A Study of Baricitinib and Ciclosporin in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Baricitinib and Ciclosporin in Healthy Participants (NCT01968057), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib.

2. Clinical Question

The study is intended to examine the effect of ciclosporin on baricitinib pharmacokinetics: the amount absorbed into the bloodstream and the time taken for baricitinib to be removed from the body. The registered primary endpoint is maximum concentration, rather than a direct measure of total drug exposure or removal over time. The study summary also describes evaluating tolerability and safety when baricitinib is given alone and with ciclosporin.

The treatment descriptions place baricitinib alone on Day 1 and baricitinib with ciclosporin on Day 4. The registry identifies the study as non-randomized and single-group, so these treatment conditions should not be read as randomized parallel arms. The posted record does not report a between-condition estimate or its uncertainty. Accordingly, the clinical question is clear, but the magnitude and precision of the reported pharmacokinetic effect cannot be established from the registry record.

3. Trial Design

This completed Phase 1 study enrolled healthy volunteers and was sponsored by Eli Lilly and Company. The registry record lists the start as 2013-10 and primary completion as 2013-12. The study is classified as non-randomized, unmasked, and single-group. These design features are important: the treatment conditions are not independent randomized groups, and the record does not describe a blinded comparison.

The registered treatment descriptions specify a single oral dose of 4 mg baricitinib on Day 1, followed by a single oral dose of 4 mg baricitinib co-administered with a single oral dose of 600 mg ciclosporin on Day 4. This sequence allows pharmacokinetic observations under the two stated conditions, but it does not provide the protections of randomized treatment assignment. The registry record does not report a washout rationale, sequence balancing, or other design details that might clarify possible period or order effects.

Enrollment is reported as 18. That figure does not establish how many participants contributed usable data to the primary endpoint: its population definition requires receipt of study drug in both periods and pharmacokinetic data sufficient to calculate Cmax. The number meeting that definition is not reported in the registry record. The study summary describes a duration of approximately 6 days from first dose to study end, excluding screening and follow-up.

The registry reports three outcome measures and no listed analyses. It does not report a statistical analysis plan, a sample-size justification for the trial, interim analyses, or procedures for handling period effects. Those omissions limit what can be concluded about the intended analysis beyond the endpoint definition and treatment schedule.

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: This was an open-label, 2-period, fixed-sequence study.

Period 1 (Day 1 to Predosing Day 4)

Period 2 (At Dosing Day 4 to Day 7)

Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received study drug (baricitinib in Period 1 and baricitinib + ciclosporin in Period 2) and had PK data to calculate Cmax of baricitinib.

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 enrolled participants

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib, measured over Days 1 and 4: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose.

The primary endpoint is the maximum concentration, or Cmax, of baricitinib in blood, measured in nanograms per milliliter. Cmax is the highest observed concentration in the sampling profile after dosing. It is used in pharmacokinetic studies to describe peak exposure, which can help characterize how a drug behaves in the body under different dosing conditions. It does not by itself describe total exposure over time or the rate at which drug is removed.

The registry specifies pharmacokinetic sampling before dosing and at multiple post-dose times on Days 1 and 4, through 72 hours after dosing. It describes the endpoint using a geometric mean and geometric coefficient of variation. In general, a geometric mean summarizes positive measurements on a multiplicative scale, while a geometric coefficient of variation describes relative variability on that scale. These summaries can be useful when pharmacokinetic measurements are skewed or vary proportionally rather than by a constant absolute amount.

The endpoint population is defined as enrolled participants who received baricitinib in Period 1 and baricitinib with ciclosporin in Period 2, and who had pharmacokinetic data to calculate Cmax. The registry record does not report the resulting geometric means, variability, or a treatment-condition estimate. It therefore does not permit assessment of the observed peak concentration or the precision of any difference between conditions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered endpoint is a pharmacokinetic measure: maximum concentration of baricitinib in blood. The registry identifies the summary as a geometric mean with geometric coefficient of variation. These choices describe how the endpoint was intended to be summarized; they do not provide the observed values. Neither the geometric means nor the coefficient of variation for the treatment conditions is reported in the registry record.

What does Cmax measure?

In general, Cmax is the highest concentration recorded in a series of blood samples after a dose. It is a peak measure, so it answers a different question from a measure that accumulates concentrations across the full sampling period. The registry specifies samples before dose and at post-dose time points on Days 1 and 4, extending to 72 hours after dosing. The scheduled collection times indicate the intended observation profile; they do not reveal the concentrations measured at those times.

Because the endpoint population requires pharmacokinetic data adequate to calculate Cmax, incomplete sampling could affect whether an individual contributes to the endpoint. The record does not report how many participants had usable Cmax data, how missing samples were treated, or whether any imputation or other missing-data method was used. It also does not report the number of participants included in the endpoint calculation.

Why use a geometric summary?

As a general statistical explanation, pharmacokinetic measurements are often positive and can have a right-skewed distribution. A geometric mean summarizes observations after taking logarithms and then returning to the original scale. It expresses a typical value in a multiplicative framework. A geometric coefficient of variation describes the spread relative to the scale of the measurements, rather than expressing spread as an absolute difference from the mean. Neither summary can be reconstructed from the registry record without the underlying results.

A comparison of geometric means is commonly expressed as a ratio, because multiplicative contrasts match the scale of the summary. However, the registry record does not report a ratio, a confidence interval, a p-value, or the method used to compare the two conditions. No such estimate should be inferred from the treatment descriptions or safety counts.

What does uncertainty mean?

In general, a confidence interval is a range of values compatible with the observed data under a specified statistical procedure. A narrower interval indicates greater statistical precision, while a wider interval indicates less precision. The interval does not guarantee that the true effect lies within its endpoints. Since no interval for Cmax is reported in the registry record, the precision of the pharmacokinetic comparison cannot be assessed.

For repeated measurements, general statistical methods may account for relationships among observations from the same participant. That can be important because measurements collected from one person are not necessarily independent. The registry record does not report the model or method used for repeated measurements, nor does it describe any adjustment for period or order. It is therefore not possible to determine how these features were handled in the primary analysis.

What do the planning illustrations represent?

The registry's sample-size assumptions describe a planning illustration computed from an observed effect, not the design basis of this trial. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event illustrations, the stated output is a total number of events; other illustrations are expressed as participants per arm. These assumptions do not establish that the original trial used those design choices, and the illustrations are not observed power.

In general, planning calculations estimate the sample size needed to detect a specified effect under stated assumptions. Their interpretation depends on the assumed effect, variability, allocation, statistical test, and target power. Such calculations cannot replace a reported treatment estimate, and a planning output is not evidence that the study did or did not have adequate power. The registry record does not report a trial-specific sample-size justification or a statistical analysis plan.

What analyses are reported?

The registry lists three outcome measures and no analyses. It does not report the primary endpoint estimates, inferential tests, confidence intervals, multiplicity procedures, or sensitivity analyses. The statistical methods used to generate the posted safety summaries are also not described. These are reporting gaps, not evidence that a particular method was or was not used. The interpretation should therefore remain limited to the endpoint definition, design details, and descriptive event counts available in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures, but it does not report analyses. It does not describe which outcomes were considered primary or secondary beyond the specified primary Cmax endpoint, nor does it report a multiplicity adjustment or a testing hierarchy. When several outcomes or comparisons are examined, general statistical practice may account for the increased chance of false-positive findings. Whether and how that issue was addressed in this study is not reported in the registry record.

The primary endpoint population is defined by treatment receipt in both periods and availability of pharmacokinetic data sufficient to calculate Cmax. The registry does not report the number of participants who met that definition, the amount or pattern of missing pharmacokinetic data, exclusions, or the handling of incomplete profiles. It also does not say whether the analysis followed another defined population. The enrollment figure alone cannot answer these questions.

There is no reported statistical analysis plan, model specification, interim-analysis information, or sensitivity analysis. In particular, the record does not describe handling of period or order effects in the non-randomized, single-group design. These gaps prevent a reader from assessing whether analytical choices were prespecified or how robust any primary estimate would be. Since no primary estimate is posted, there is no reported result for which multiplicity or missing-data adjustments can be evaluated.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events separately for the two treatment conditions. For baricitinib, 0 serious events are listed among 18 participants at risk; for baricitinib plus ciclosporin, 0 are listed among 18 at risk. These figures describe the registry's event counts and denominators. They do not establish that the treatments have identical safety profiles or that serious events could not occur.

Other adverse events are reported for 9 among 18 at risk with baricitinib and 15 among 18 at risk with baricitinib plus ciclosporin. The registry record does not provide event-level details or an inferential comparison for these counts in the registry record described. Because the conditions were not randomized parallel arms and the study was single-group, the counts should be read descriptively rather than as a causal comparison. Death counts are not reported in the registry record.

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

This study addresses a focused pharmacokinetic question: whether co-administration with ciclosporin affects the maximum concentration of baricitinib in healthy participants. It specifies the dose conditions, sampling schedule, endpoint, and endpoint population. The registry record does not report the observed Cmax summaries or a statistical comparison, so it does not establish the direction, magnitude, or precision of the effect.

The study design also limits comparative interpretation. It is identified as non-randomized, unmasked, and single-group, with baricitinib alone described on Day 1 and the combination on Day 4. The registry cautions that these are not like-for-like control arms. Any treatment-condition contrast therefore cannot be treated as if it came from randomized assignment. The record does not explain whether period or order effects were assessed.

The adverse-event summaries show the recorded serious and other event counts for each condition, but these are not a substitute for a comparative analysis. Zero reported serious events in these summaries does not prove absence of risk, and the other-event counts do not by themselves establish that one condition caused more events. The registry does not provide death counts, event-level detail, or inferential estimates in the registry record described.

In general, a result is most informative when an effect estimate is reported alongside a measure of uncertainty and enough analysis detail to assess how it was obtained. Those elements are not reported for the primary endpoint in this record. The record therefore documents the research question and study conduct at a high level, but it does not provide the numerical evidence needed to judge the pharmacokinetic contrast. It also should not be used to infer results for populations beyond the healthy volunteers studied.

13. Why This Trial Matters Statistically

This trial is statistically notable because it asks a pharmacokinetic question using two treatment conditions in a non-randomized, single-group design. The registry describes baricitinib alone on Day 1 and baricitinib with ciclosporin on Day 4. That structure makes the contrast different from a randomized parallel-group comparison and raises the importance of understanding period, order, and within-participant analysis. The registry record does not report how those design features were addressed analytically.

The registered endpoint also illustrates why endpoint definition and result reporting are separate matters. Cmax is a peak concentration measure, with a specified sampling schedule and geometric summary. Those details explain what investigators intended to measure, but they cannot show the observed effect without the actual endpoint values and an estimate of uncertainty. The primary result is not reported in the registry record.

The record further illustrates the distinction between descriptive safety counts and causal comparisons. Event counts are listed for each condition, but the design does not provide randomized treatment allocation, and no inferential safety analysis is reported. These counts can describe what was recorded; they cannot independently establish comparative risk.

Finally, sample-size planning illustrations should not be confused with the design or findings of the trial. The registry identifies them as planning calculations based on an observed effect and specified assumptions, not as the original study's sample-size justification or observed power. Keeping those distinctions clear prevents a planning exercise from being mistaken for evidence about the precision or success of the primary analysis.

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 principal limitation for interpreting the primary question is that the registry record does not report Cmax results, a treatment-condition estimate, or its uncertainty. Although the endpoint, units, summary measure, sampling schedule, and analysis population are described, the number of participants with usable primary endpoint data is not reported. This prevents evaluation of the observed pharmacokinetic effect and its precision.

The treatment conditions were non-randomized and are explicitly not a like-for-like control comparison. Baricitinib alone was described on Day 1, while the combination was described on Day 4. The record does not report whether period or order effects were considered or how within-participant measurements were modeled. Masking was absent, and there is no reported analysis plan with which to assess prespecification.

Safety reporting is also limited. Serious and other adverse-event counts are listed, but the registry record does not provide event-level detail or inferential comparisons in the registry record described. Death counts are not reported. The available counts should not be treated as proof of equivalence or as causal estimates of the effect of ciclosporin.

The registry gives an enrollment figure but does not report endpoint completion, missing-data handling, exclusions, or sensitivity analyses. It lists three outcome measures and no analyses. These omissions restrict assessment of multiplicity and analytical robustness. The findings, to the extent described, concern healthy volunteers; the record does not establish applicability to other populations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Baricitinib and Ciclosporin in Healthy Participants — NCT01968057.
• Registry record last updated 2017-06-06; status last verified 2017-05.
• Results first posted 2017-04-21.
• 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

This completed Phase 1 study enrolled 18 healthy volunteers and examined baricitinib given alone and with ciclosporin. The registered conditions were a single oral dose of 4 mg baricitinib on Day 1 and a single oral dose of 4 mg baricitinib with a single oral dose of 600 mg ciclosporin on Day 4. The study was non-randomized, unmasked, and single-group.

The primary endpoint was baricitinib Cmax, summarized as a geometric mean with geometric coefficient of variation. The registry record does not report the primary endpoint results or a statistical comparison. It lists 0 serious adverse events among 18 at risk in each condition, and other adverse events for 9 among 18 at risk with baricitinib and 15 among 18 at risk with the combination. These are descriptive counts, not randomized comparative estimates.

The record lists three outcome measures and no analyses. Missing-data procedures, multiplicity handling, and details of the statistical analysis are not reported in the registry record.