A Study of Mirikizumab in Participants With Plaque Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Mirikizumab in Participants With Plaque Psoriasis (NCT03718884), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam.

2. Clinical Question

The study asked whether the pharmacokinetics of commonly used drugs and substances changed after participants received multiple doses of mirikizumab. A drug cocktail was given before and after the mirikizumab period, allowing the registry’s planned assessment to focus on concentrations of the cocktail components and their breakdown products in the bloodstream.

3. Trial Design

This phase 1 study is registered as completed and enrolled 29 participants. It began on 2018-10-23, with primary completion on 2019-10-28. The registry describes the design as non-randomized, unmasked and sequential. These features matter for interpretation: the study compares measurements taken at different periods in a planned sequence, rather than comparing independently randomized groups.

In Period 1, participants received a single oral dose of a drug cocktail on Day 1. The listed components were midazolam, warfarin, vitamin K, dextromethorphan, omeprazole and caffeine. In Period 2, participants received mirikizumab 250 mg subcutaneously once every 4 weeks for 16 weeks, from Day 1 to Day 113, and received the second cocktail dose. The registry describes the study as lasting about 23 weeks for each participant, with screening completed within 4 weeks before study start.

Pharmacokinetic sampling for the primary endpoint was scheduled in both periods: before dosing and at specified post-dose times on Day 1, followed by a 24-hour measurement on Day 2 or Day 117. The primary endpoint was maximum observed midazolam concentration. The registry record does not report the numerical results for that endpoint, the number of participants with evaluable data, or reasons for any missing measurements. It also does not report a protocol-level explanation of the sequential design or a sample-size justification.

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.

Period 1 (6 Days)

Period 2 (120 Days)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug cocktail and had evaluable PK data.

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: All participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam, measured over Period 1: Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 2: 24 hours; Period 2: Day 116: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 117: 24 hours; post-dose.

The primary endpoint is the maximum observed concentration, or Cmax, of midazolam in blood plasma, expressed in nanograms per millilitre. It is a pharmacokinetic measure: it describes the highest concentration observed among the scheduled samples after the cocktail dose. The registry specifies that the endpoint is summarized as a geometric mean, with geometric coefficient of variation describing dispersion.

As a general statistical explanation, Cmax is used to characterize the peak concentration reached during the sampling period. Comparing Cmax after the Period 1 cocktail with Cmax after the Period 2 cocktail can describe whether the observed concentration profile differed across the two occasions. The sampling schedule is therefore important: a peak between scheduled collection times could be missed, and the observed maximum is the highest measured value rather than a continuously observed peak.

The registry names this endpoint and its measurement schedule, but numerical Cmax estimates and their uncertainty are not reported in the registry record. Consequently, the direction and size of any difference cannot be described from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is sequential and non-randomized. Participants first received the drug cocktail in Period 1, then received mirikizumab in Period 2 and a second cocktail dose. In a within-participant sequence, measurements from different periods can be compared for the same participant when paired data are available. That approach can reduce the influence of stable differences between participants, but it does not by itself remove effects associated with time, order, changes in health or other period-specific factors. These are general design considerations, not reported findings about this study. The registry record does not describe a statistical model for handling such factors.

What does the primary endpoint measure?

Cmax is the maximum concentration observed among the scheduled pharmacokinetic samples. The endpoint is reported in nanograms per millilitre and is summarized using a geometric mean. As a general explanation, geometric summaries are often used for concentration data when values are positive and vary multiplicatively rather than additively. The geometric coefficient of variation expresses dispersion on a relative scale. The registry does not report the Cmax estimates or the geometric coefficients of variation, so neither the central concentration nor the observed variability can be assessed from the record.

Sampling was scheduled before dosing and at 0.5, 1, 2, 3, 4, 6, 8 and 12 hours on Day 1, with a 24-hour measurement on Day 2 in Period 1 and on Day 117 in Period 2. These are planned collection times. The primary endpoint description does not report actual sampling completeness or the number of evaluable observations at each time. As a general consideration, the timing and completeness of sampling affect how well an observed maximum represents the concentration peak.

How should the sequence be understood?

The same sequence is used for all participants in the registry description; allocation is listed as non-randomized and masking as none. A comparison of Period 1 and Period 2 measurements would therefore be a before-and-after comparison within the study sequence, not a randomized treatment contrast. General statistical interpretation of sequential data requires attention to period and order effects. The registry record does not report whether these were assessed or how they would be accounted for.

The primary endpoint population is defined as participants who received at least one dose of the cocktail and had evaluable pharmacokinetic data. This is a data-based population definition; it does not imply that every enrolled participant contributed to the endpoint. The number meeting this definition and the handling of incomplete or unevaluable pharmacokinetic data are not reported in the registry record.

What do the planning assumptions mean?

The registry describes planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are assumptions for planning illustrations, not evidence that the trial used those assumptions in its own design. They do not establish that the study was randomized or that it had two independently allocated groups. The record does not report a trial-specific sample-size justification.

The illustrations are based on the observed effect, but the numerical primary endpoint effect is not reported in the registry record. The illustrations therefore cannot be independently interpreted from the registered outcome information alone. They are planning calculations, not observed power. The registry also distinguishes time-to-event calculations, which give a total number of events, from other calculations, which give participants per arm.

What inferential details are available?

The registry record does not report the statistical analysis plan, the model used for the primary endpoint, confidence intervals, hypothesis tests, covariate adjustment, interim analyses or a method for addressing multiplicity. No such choices should be inferred from the endpoint summary type or the design labels. As a general explanation, a confidence interval conveys the precision of an estimate by indicating a range of values compatible with the data and the chosen method. Without a reported estimate and interval, neither magnitude nor precision can be described.

The record lists 10 outcome measures and 0 analyses. That distinction does not indicate which outcomes were analyzed or whether any analysis was completed outside the registry entry. For the registered primary outcome, the record identifies what was measured and when, but does not provide the numerical analysis results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, while the analysis count is 0. The record does not identify a multiplicity strategy, such as a hierarchy of outcomes or an adjustment to account for testing multiple outcomes. It also does not report which outcomes were included in a confirmatory analysis. As a general statistical point, examining multiple outcomes can increase the chance of apparently notable findings arising by chance; the importance of that issue depends on the analysis plan and the way results are interpreted. Neither is described in the registry record.

Missing-data methods are not reported in the registry record. The primary endpoint population is limited to participants who received at least one dose of the cocktail and had evaluable pharmacokinetic data, but the record does not state how many participants met that definition, whether any samples were missing, or how incomplete profiles were handled. The enrollment of 29 participants is not itself the endpoint analysis count.

The statistical analysis plan, treatment of outliers, rules for excluding observations, and any imputation method are not reported in the registry record. The same is true of any planned interim analyses. These absences prevent assessment of whether the reported population and methods, if reported elsewhere, followed prespecified rules. They also prevent a detailed evaluation of how missing or unevaluable measurements might affect the primary result.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety entries are organized by study period and exposure. For Period 1: Drug Cocktail, 29 participants were listed at risk and 0 were affected by serious adverse events; 0 were affected by other adverse events, and there were 0 deaths. For Period 2: Mirikizumab, 29 were listed at risk, 0 were affected by serious adverse events, 3 were affected by other adverse events, and there were 0 deaths. For Period 2: Drug Cocktail, 29 were listed at risk, 0 were affected by serious adverse events, 0 were affected by other adverse events, and there were 0 deaths.

These are registry counts for the listed groups and periods. The sequence is non-randomized, and the same participants may appear in more than one period; the counts should not be interpreted as results from independent randomized groups. The record does not provide further details about the three other adverse events, their timing, severity, or relationship to treatment. Zero reported serious events in these entries does not establish that no events occurred outside the reporting scope or that a treatment is safe.

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

The study is designed to examine pharmacokinetics of components of a drug cocktail before and after a period of mirikizumab treatment in participants with plaque psoriasis. The primary outcome is maximum observed midazolam concentration. The registry provides the endpoint definition, schedule and summary measure, but does not report numerical primary outcome results. As a result, it is not possible to describe whether the observed Cmax differed between periods, how large any difference was, or how precise an estimate would be.

The registry’s safety entries report zero serious adverse events in each listed period and three participants with other adverse events in the Period 2 Mirikizumab group. Those figures are descriptive counts in a sequential study. They do not establish a causal safety difference, and the record does not describe the nature of the other events.

The study does not answer whether mirikizumab improves psoriasis: the registered primary question is about pharmacokinetics of midazolam after the cocktail. Nor do the registry entries alone establish whether mirikizumab changes the concentration of every cocktail component, since the primary endpoint named is midazolam Cmax and numerical results for the other measures are not reported in the registry record.

As a general statistical point, a study’s design and endpoint description explain what it set out to measure; conclusions about magnitude and precision require the corresponding estimates and uncertainty measures. Those numerical primary results are not reported in the registry record. The record therefore supports a description of the study question, sequence and reported adverse-event counts, but not a numerical conclusion about the pharmacokinetic effect.

13. Why This Trial Matters Statistically

Drug-interaction studies address whether exposure to other drugs or substances differs when a study treatment is given. This trial’s registered question concerns a cocktail containing midazolam, warfarin, vitamin K, dextromethorphan, omeprazole and caffeine, administered before and after multiple doses of mirikizumab. The primary outcome focuses on midazolam’s maximum observed concentration. Describing this question separately from a treatment-efficacy question helps keep interpretation aligned with what the trial was designed to assess.

Statistically, the sequence is important. Participants received the cocktail in Period 1 and again in Period 2 after mirikizumab dosing; the registry describes no random allocation or masking. A period-to-period comparison is therefore not equivalent to a randomized control comparison. This distinction matters when judging what a difference could mean and which alternative explanations should be considered.

The record also illustrates the difference between defining an outcome and reporting its result. It specifies a pharmacokinetic endpoint, a geometric summary and detailed collection times, but does not report the numerical Cmax results or their precision. Without those estimates, the size and direction of any observed change cannot be evaluated. The posted safety counts can be read descriptively, but they likewise do not create a randomized safety comparison.

The registry record is useful for establishing the study’s stated question, sequence, endpoint and reporting scope. Its statistical value is limited by the absence of numerical primary outcome results and details of the analysis plan. Those limitations should remain visible when interpreting any planning illustrations or descriptive counts.

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.

This is a non-randomized, unmasked, sequential study, not a like-for-like comparison between randomized groups. Because the cocktail was administered in a fixed sequence around the mirikizumab period, period and order effects are general concerns for interpreting a before-and-after contrast. The registry record does not report whether these concerns were addressed analytically.

The primary endpoint’s numerical results are not reported in the registry record. Estimates for the Period 1 and Period 2 Cmax, a between-period contrast, and uncertainty measures are unavailable in the record. Although the primary endpoint population is defined by cocktail exposure and evaluable pharmacokinetic data, the number of participants in that population and the extent of missing measurements are not reported.

The registry identifies 10 outcome measures but does not describe multiplicity handling, the statistical model, missing-data rules, outlier handling or the analysis plan. It also does not report a trial-specific sample-size justification. The planning assumptions described in the registry are illustrations and cannot be treated as a substitute for the trial’s design justification or as observed power.

The safety counts are reported by period, but detail about the three other adverse events in the mirikizumab period is not reported in the registry record. The entries do not provide a randomized comparison, and participants may contribute to more than one period. These design and reporting limits restrict the conclusions that can be drawn from the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Mirikizumab in Participants With Plaque Psoriasis — NCT03718884.
• Registry record last updated 2024-01-29; status last verified 2023-05.
• Results first posted 2024-01-29.
• 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

NCT03718884 is a completed phase 1 study sponsored by Eli Lilly and Company, titled “A Study of Mirikizumab in Participants With Plaque Psoriasis.” The official title describes evaluation of mirikizumab’s effect on the pharmacokinetics of cytochrome P450 substrates in patients with moderate-to-severe plaque psoriasis.

The registry describes a non-randomized, unmasked, sequential design and enrollment of 29 participants. Participants received a drug cocktail in Period 1, followed by mirikizumab 250 mg subcutaneously once every 4 weeks for 16 weeks and a second cocktail dose in Period 2. The primary endpoint was maximum observed midazolam concentration, summarized as a geometric mean with geometric coefficient of variation.

Numerical primary endpoint results and the statistical analysis plan are not reported in the registry record. The safety entries list zero serious adverse events and zero deaths in each period, with three participants affected by other adverse events in the Period 2 Mirikizumab group.