Safety and Tolerability Study of MEDI0382 in Japanese Preobese or Obese Subjects With Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability Study of MEDI0382 in Japanese Preobese or Obese Subjects With Type 2 Diabetes (NCT03645421), a randomized phase 2 study. The primary outcome is Mean Change From Baseline in 24-Hour Heart Rate at Days 20 and 48.

2. Clinical Question

The clinical question is about a measured physiological outcome during a short treatment period, not a direct measure of glycemic control. HbA1c, fasting plasma glucose, fructosamine, time in hyperglycaemia or hypoglycaemia, and MEDI0382 trough concentration are listed as secondary outcomes. Their presence indicates additional areas of assessment, but does not establish what the results were. The posted record does not state a single numerical estimate of the primary treatment contrast, its uncertainty, or a test of that contrast. Accordingly, the registry description supports identifying what the investigators planned to measure, but not determining the size or precision of any difference in heart-rate change.

3. Trial Design

This was a Phase IIa, randomized, parallel, double-blind, placebo-controlled study of MEDI0382 in Japanese preobese or obese participants with type 2 diabetes and inadequate glycemic control with diet and exercise. The registry reports enrollment of 61 and a completed trial. The recorded start date is 2018-08-10 and the primary completion date is 2019-01-17.

The treatment arms represented escalating target doses of 100, 200 or 300 µg/day, alongside placebo. For the 100 µg regimen, the description specifies 50 µg/day for the first 5 days, followed by 100 µg/day for 43 days. For the 200 µg regimen, it specifies 50 µg/day for the first 5 days, 100 µg/day for 7 days, and 200 µg/day for 36 days. For the 300 µg regimen, it specifies 50 µg/day for the first 5 days, 100 µg/day for 7 days, 200 µg/day for 7 days, and 300 µg/day for 29 days. Each regimen was administered by subcutaneous injection. The placebo description states one injection per day on 48 days.

The parallel design means participants were assigned to a treatment group rather than described as switching between treatments. Randomization and double masking are recorded, but the randomization method, allocation concealment procedures, and who was masked are not reported in the registry record. The registry characterizes the study as designed to assess safety and tolerability, as well as efficacy and pharmacokinetics. Its primary outcome is mean change from baseline in 24-hour heart rate at Days 20 and 48. The record does not report the planned allocation ratio, a sample-size justification, or a detailed statistical analysis plan.

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 an early stage of T2DM who had inadequate blood glucose control, defined as glycated haemoglobin (HbA1c) between 7.0% and 10.5%, and who were treated with diet and exercise were enrolled. A body mass index of 24 to 40 kg/m2 was also a requirement. Patients with acutely decompensated blood glucose control were excluded.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set included all randomised patients who received at least 1 dose of IP, analysed according to the treatment received. Patients with data available at each timepoint are presented.

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: Baseline characteristics are presented for the Full Analysis Set which included all randomised patients who received at least 1 dose of IP, analysed according to their randomised treatment group.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in 24-Hour Heart Rate at Days 20 and 48, measured over Baseline (Day -1) and Days 20 and 48..

The primary endpoint is mean change from baseline in 24-hour heart rate, measured in beats per minute at Days 20 and 48. Heart rate was assessed using an ambulatory blood pressure monitoring device. The baseline reference is Day -1. The endpoint therefore describes how the average 24-hour heart rate at each follow-up timepoint differs from the participant’s baseline measurement.

A mean change is a summary of a continuous outcome. It can describe the direction and average magnitude of change within a treatment group, while a comparison between groups can estimate whether the average change differs between assigned treatments. The registry lists standard deviation as the measure of dispersion, which describes how variable individual measurements are around the group mean. The mean and standard deviation answer different questions: the mean locates the group average, while the standard deviation describes spread among observations.

Heart rate is the primary outcome in this trial, while glycemic measures and pharmacokinetic outcomes are listed as secondary outcomes. The primary measure can characterize a physiological response during treatment, but its interpretation depends on the reported estimate, its uncertainty, and the comparison being made. Those numerical primary outcome results are not reported in the registry record. The description alone therefore establishes what was measured and when, not the observed direction, size, or precision of the change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-blind, parallel-group design. In general, random allocation is intended to reduce systematic differences between treatment groups at the start of a study, while masking is intended to limit changes in participant or study-team behaviour that could influence measurement or reporting. The registry records those design features, but does not describe the sequence-generation method, allocation concealment, or the exact masking procedures. Those details are not reported in the registry record.

What does a mean change estimate?

The primary outcome is a continuous measure: mean change from baseline in 24-hour heart rate. A continuous outcome can take a range of numerical values rather than representing a yes-or-no event. For each follow-up timepoint, a mean change summarizes the average difference between follow-up and baseline measurements among participants with data available at that timepoint. A group mean describes its average response; a between-group contrast is needed to estimate how average responses differ between treatment groups. The registry defines the endpoint but does not report the values needed to interpret either summary.

The registry identifies standard deviation as the dispersion measure. In general, standard deviation describes how spread out individual observations are around the mean. It is not the same as the standard error, which describes the precision of an estimated mean, and it is not a confidence interval. The posted record does not give the endpoint’s numerical standard deviations or confidence intervals. Thus, the variability and precision of the primary estimates cannot be assessed from the registry entry.

Why does the analysis population matter?

The primary endpoint population is described as the Safety Analysis Set. It includes randomized patients who received at least one dose of investigational product, and participants are analysed according to the treatment received. This definition differs from an intention-to-treat approach that analyses participants according to randomized assignment, regardless of treatment received. The registry does not state that an intention-to-treat analysis was used for this endpoint. It also says that patients with data available at each timepoint are presented, so the contributing set of participants can vary by timepoint if measurements are missing. The number and reasons for missing primary endpoint observations, and the method used to handle missing data, are not reported in the registry record.

In general, analysing available observations can be straightforward, but it may create bias if the likelihood of having a measurement is associated with the outcome or treatment. Methods such as imputation or model-based approaches can address missingness under specified assumptions, but no such method is described in this record. Without the missing-data pattern and analysis method, readers cannot evaluate how sensitive the estimates might be to unavailable measurements.

How should multiple outcomes and timepoints be considered?

The primary measure is assessed at Days 20 and 48, and multiple secondary outcomes are also listed. Testing several outcomes or timepoints can increase the chance of finding an apparently unusual result when each is assessed separately. In general, a prespecified multiplicity strategy can control the overall error rate, or analyses can be interpreted as exploratory when no adjustment is planned. The record lists 15 outcome measures and 15 analyses, but a multiplicity procedure or hierarchy for interpreting them is not reported in the registry record. The record also indicates that the primary outcome has several categories or timepoints and is not reduced to one comparison. It is therefore not possible to identify a single primary contrast or determine how multiplicity was handled.

What can planning calculations tell us?

In general, a sample-size calculation estimates how many participants a future study may need under stated assumptions about variability, effect size, allocation, and significance level. The registry’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe planning for an effect expressed as a fraction of the observed effect. Such calculations are planning illustrations, not observed power and not proof that the original trial was designed around those assumptions. The trial’s own sample-size justification and detailed analysis plan are not reported in the registry record.

Planning calculations based on an observed effect can be especially sensitive to uncertainty in that effect. In general, a noisy estimate may not provide a stable basis for planning a later study, so illustrations at different fractions of an observed effect can show how assumptions influence a planning estimate. This does not add evidence about what occurred in the completed trial. The registry entry does not give numerical primary outcome estimates, and the numerical planning results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 15 analyses. The primary endpoint has measurements at Days 20 and 48, and the listed secondary outcomes cover glycemic measures, time in hyperglycaemia and hypoglycaemia, and pharmacokinetic concentration. The record states that the primary outcome has several categories or timepoints and is not reduced to one comparison. A multiplicity adjustment, endpoint hierarchy, or other plan for interpreting results across outcomes and timepoints is not reported in the registry record.

In general, multiplicity matters because interpreting many separate statistical tests as if each were the only test can increase the chance of false-positive findings. A prespecified strategy can define which outcomes are confirmatory and how evidence is assessed across them. Without that strategy, individual results may need cautious interpretation, particularly when outcomes or timepoints are considered separately. The registry does not provide enough information to determine whether any adjustment was used.

The primary endpoint population is the Safety Analysis Set: randomized participants who received at least one dose of investigational product, analysed according to treatment received. The registry further states that participants with data available at each timepoint are presented. It does not report the number of missing primary endpoint measurements, reasons for missingness, or procedures for handling missing data. It also does not report whether the analysis used imputation, a repeated-measures model, or another method. These absences limit assessment of how participant availability could affect the reported estimates.

The randomized design and stated analysis population are relevant when judging how closely the analysis preserves the original group assignment. However, the record does not describe a separate intention-to-treat analysis. A sample-size justification, interim-analysis plan, and detailed statistical analysis plan are not reported in the registry record. The stated planning assumptions do not establish that those assumptions governed the original study.

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 four groups for adverse-event reporting: placebo and MEDI0382 100, 200 and 300 mcg. In each listed group, the serious adverse event count is zero; the corresponding at-risk counts are 16 for placebo and 15 for each MEDI0382 dose group. Deaths are recorded as zero in every group. These are the counts reported in the registry record and should be read as descriptive safety data for the listed groups.

For other adverse events, the registry reports affected counts of 6 in placebo, 6 in the 100 mcg group, 11 in the 200 mcg group, and 9 in the 300 mcg group. The at-risk counts for these entries are 16, 15, 15 and 15, respectively. The record does not provide event-specific terms in the registry record for this summary, nor does it report severity, timing, duration, treatment relatedness, or a statistical comparison between groups. The registry lists no top serious-event terms.

In general, a count of affected participants is not the same as a count of every event, because a participant may experience more than one event. The registry’s summary counts alone also do not establish whether observed differences between groups are meaningful or attributable to treatment. Absence of recorded serious events in these entries is not a guarantee that no risk exists beyond the period and observations represented in the registry record.

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

The record supports a description of the trial’s design and planned outcome assessment. It was a randomized, double-blind, parallel, placebo-controlled Phase IIa study in Japanese preobese or obese participants with type 2 diabetes. MEDI0382 was escalated from 50 µg/day toward target doses of 100, 200 or 300 µg/day, and the primary outcome was mean change from baseline in 24-hour heart rate at Days 20 and 48.

It does not support a numerical conclusion about the primary endpoint. The registry record does not report the mean changes, standard deviations, confidence intervals, p-values, or treatment contrasts. Without those results, readers cannot determine the observed direction or size of any difference, or how precisely it was estimated. The listed secondary outcomes likewise identify what was assessed, but do not establish results for those outcomes.

The adverse-event record reports no serious adverse events and no deaths in the listed groups, while reporting other adverse events in each group. Those entries are descriptive and do not include event-level details or a statistical comparison. They cannot, by themselves, establish that treatment is safe or unsafe, or determine whether any event was caused by a study treatment.

In general, a clinical trial result needs to be read in light of its estimate, uncertainty, outcome definition, analysis population, missing-data handling, and multiplicity approach. The registry does not report several of those details for this endpoint. The appropriate conclusion is therefore limited: the record describes a completed study and its assessment framework, but it does not provide enough numerical primary outcome information to quantify the observed treatment response or its precision. No claim about treatment benefit or lack of benefit follows from the endpoint description alone.

13. Why This Trial Matters Statistically

This study is statistically notable for placing a physiological primary endpoint alongside a dose-escalation design and multiple secondary outcome domains. The primary endpoint measures mean change in 24-hour heart rate at Days 20 and 48, while the listed secondary outcomes include glycemic measures, time spent in hyperglycaemia or hypoglycaemia, and drug concentration. This illustrates why a registry record should be read as both a description of the research question and a source of information about what outcomes were planned.

The primary endpoint is a continuous measure, and its interpretation depends on more than the group mean. The variability around the mean, the between-group contrast, and the uncertainty of that contrast all matter. The registry identifies standard deviation as the dispersion measure and defines the Safety Analysis Set, but the numerical endpoint results are not reported in the registry record. The absence of estimates prevents a statistical reading of effect size and precision, despite the availability of a detailed endpoint definition.

The design also makes analysis choices important. The primary outcome spans multiple timepoints, the registry lists multiple outcome measures and analyses, and patients with available data are presented at each timepoint. A multiplicity strategy and missing-data approach are not reported. Those omissions make it difficult to assess how results across outcomes would be interpreted or how incomplete follow-up could influence estimates.

Finally, the record distinguishes the study’s safety and tolerability focus from the range of efficacy and pharmacokinetic measures it also lists. That distinction is useful when judging what the design can address, but design descriptions are not results. The case underscores the value of reporting numerical effects and uncertainty alongside endpoint definitions, analysis populations, and analysis methods.

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 central limitation for interpreting the primary endpoint is that numerical results are not reported in the registry record. The endpoint definition, measurement method, timepoints, analysis population, and dispersion measure are identified, but no means, standard deviations, treatment contrasts, confidence intervals, or p-values are available. The observed heart-rate changes and their precision therefore cannot be assessed.

The outcome is measured at Days 20 and 48, and the record says the primary outcome has several categories or timepoints and is not reduced to one comparison. It does not state which contrast should be treated as the principal comparison or how results across the timepoints were intended to be interpreted. The multiplicity plan is not reported. Although 15 outcome measures and 15 analyses are listed, the registry entries do not explain their hierarchy or identify confirmatory analyses.

The primary analysis population includes randomized participants who received at least one dose, analysed according to treatment received, with participants who have data at each timepoint presented. The record does not describe missing-data amounts, reasons, or handling methods. It also does not report an intention-to-treat analysis or a detailed statistical analysis plan. The potential influence of missing measurements and analysis choices cannot therefore be evaluated.

The record does not describe the randomization procedure, allocation concealment, or masking procedures in detail. It identifies a completed study and enrollment of 61, but does not report the original sample-size justification. Safety reporting is limited to group counts and does not provide event-specific terms, severity, timing, or relatedness in the information available for this summary. These limitations constrain interpretation of both efficacy outcomes and safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Tolerability Study of MEDI0382 in Japanese Preobese or Obese Subjects With Type 2 Diabetes — NCT03645421.
• Registry record last updated 2019-12-23; status last verified 2019-12.
• Results first posted 2019-12-23.
• 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

NCT03645421 is a completed Phase IIa, randomized, parallel, double-blind, placebo-controlled study sponsored by AstraZeneca. It enrolled 61 Japanese preobese or obese participants with type 2 diabetes whose glycemic control was inadequate with diet and exercise. The recorded start date is 2018-08-10, and the primary completion date is 2019-01-17.

The study assessed MEDI0382 dose escalation toward 100, 200 or 300 µg/day against placebo over 48 days. The primary endpoint was mean change from baseline in 24-hour heart rate at Days 20 and 48, measured by ambulatory blood pressure monitoring. Secondary outcomes included glycemic measures, time in hyperglycaemia and hypoglycaemia, and MEDI0382 trough concentration.

The registry reports no serious adverse events or deaths in the listed treatment groups, and reports other adverse events in each group. Numerical primary outcome results, missing-data procedures, multiplicity handling, and a detailed statistical analysis plan are not reported in the registry record.