Study to Evaluate the Effects of MEDI6012 on Apolipoprotein B100 Metabolism: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Effects of MEDI6012 on Apolipoprotein B100 Metabolism (NCT03773172), a randomized phase 2 study. The primary outcome is Fractional Clearance Rate (FCR) of Lipoprotein B (Pools/Day).

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, placebo-controlled crossover study of MEDI6012 in people with stable atherosclerotic cardiovascular disease. The registry lists Columbia University as sponsor and the study as single-center. Its masking designation is quadruple. The record does not specify which roles were masked or how masking was maintained.

The active-treatment description specifies an IV push loading dose of 300 mg MEDI6012 followed by a 150 mg maintenance dose at 48 hours. The placebo arm was intended to mimic active treatment. The primary outcome timeframe was up to 48 hours from the first dose. The registry does not report the timing of all measurements or the details of the placebo schedule.

The crossover model means participants are assigned to treatment conditions in sequence rather than being described only as parallel groups. However, the sequence allocation, period structure, washout interval, and whether any period or carryover effects were assessed are not reported in the registry record. Those details matter because a crossover comparison can depend on within-participant measurements and on the separation between treatment periods.

The recorded enrollment is 7. The posted primary-outcome summaries list n of 5 for MEDI6012 and n of 5 for placebo. The record does not explain how those arm counts relate to enrollment or whether they represent complete crossover pairs. The study is marked terminated; the reason and timing of termination are not reported in the registry record. The listed start date is 2019-01-31, and the primary completion date is 2020-08-31.

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: 7 participants were enrolled; 2 participants withdrew consent prior to randomization and therefore were not included in the Participant Flow.

First Intervention (3 Days)

Washout (6 to 8 Weeks)

Second Intervention (3 Days)

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 were not collected per Arm, thus cannot be presented per Arm.

6. Primary Endpoint

The registry lists the primary outcome as Fractional Clearance Rate (FCR) of Lipoprotein B (Pools/Day), measured over Up to 48 hours from first dose.

The primary endpoint is fractional clearance rate (FCR) of Lipoprotein B, expressed in pools per day. The registry describes FCR as the rate of synthesis and clearance of soluble lipoprotein B in participants per day. The outcome title identifies Lipoprotein B, while the study summary also describes interest in the metabolism of apolipoprotein B100 lipoproteins.

A clearance-rate endpoint is used to characterize the movement of a measured substance through the body over time. In general, a rate-based measure can address aspects of metabolism that a single concentration measurement cannot describe by itself. That is a general interpretation of rate endpoints; the registry does not report the measurement procedure, kinetic model, or assumptions used to estimate FCR in this study.

The stated timeframe is up to 48 hours from the first dose. The posted values are means, with standard deviations, for MEDI6012 and placebo. No confidence limits are posted, and the registry marks values as missing or not estimable for a two-arm comparison of this continuous endpoint. Consequently, the summaries describe the recorded arm-level values but do not provide an inferential estimate of the treatment contrast or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, quadruple-masked crossover design. Randomization is intended, in general, to reduce systematic differences in how participants are assigned to treatment conditions. Masking is intended to limit the influence of treatment knowledge on conduct, assessment, or reporting. The record does not say which people were masked, how the random sequence was generated, or how allocation was concealed, so those procedures cannot be evaluated from the registry entry.

What does crossover mean for the comparison?

In a crossover design, participants receive more than one treatment condition in an assigned sequence. The central comparison can use each participant as their own control, which may reduce the influence of characteristics that remain relatively stable within a person. This is a general feature of crossover analysis, not a description of the analysis actually used in this trial. The registry does not provide the treatment sequences, period-specific outcome values, washout details, or paired treatment differences.

Crossover results can also be affected by changes over time, period effects, or lingering effects from an earlier treatment period. A washout interval and an analysis that accounts for period and sequence can be relevant to interpretation. Whether these issues arose or how they were handled is not reported in the registry record. It is therefore not possible to verify that the posted summaries account for the design's paired structure.

What do the means and standard deviations describe?

The primary outcome is continuous, and the record identifies the reported parameter as a mean with standard deviation as its dispersion measure. A mean gives a summary of the observed values in a group. A standard deviation describes how spread out those values are around the mean. Neither quantity alone describes the uncertainty in a treatment contrast. The posted means are 14.0 for MEDI6012 and 10.0 for placebo; the standard deviations are 6.0 and 5.5, respectively. No arm-level confidence limits are posted.

For a crossover comparison, the variability of within-participant differences is especially relevant. Separate arm means and standard deviations do not reveal how the two measurements are related within participants. Without that relationship, the standard error and confidence interval for a paired contrast cannot be obtained from these summaries alone. The registry explicitly records the two-arm comparison as missing or not estimable and lists no analyses.

Why is no significance test available?

A significance test evaluates how compatible observed data are with a specified null hypothesis under a defined statistical model. The result depends on the estimate, its uncertainty, and the analysis assumptions. No test statistic or p-value is posted for the primary outcome. It would not be sound to infer one from the arm means and standard deviations, especially because the crossover pairing is not represented in the summaries.

More generally, confidence intervals are useful because they communicate both the direction and precision of an estimated contrast. A wide interval may be compatible with a broad range of effects, while a narrower interval conveys greater precision under the model. No confidence interval for the primary treatment contrast is reported, so the range of plausible contrasts cannot be judged.

What can the planning illustration say?

The registry describes planning illustrations as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is specified as a stated fraction of the observed effect. Such quantities are planning illustrations, not observed power and not evidence that the trial had a particular probability of detecting an effect. The record does not report the trial's own sample-size justification. No numerical planning values are included in the registry information used for this interpretation, so no participant requirement can be stated.

In general, observed-effect-based planning can be sensitive to the estimate used as its starting point, especially when the underlying trial is small or the estimate is imprecise. A planning calculation also relies on its stated assumptions and does not replace a prespecified sample-size rationale. Here, the primary comparison is not estimable in the registry record, so a planning illustration based on an observed contrast should be read cautiously and cannot resolve the missing inferential result.

Why does over-dispersion matter?

Over-dispersion is a general concern when outcomes vary more than a statistical model assumes. It can make standard errors too small if the model understates variability, leading to intervals that appear more precise than warranted. The primary endpoint is continuous, and no dispersion model or over-dispersion adjustment is reported. This concept does not establish that over-dispersion occurred in this study; it illustrates why model assumptions and uncertainty estimates matter.

Overall, the registry supports a descriptive reading of the endpoint summaries and a clear statement that the two-arm comparison is unavailable. It does not support a reconstructed inferential result or an assessment of the statistical model used for the crossover data.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("MEDI6012", "Placebo")
n   <- c(5, 5)
m   <- c(14, 10)
sp  <- c(6, 5.5)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  MEDI6012  5  14.000  6.000  6.550  21.450
CARM  Placebo  5  10.000  5.500  3.171  16.829

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome: fractional clearance rate of Lipoprotein B. It also lists one secondary outcome, production rate of apolipoprotein B100, measured in mg/kg/day. The registry record includes 3 outcome measures, but no outcome analysis results are listed. The additional outcome measures and their relationship to the listed primary and secondary outcomes are not specified in the information available for this interpretation.

Multiplicity arises when several outcomes, time points, or comparisons are tested. In general, conducting many tests can increase the chance of at least one apparently notable result unless the analysis plan addresses that issue. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a prespecified approach to multiple outcomes. It is therefore not possible to determine how multiplicity was handled.

The record does not report an analysis population, participant flow, missing-data methods, or reasons for missing outcome values. Although it posts arm counts and means for the primary endpoint, it also marks the two-arm comparison as missing or not estimable. There is no description of whether participants with incomplete measurements were included, how incomplete crossover periods were handled, or whether any imputation was used.

These omissions limit interpretation of the posted summaries. In general, missingness can affect a result when the probability of an unavailable measurement is related to participant characteristics or outcomes. That is a general statistical concern, not evidence that missingness followed a particular pattern in this trial. The registry record does not give enough information to assess that possibility or to identify an intention-to-treat, per-protocol, or other analysis population.

12. 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 posted safety figures list 5 participants at risk in each treatment group. Serious adverse events are recorded for 0 participants in the MEDI6012 group and 0 in the placebo group. Other adverse events are recorded for 1 participant in each group. Deaths are recorded as 0 in both groups. No top serious adverse-event terms are listed.

These figures are counts from the registry entry, not a complete description of the nature, timing, or severity of every event. The record does not list the specific non-serious adverse events, their relationship to treatment, or whether an individual could contribute more than one event. It also does not provide a detailed safety-analysis population or explain how the posted at-risk counts relate to the recorded enrollment.

With the small posted at-risk counts, zero recorded serious events should be read as an observation in this study, not as proof that serious events cannot occur. Likewise, the matching count of other adverse events does not establish that the event types or clinical circumstances were the same in the two groups. These summaries describe what is recorded and do not support broader safety conclusions.

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

The registry record documents a phase 2 randomized crossover study comparing MEDI6012 with placebo for Lipoprotein B fractional clearance rate in people with stable atherosclerotic cardiovascular disease. It posts group means, standard deviations, and arm counts for the primary outcome. The means are 14.0 for MEDI6012 and 10.0 for placebo, with standard deviations of 6.0 and 5.5. The record says that a two-arm comparison of this continuous endpoint is missing or not estimable.

That distinction matters: descriptive summaries report what was observed in the posted groups, while an inferential comparison estimates a treatment contrast and its uncertainty. The latter is unavailable. Without a contrast estimate and an uncertainty measure, readers cannot tell how precise the apparent separation between the means is or how compatible the data are with different possible treatment effects.

The record does not establish why the comparison is unavailable, how the crossover data were analyzed, or whether the posted arm counts represent complete pairs. It also does not report the trial's sample-size justification or an analysis population. The study status is terminated, but the reason for termination is not reported. These gaps prevent a full assessment of the design's execution and of the primary result.

In general, a small study may offer limited precision, but the registry summaries do not support calculating an effect estimate or uncertainty from the posted group-level statistics. Nor do the planning assumptions constitute observed power. The result should not be characterized as evidence for or against a treatment effect on the basis of the means alone.

The record's appropriate contribution is therefore descriptive and methodological: it identifies the intervention, comparator, crossover design, primary endpoint, and posted outcome summaries, while also making clear that the principal comparison is not estimable in the registry. It does not determine a treatment effect, confirm or exclude a clinically meaningful difference, or provide a basis for medical advice.

14. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison cannot be interpreted from group means alone. The primary endpoint is continuous, and the registry posts means and standard deviations for each condition. Yet it also records that the two-arm comparison is missing or not estimable. The missing inferential result is important: readers cannot assess the estimated contrast, its uncertainty, or the analysis supporting it.

The crossover design makes the distinction between group-level summaries and paired information particularly relevant. In general, crossover studies can use within-participant comparisons, but those comparisons depend on the relationship between measurements from the same participant. Separate means and standard deviations do not convey that relationship. The registry does not post paired differences or explain how the crossover structure was handled.

The record also illustrates the need to distinguish enrollment from endpoint counts. Enrollment is recorded as 7, while each treatment-condition summary lists n of 5. The registry does not explain this accounting. Without participant flow and analysis-population details, readers cannot determine how the outcome summaries relate to the enrolled group.

Finally, the study is marked terminated, and the reason is not reported. That status, combined with the unavailable primary comparison, makes transparent reporting of analysis methods and missing data especially valuable. The record gives enough information to identify the study question and descriptive outcome summaries, but not enough to evaluate the primary treatment contrast. This is a useful statistical distinction: a trial may have posted outcome values without providing an interpretable estimate of the effect those values were intended to compare.

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.

Several trial-specific limitations restrict interpretation. The primary two-arm comparison is recorded as missing or not estimable, and no analysis results are listed. There is no treatment-contrast estimate, confidence interval, or p-value for the primary outcome. The means and standard deviations cannot replace those quantities, particularly in a crossover design.

The registry lists enrollment of 7 but posts primary-outcome counts of 5 for each condition. It does not explain the relationship between those figures, the number of complete crossover pairs, or participant flow. The primary-outcome population field is blank. Analysis populations and missing-data procedures are not reported.

Important design details are also absent: the treatment sequence, period structure, washout interval, measurement methods, and handling of period or carryover effects are not reported in the registry record. The masking designation is quadruple, but the masked roles and procedures are not described. The reason the study was terminated is not stated.

The registry lists a secondary production-rate outcome and 3 outcome measures, but outcome-specific analysis results and a multiplicity strategy are not reported. The record also does not provide the trial's sample-size justification. These limitations prevent a complete assessment of the planned analysis, the treatment contrast, and the precision of the result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Effects of MEDI6012 on Apolipoprotein B100 Metabolism — NCT03773172.
• Registry record last updated 2024-11-12; status last verified 2024-10.
• Results first posted 2024-11-12.
• 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

NCT03773172 is a phase 2 randomized, quadruple-masked, placebo-controlled crossover study sponsored by Columbia University. The registry describes a single-center study in people with stable atherosclerotic cardiovascular disease. It is marked terminated. The listed start date is 2019-01-31, and the primary completion date is 2020-08-31.

The active regimen is described as an IV push loading dose of 300 mg MEDI6012 followed by a 150 mg maintenance dose at 48 hours. The primary endpoint is Lipoprotein B fractional clearance rate in pools per day, measured up to 48 hours from the first dose. Posted means are 14.0 for MEDI6012 and 10.0 for placebo, but the two-arm comparison is recorded as missing or not estimable. The registry does not report an inferential result or the reason for termination.