To Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MEDI6012 in Subjects With Stable Coronary Artery Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MEDI6012 in Subjects With Stable Coronary Artery Disease (NCT02601560), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs).

2. Clinical Question

3. Trial Design

The study was a Phase 2a randomized, double-blind, placebo-controlled trial of MEDI6012 in subjects with stable coronary artery disease. The registry identifies the design as sequential and describes the study as dose escalation. Its stated purpose was to evaluate safety, pharmacokinetics, pharmacodynamics, and immunogenicity after single intravenous and subcutaneous doses. The registry reports enrollment of 48 participants and a completed status.

Participants received one dose on Day 1. The active-treatment groups comprised four intravenous doses—24 mg, 80 mg, 240 mg, and 800 mg—and two subcutaneous doses—80 mg and 600 mg. Separate intravenous and subcutaneous placebo groups were included. The placebo was matched to MEDI6012 by route. The registry does not report the randomization ratio, sequence-generation method, allocation concealment details, or the rules used to move between dose groups.

Double-blinding is qualified in the study summary: subjects and investigators were blinded, while MedImmune was unblinded. Other details about who prepared or administered study drug, and whether outcome assessors were blinded, are not reported in the registry record. The safety endpoint used an as-treated population, defined as all participants who received any amount of study drug. Group-level denominators in the posted safety results range from 4 to 8 participants.

The primary safety observation period extended from baseline (Day 1) up to Day 57. Treatment-emergent events were defined as events occurring after the first dose and up to 57 days after the last dose that were absent before treatment or worsened relative to the pre-treatment state. Since the registry describes single doses on Day 1, the endpoint concerns events during a bounded follow-up period rather than long-term safety. The exact visit schedule and completeness of follow-up are not reported in the registry record.

The registered primary outcome focused on participant counts for TEAEs and TESAEs. Secondary outcomes included baseline-adjusted area under the curve from time 0 to 96 hours for several cholesterol-related measures. Numerical results for those secondary outcomes are not part of the registry entries available for this analysis, so the interpretation stays with the posted safety counts and the registered design.

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: Out of 230 participants, 182 participants were considered screen failures. The remaining 48 participants were randomized to receive the study drug. The 1600 mg dose was omitted based on a greater than expected pharmacodynamics effects at lower doses.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: As-treated Population: All participants who received any amount of study drug were included in this population.

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: As-treated Population: All participants who received any amount of study drug were included in this population.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs), measured over Baseline (Day 1) up to Day 57.

The primary endpoint counts participants with treatment-emergent adverse events and treatment-emergent serious adverse events. An adverse event was defined as any untoward medical occurrence in a participant who received study drug, without requiring a causal relationship to study treatment. A serious adverse event was an event resulting in death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, congenital anomaly, or another outcome considered significant.

“Treatment-emergent” refers to events between the first dose and up to 57 days after the last dose that were absent before treatment or worsened relative to the pre-treatment state. The primary timeframe is baseline (Day 1) up to Day 57. This definition establishes which events are counted; it does not establish that study drug caused an event. The endpoint is therefore a safety description, not a causal attribution by itself.

Counting participants affected is useful for describing how many people experienced events in each treatment group during the observation period. Serious and other adverse events are reported separately, which allows readers to distinguish the serious-event count from the broader count of participants with other events. Such counts do not convey event severity beyond the serious-event classification, the number of recurrent episodes per participant, or the timing and duration of each event. Those details are not reported in the registry record.

For a small, dose-escalation study, participant counts can provide a direct account of observed safety events across dose and route groups. However, they do not by themselves estimate comparative risk precisely, and the endpoint does not determine whether a difference between groups is statistically distinguishable. No inferential comparison for this primary endpoint is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary safety outcome is a count of participants with treatment-emergent adverse events and treatment-emergent serious adverse events. The posted results are presented separately for treatment groups. The registry record does not report a statistical test or effect estimate comparing a MEDI6012 group with placebo for this endpoint. That distinction matters: descriptive counts summarize what was observed, while inferential analyses quantify uncertainty around a comparison under a specified statistical model.

What a participant count captures

A count of affected participants answers how many people in a group experienced at least one event in the category. It is not the same as a count of all event episodes. One participant could experience more than one event, but a participant-based endpoint typically contributes that participant once to the affected-person count for the relevant category. The registry outcome is explicitly described in terms of participants. Event-level frequencies, recurrence, timing, duration, and severity among non-serious events are not reported in the registry record.

The serious-event count uses a defined classification based on outcomes such as hospitalization, a life-threatening experience, or significant disability, as well as other listed criteria. The broader adverse-event definition does not require a suspected causal relationship. Consequently, an event being counted as treatment-emergent does not establish that MEDI6012 caused it. The event must meet the timing and pre-treatment status definition, but causal assessment is a separate question.

How to understand a zero count

When a group has zero observed participants with an event, the direct statement is that none of the participants in that group was recorded with that event category during the defined observation period. It is not evidence that the event is impossible or that its true frequency is zero. General statistical reasoning explains why: the observed sample is only one realization from the population of possible outcomes, and a small group can fail to include an event that occurs infrequently. A confidence interval can communicate uncertainty around an estimated event frequency, but the registry record does not report confidence intervals for these safety counts.

Small denominators also make the results sensitive to individual observations. In a small arm, one additional participant with an event would visibly change the count. Comparing counts across groups without accounting for their denominators would be misleading, because the groups are not all the same size. The posted results identify the number at risk for each group, allowing the counts to be read in their proper group context. No adjusted or unadjusted comparative effect estimate is reported in the registry record.

Why randomization and blinding matter

Randomization is intended, in general, to reduce systematic differences in participant characteristics between assigned treatment groups. Double-blinding can reduce the influence of treatment knowledge on participant reports and clinical assessments. In this study, the registry specifies that subjects and investigators were blinded and MedImmune was unblinded. These design features can support fairer comparisons, but they do not remove the uncertainty caused by small group sizes, missing data, or limitations in outcome measurement. The registry record does not report randomization procedures, concealment details, or the reason for the sponsor’s unblinded role.

The study is described as sequential and dose-escalating. In general, a sequential dose design studies dose groups in an ordered process, but the exact sequence, decision criteria, and any pauses or review procedures are not reported in the registry record. Those details should not be inferred from the listed dose levels alone.

Multiplicity and the other outcomes

The registry lists 24 outcome measures and 6 analyses. The secondary outcomes include baseline-adjusted area under the curve from time 0 to 96 hours for total cholesterol, free cholesterol, cholesteryl ester, high-density lipoprotein cholesteryl ester, non-high-density lipoprotein cholesterol, high-density lipoprotein unesterified cholesterol, non-high-density lipoprotein cholesteryl ester, and non-high-density lipoprotein unesterified cholesterol. When multiple outcomes or analyses are assessed, the chance of at least one apparently unusual result can increase if each is tested separately. General statistical practice may address that concern by prespecifying a primary endpoint, adjusting for multiple tests, or treating secondary analyses as exploratory. The registry record does not report a multiplicity adjustment strategy or a hierarchy of tests.

Planning calculations are not observed power

General sample-size illustrations based on an observed effect are planning exercises, not measures of the probability that the completed trial detected an effect. The stated illustration assumptions 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 illustration is not the trial’s documented design justification. The registry record does not report the original sample-size justification, and the primary safety outcome has several categories or time points rather than one reduced comparison. Any planning figure should therefore be read as a hypothetical design aid, not as an observed result or evidence of adequate power.

For count data, general analysis choices depend on the question, the event frequency, the group sizes, and whether the goal is to estimate absolute event frequencies or compare groups. Methods designed for continuous outcomes would not automatically be appropriate for binary participant-level outcomes. The actual analysis method for the primary safety endpoint is not reported in the registry record. No model, adjustment set, confidence interval method, or test statistic should be attributed to the trial based on the descriptive counts alone.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint contains more than one adverse-event category: treatment-emergent adverse events and treatment-emergent serious adverse events. The registry also lists 24 outcome measures and 6 analyses, with secondary cholesterol outcomes that include multiple lipid-related measurements over a specified area-under-the-curve period. Assessing multiple outcomes can make isolated findings harder to interpret because, in general, repeated statistical testing increases the opportunity for chance findings. The registry record does not report a multiplicity adjustment, a formal testing hierarchy, or which secondary outcomes were considered confirmatory rather than exploratory.

The registry defines the primary safety population as the as-treated population: all participants who received any amount of study drug. That is a clear population definition for the posted safety endpoint. The registry entries do not report an intention-to-treat analysis, a per-protocol analysis, or how participants were handled if assigned treatment but did not receive it. They also do not report the number of participants with incomplete safety follow-up or the amount of missing endpoint data.

Missing-data methods can matter when outcome status is unknown for some participants. In general, excluding participants with missing follow-up can affect an estimate if their event experience differs from that of participants with complete data. Imputation or other approaches require assumptions about why data are missing. The registry record does not report a missing-data strategy, follow-up completeness, or sensitivity analyses. It is therefore not possible to determine from the registry entries whether missing outcomes affected the safety summaries.

The primary outcome’s stated observation period runs from baseline (Day 1) up to Day 57. The registry defines treatment-emergent events relative to treatment initiation and the pre-treatment state, but the detailed event collection schedule and adjudication procedures are not reported in the registry record. Those omissions limit assessment of how consistently events were detected and classified across groups.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures are participant counts by group. No participants were reported with serious adverse events in any group: intravenous placebo (0 of 8), MEDI6012 24 mg IV (0 of 6), MEDI6012 80 mg IV (0 of 6), MEDI6012 240 mg IV (0 of 6), MEDI6012 800 mg IV (0 of 6), subcutaneous placebo (0 of 4), MEDI6012 80 mg SC (0 of 6), and MEDI6012 600 mg SC (0 of 6). The denominator is the number at risk in that group.

These are observations over baseline (Day 1) up to Day 57, not estimates of long-term risk. A zero observed count means no serious adverse event was reported among the participants represented in that group during this period. It does not establish that the true risk is zero, especially with the small group sizes. The registry record does not report confidence intervals or a statistical comparison for serious events.

The separate counts for other adverse events are 3 of 8 for intravenous placebo, 2 of 6 for MEDI6012 24 mg IV, 5 of 6 for MEDI6012 80 mg IV, 2 of 6 for MEDI6012 240 mg IV, 4 of 6 for MEDI6012 800 mg IV, 2 of 4 for subcutaneous placebo, 3 of 6 for MEDI6012 80 mg SC, and 4 of 6 for MEDI6012 600 mg SC. These figures count participants affected rather than total event episodes. The registry does not establish that an event was caused by study drug merely by classifying it as treatment-emergent.

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

The posted results establish what the registry recorded in this completed study: the number of participants with serious and other adverse events in each dose and route group during the defined safety period. No participant in any group was reported with a serious adverse event. The counts of participants with other adverse events varied across the listed groups. These are descriptive findings from a study with small groups, not precise estimates of event rates in a broader population.

The results do not establish that MEDI6012 caused or prevented any particular adverse event. The registry’s adverse-event definition does not require a causal relationship. Nor do the counts establish that one active dose is safer or less safe than another, or that active treatment differs from placebo. Such conclusions would require a clearly specified comparison and an estimate of its uncertainty; those inferential results are not reported in the registry record.

The absence of observed serious events should not be interpreted as proof that serious events cannot occur. A limited number of participants followed over a defined period may not reveal uncommon events or events that arise later. The record also does not report confidence intervals for the event counts, detailed event descriptions, or safety findings beyond the posted categories. These limits make it inappropriate to treat the observed counts as a complete account of all possible safety outcomes.

The study had broader aims involving pharmacokinetics, pharmacodynamics, and immunogenicity, and its secondary outcomes included several cholesterol-related measures. The safety counts alone do not answer those questions. Numerical findings for those measures are not reported in the registry record for this analysis. The results therefore should be understood within the narrow scope of the primary safety endpoint rather than as a complete evaluation of every registered objective.

In general, a trial’s findings are most informative when the population, treatment, comparator, outcome definition, follow-up, and analysis are considered together. Here, the population was adults with stable coronary artery disease; treatment consisted of single IV or SC doses; and the primary endpoint counted affected participants through Day 57. The registry record does not report several details needed for a fuller appraisal, including the sample-size justification, missing-data handling, and formal statistical comparisons. These limits qualify interpretation without changing the basic descriptive meaning of the posted counts.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how safety findings from a dose-escalation study should be read as group-specific counts rather than as definitive comparative estimates. It studied multiple MEDI6012 doses by two routes and included route-matched placebo groups. That structure makes it important to preserve dose and route distinctions when interpreting the results instead of collapsing the groups into a single active-treatment category.

The primary endpoint is based on participants with events, not on event episodes. This distinction matters for safety reporting because a participant can experience multiple events, while a participant count describes whether people were affected. The registry’s separate reporting of serious and other adverse events also makes clear that the categories convey different information. Neither category, by itself, determines causation.

The observed serious-event count was zero in every group, but the small group denominators limit what can be concluded about uncommon outcomes. This illustrates a general statistical point: an event not observed in a small sample is not demonstrated to be absent from the population. Precision and uncertainty matter alongside the raw count. Confidence intervals and comparative estimates would help characterize uncertainty, but they are not reported in the registry record.

The study also illustrates why a design description is not a substitute for a statistical analysis plan. The registry describes randomization, double-blinding, and sequential dose escalation, but the detailed randomization procedures, escalation rules, primary endpoint analysis method, multiplicity strategy, and missing-data approach are not reported. Those details affect how findings should be interpreted and how reproducible the analysis would be.

Finally, the study’s broader pharmacokinetic, pharmacodynamic, and immunogenicity aims sit alongside the safety endpoint. Multiple outcome measures can require careful control of interpretation, particularly when many results are considered. The record’s descriptive safety counts can be understood directly, while broader conclusions require results and analysis details that are not reported in the registry record. The trial therefore offers a useful case for distinguishing observed data from comparative inference and from claims that exceed the endpoint’s scope.

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 safety groups are small: the reported denominators range from 4 to 8 participants. This limits precision and makes the findings less informative about uncommon adverse events. The zero serious-event counts describe only what was observed during the stated period and cannot establish that serious events are absent from the population or would remain unobserved with longer follow-up.

The primary outcome covers baseline (Day 1) up to Day 57, and the study involved single doses on Day 1. The findings do not describe long-term safety. The exact follow-up schedule, completeness of follow-up, and any loss to follow-up are not reported in the registry record. The details of adverse-event collection, coding, review, and adjudication are also not reported.

The trial used multiple active dose groups and two administration routes, alongside separate placebo groups. This creates several possible comparisons, but the registry record does not report a single primary treatment contrast, formal comparative estimates, confidence intervals, or hypothesis tests for the safety endpoint. It also does not report whether any multiplicity adjustment was used. Raw participant counts should therefore not be treated as proof of a dose-related pattern or treatment difference.

Although the primary safety population is defined as participants who received any amount of study drug, the registry does not report an intention-to-treat analysis or provide details on participants who may have been randomized but not treated. The reasons for any differences between planned enrollment and group-level denominators are not reported in the registry record.

The registry identifies the study as sequential and dose-escalating, but the escalation criteria, decision process, and monitoring procedures are not reported. The sample-size justification, missing-data methods, analysis model, and statistical handling of multiple outcomes are also not reported. These omissions limit assessment of design rationale, analysis robustness, and the extent to which the posted safety counts can support comparative conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: To Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MEDI6012 in Subjects With Stable Coronary Artery Disease — NCT02601560.
• Registry record last updated 2018-03-19; status last verified 2018-03.
• Results first posted 2018-03-19.
• 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

NCT02601560 is a completed Phase 2a randomized, double-blind, placebo-controlled study of single ascending doses of MEDI6012 in subjects with stable coronary artery disease. Enrollment was 48. Active doses were 24 mg, 80 mg, 240 mg, and 800 mg by IV administration, and 80 mg and 600 mg by SC administration; separate IV and SC placebo groups were included. Subjects and investigators were blinded, while MedImmune was unblinded.

The primary outcome counted participants with treatment-emergent adverse events and serious adverse events from baseline (Day 1) up to Day 57. The registry reports zero participants with serious adverse events in all groups. Counts of participants with other adverse events ranged from 2 to 5 within the listed groups. The analysis population included all participants who received any amount of study drug.

The registry also lists pharmacokinetic, pharmacodynamic, immunogenicity, and cholesterol-related secondary objectives. Formal comparative safety estimates, confidence intervals, the sample-size justification, multiplicity procedures, and missing-data methods are not reported in the registry record.