptions but does not report the statistical model used to account for those features.

The study also illustrates why a clearly defined endpoint does not by itself provide evidence about an effect. The primary measure is specified as change from baseline in glucose AUC(0-4), with least-squares means and standard errors identified. Yet the numerical estimates, intervals and tests are not reported in the registry record. Without them, readers cannot assess the size or precision of the response or distinguish a small estimate from a large but uncertain one.

The cohort structure matters for statistical interpretation. AZD9567 and prednisolone are paired at one set of doses in Cohort 1 and another set in Cohort 2, while Cohort 3 compares placebo and prednisolone. These are not identical treatment contrasts. Analyses across several outcomes and comparisons also raise general questions about multiplicity, prespecification and the interpretation of secondary findings. The record does not report how those questions were addressed.

Finally, the safety counts show why descriptive numbers need context. Counts without event timing, exposure details, definitions or comparative analyses cannot provide a complete assessment of treatment-related risk. Overall, the study’s design and endpoints can be described, but meaningful inference requires result estimates and analytic details that 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.

The main limitation for interpreting this trial is that the registry record does not report numerical primary endpoint results. It gives the endpoint definition and summary parameter but not the treatment estimates, standard errors, confidence intervals or p-values. Consequently, neither effect magnitude nor precision can be assessed.

The analysis details for the crossover design are also not reported. The record describes treatment periods and sequence orders, but not the model specification, handling of period or sequence, assessment of carryover, or use of any washout interval. These details matter in general because responses in a crossover study can depend on the order and timing of treatment exposure.

The cohort comparisons involve different doses and different comparator arrangements. The record does not report a single pooled treatment estimate or an analytic rationale for combining cohorts. It also does not provide cohort-specific enrollment or endpoint analysis counts. The overall enrollment should not be used to infer how many participants contributed to any particular comparison.

Missing-data methods, multiplicity procedures, and any hierarchy among outcomes are not reported in the registry record. These omissions make it difficult to assess how incomplete observations or multiple analyses were addressed. Although the record lists numerous secondary measures, numerical results for them are not included in the details.

The safety information is limited to group-level affected counts and deaths or serious-event counts. Event definitions, timing, severity and comparative statistical analyses are not reported. Finally, the record describes the trial as completed, but does not report the sample-size justification for the trial’s own design. A planning illustration based on an observed effect is not a substitute for that justification and is not observed power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes — NCT04556760.
• Registry record last updated 2024-07-18; status last verified 2024-02.
• Results first posted 2024-07-18.
• 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

NCT04556760 is a completed Phase 2a randomized, double-blind, multicentre crossover study in adults with type 2 diabetes. The registry lists enrollment of 46 and describes two 72 hour treatment periods in each cohort. Cohort 1 compared AZD9567 72 mg with prednisolone 40 mg; Cohort 2 compared AZD9567 40 mg with prednisolone 20 mg; Cohort 3 compared placebo with prednisolone 5 mg.

The primary endpoint was change from baseline in glucose AUC(0-4) after a standardized mixed meal tolerance test. It was summarized as a least-squares mean with standard error. The registry record does not report numerical primary endpoint results, confidence intervals or hypothesis-test results. The Full Analysis Set included randomized patients who received at least 1 dose of study treatment. Serious adverse event affected counts and deaths were 0 in each listed group; other adverse-event counts varied by group. Further analytic and missing-data details are not reported in the registry record.