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

1. Trial at a Glance

This page covers the registry results for A Study of Baricitinib and Rifampicin in Healthy Participants (NCT01910311), a non-randomized phase 1 study. The primary outcome is PK: Maximum Concentration (Cmax) of Baricitinib.

2. Clinical Question

3. Trial Design

This is a Phase 1 study of baricitinib and rifampicin in healthy participants. The registry lists 18 enrolled participants, identifies the allocation as non-randomized, states that masking was absent, and classifies the model as single group. The study is marked completed. The registry describes the study as examining the effect of multiple rifampicin doses on a single baricitinib dose, as well as safety and tolerability.

The exposure descriptions distinguish a single oral dose of 10 mg baricitinib on Day 1 from a regimen of oral rifampicin at 600 mg once daily on Days 3 to 11, with a single oral 10 mg baricitinib dose on Day 10. The primary outcome measurement schedule identifies Period 1, Day 1 and Period 2, Day 10, with pharmacokinetic sampling from predose through 48 hours postdose. These period labels and exposure descriptions frame the pharmacokinetic question, but the record does not provide a detailed account of the sequence, allocation process, or visit procedures.

Because the record identifies non-randomized allocation and a single-group model, the exposures should not be read as randomized, like-for-like arms. In particular, the registry does not describe a concurrent control group or a random assignment that would balance other influences between treatment conditions. The arm descriptions and safety entries use separate exposure labels; they should not be interpreted as independent parallel groups without additional design details. The registry record does not report a protocol-level statistical plan, sample-size justification, interim analysis plan, or detailed account of how the study handled departures from the intended dosing schedule.

The registry lists a study duration of approximately 31 days from first dose to the end of study. It records the study start as 2013-08 and primary completion as 2013-10. These administrative details identify the study context; they do not supply missing pharmacokinetic results. Enrollment and completion status likewise do not establish the number of participants with evaluable endpoint data.

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, fixed-sequence, 2-period study conducted in healthy participants to compare the single dose pharmacokinetics (PK) of baricitinib when given alone and when coadministered with rifampicin.

Period 1 (Days 1-2)

Period 2 (Days 3-32)

Analysis population for the primary outcome, as defined in the registry: Participants who received study drug (baricitinib in Period 1 and at least 1 dose of rifampicin and baricitinib in Period 2) 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 enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as PK: Maximum Concentration (Cmax) of Baricitinib, measured over Period 1, Day 1 and Period 2, Day 10: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose.

The primary endpoint is the maximum concentration, or Cmax, of baricitinib, expressed in nanograms per milliliter. Cmax represents the highest measured concentration in the sampling profile after a dose. In pharmacokinetic studies, a peak concentration is used to describe exposure near the top of that profile. It is distinct from measures that describe total exposure over time or the time at which the peak occurs.

The registry specifies the endpoint as a geometric mean and identifies geometric coefficient of variation as its dispersion measure. General statistical explanation: a geometric mean is suited to positive measurements that may vary multiplicatively or have a right-skewed distribution. It is calculated on the logarithmic scale and then expressed back on the original scale. The geometric coefficient of variation describes relative spread around the geometric mean; it is not the same as a confidence interval and does not, by itself, express uncertainty in the estimated mean.

The specified sampling schedule covers predose and postdose measurements at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours in Period 1, Day 1 and Period 2, Day 10. A measured maximum depends on the samples collected and the methods used to derive the pharmacokinetic endpoint. The registry record does not report the Cmax estimates, their dispersion values, or a comparison between exposures. It also does not report a confidence interval or other uncertainty estimate for this endpoint.

The endpoint is relevant to the stated pharmacokinetic question because it describes the concentration peak after baricitinib under the listed exposure conditions. It does not, on its own, describe every aspect of drug exposure, safety, tolerability, or clinical outcome. The endpoint population is restricted to participants with the specified exposures and evaluable pharmacokinetic data, but the number meeting that definition is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint’s statistical description identifies a summary measure and a measure of dispersion, but the registry does not report the calculation details or results. The distinction between those quantities helps clarify what an endpoint result would mean and what cannot be inferred when the values are absent.

What does a geometric mean describe?

General statistical explanation: the arithmetic mean summarizes values by adding them and dividing by their count. The geometric mean instead summarizes multiplicative variation. It is typically calculated by taking logarithms of positive measurements, averaging those transformed values, and converting the result back to the original measurement scale. This can be useful for pharmacokinetic concentrations because concentration data may be right-skewed and variation may be more naturally expressed as proportional rather than additive.

A geometric mean is not a claim that every participant had that concentration, nor does it show the full distribution of observed values. Its interpretation depends on the underlying measurements and the analysis population. Here, the registry identifies the endpoint as a geometric mean of Cmax, but it does not report the estimate, the data distribution, or the number of evaluable participants. The record also does not describe any transformation or model beyond naming the geometric summary.

What is geometric coefficient of variation?

General statistical explanation: a coefficient of variation describes spread relative to a mean, rather than spread in the original units alone. A geometric coefficient of variation is associated with variation on the multiplicative scale. It can help describe how widely positive measurements vary around a geometric mean, but it is not an uncertainty interval for the mean. A dispersion summary and a confidence interval answer different questions: one characterizes variability in measurements, while the other characterizes uncertainty in an estimate under a statistical procedure.

The registry names geometric coefficient of variation as the dispersion measure for Cmax. It does not give its value, a confidence interval, or a detailed formula. It therefore does not allow a reader to assess the observed spread or the precision of the geometric mean. Nor should a dispersion measure be interpreted as a measure of clinical importance.

Why does the sampling schedule matter?

Cmax is derived from concentration measurements over time. The listed schedule includes a predose measurement and samples at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose, for Period 1, Day 1 and Period 2, Day 10. In general, the timing and density of samples shape what can be observed about a concentration-time profile. A measured maximum is tied to available measurements and to any method used to derive the endpoint from them.

The registry gives the planned measurement times but does not describe the assay, the rule for selecting or deriving Cmax, handling of measurements below assay limits, or any procedures for unusual or missing samples. These details are not reported in the registry record. They should not be inferred from the endpoint name or sampling schedule alone.

What does a comparison require?

General statistical explanation: a comparison of two conditions can be expressed in different ways, and the interpretation depends on the design and analysis. An estimate of a difference or ratio is paired with uncertainty information to describe its precision. When measurements are related within participants, an analysis may need to account for that relationship; when groups are independent, a different variance structure may apply. Overlooking dependence can misstate uncertainty. These are general principles, not a claim about the method used in this study.

The registry labels the model as single group and allocation as non-randomized. It describes two exposure conditions and periods, but does not state the statistical model used to compare them or whether participant-level pairing was incorporated. No analysis is listed. Accordingly, the exact comparison method and its assumptions are not reported in the registry record.

General statistical explanation: over-dispersion occurs when observed variability exceeds what a chosen statistical model expects. If a model understates variability, standard errors may be too small and confidence intervals may be too narrow. This is a general concern when selecting a model for variable data; the registry record does not identify an over-dispersion assessment or report a model for this endpoint.

How should planning calculations be read?

General statistical explanation: a sample-size calculation asks what amount of information a future design might need to detect a prespecified effect under stated assumptions. It is sensitive to the assumed effect, variability, allocation, significance level, and statistical model. A calculation based on an observed effect is a planning illustration, not observed power and not a substitute for the trial’s estimated effect or uncertainty. Observed power is especially uninformative when treated as a retrospective summary of a result; the estimate and its confidence interval are more directly useful for understanding precision.

The stated planning assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation. The target effect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning quantities are described as participants per arm; time-to-event calculations instead concern total events. These assumptions concern illustrations and do not establish that the original study used the same design or had a particular power target. The registry does not report the original study’s sample-size justification, and the primary outcome results needed to understand an observed-effect basis are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, but identifies only the Cmax endpoint as primary in the available record. It records 0 analyses. No multiplicity procedure, hierarchy among outcomes, or adjustment for multiple comparisons is reported in the registry record. Without a reported analysis plan and results, it is not possible to determine how outcome multiplicity was handled or whether any inferential claims were adjusted for it.

For the primary pharmacokinetic population, the registry specifies participants who received baricitinib in Period 1 and at least one dose of rifampicin and baricitinib in Period 2, with evaluable pharmacokinetic data. This describes eligibility for that endpoint analysis, but the number of participants meeting the definition is not reported. The enrolled count should not be treated as the analysis denominator because the population definition requires evaluable data and particular exposures.

The record does not report how missing concentration measurements were handled, whether endpoint data were excluded, or how incomplete dosing or protocol deviations affected analysis inclusion. It also does not describe imputation, sensitivity analyses, or a missing-data assumption. These items are not reported in the registry record. Their absence means that readers cannot assess whether missingness may have affected the endpoint summary or comparison.

More generally, analysis-population labels can clarify whether results reflect all enrolled participants, those who received treatment, or a subset with complete and evaluable measurements. The registry’s pharmacokinetic population description is exposure- and evaluability-based, but a formal analysis-population name or a complete accounting of participants by analysis set is not reported. No inferential conclusions about multiplicity or missing-data robustness can be drawn from the registry entry alone.

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 event figures separately for Baricitinib, Rifampicin, and Baricitinib and Rifampicin. Each exposure group lists 18 participants at risk and 0 participants affected by serious adverse events. The figures are group-specific entries; they should not be added to create a total because the record does not establish that the entries represent independent groups of participants.

The record lists 3 participants affected by other adverse events in the Baricitinib group, 3 in the Rifampicin group, and 5 in the Baricitinib and Rifampicin group. These are counts, not descriptions of event type or severity. The registry does not identify the specific non-serious events in the information, so their clinical nature cannot be characterized from these counts.

Death counts are recorded as null rather than as a numerical count. A null entry is not the same as a reported zero; the death information is not reported in the registry record. The list of top serious adverse event terms is empty, so no terms are available to describe.

These safety entries are descriptive registry counts. They do not establish comparative safety because the allocation is non-randomized and the record does not describe a like-for-like randomized comparison. A zero serious adverse event count in the listed group is a report about that group in this record, not proof that an event is impossible or that risks are absent.

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

The study’s stated aim is to examine the effect of multiple rifampicin doses on a single dose of baricitinib and to assess safety and tolerability. Its primary endpoint is baricitinib Cmax, summarized as a geometric mean with geometric coefficient of variation. Those details define the scientific question, but the registry record does not include the primary endpoint values or an analysis comparing the exposure conditions.

As a result, the record cannot show whether Cmax was higher, lower, or similar under the described co-administration condition. It cannot quantify the magnitude of a difference, its uncertainty, or whether an analysis met a statistical threshold. The absence of results should not be interpreted as evidence of no difference. It also should not be treated as evidence of a difference. The endpoint measurements and analysis results are simply not reported in the registry record.

Even with reported pharmacokinetic estimates, a peak concentration would represent one feature of the concentration-time profile. It would not, by itself, summarize all aspects of exposure, safety, tolerability, or clinical outcomes. General statistical explanation: a point estimate communicates magnitude, while a confidence interval communicates precision; neither alone establishes clinical importance. The registry does not report these quantities for the primary endpoint.

The study was conducted in healthy volunteers and is described as Phase 1, single group, non-randomized, and unmasked. That context defines the population and design recorded for this study. It does not establish how findings would apply to other populations or settings. No such extrapolation can be evaluated from the registry results because the primary pharmacokinetic results are absent.

The safety entries report 0 serious adverse events in each listed exposure group, while other adverse event counts are recorded by group. These counts are descriptive and do not supply event details or a randomized comparison. They do not establish that a treatment is safe or unsafe. The record supports a narrow description of the intended exposure conditions, endpoint, and recorded safety counts; it does not support conclusions about the size or clinical meaning of the pharmacokinetic effect.

13. Why This Trial Matters Statistically

This study illustrates a common distinction in clinical research between a clear measurement plan and a reportable result. The registry specifies the pharmacokinetic endpoint, measurement unit, summary type, dispersion measure, and sampling schedule. Those details help define what investigators intended to measure. However, without endpoint estimates and uncertainty measures, readers cannot determine what the study observed or how precisely it estimated the outcome.

It also illustrates why design labels matter when reading comparisons. Non-randomized allocation and a single-group model are not equivalent to a randomized parallel-group design. A contrast between exposure conditions may be scientifically relevant, but its interpretation depends on how the conditions were implemented, how measurements are related, and how the analysis accounted for the design. The registry does not provide enough analysis detail to answer those questions.

The endpoint emphasizes another important statistical distinction: the geometric mean and geometric coefficient of variation describe different features of the data. One summarizes the central tendency on a multiplicative scale; the other describes relative spread. Neither is a confidence interval. A reader needs estimates and uncertainty information to judge both the observed magnitude and the precision of a pharmacokinetic comparison.

Finally, planning calculations and completed-study results serve different purposes. A sample-size illustration under stated assumptions can help frame future design choices, but it cannot recover an unreported outcome or establish observed power. The registry’s limited analysis record makes this distinction especially important. The entry documents a focused pharmacokinetic question and safety counts, while leaving the primary result and its inferential basis unavailable in the registry record.

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 most direct limitation for interpretation is that the primary Cmax results are not reported in the registry record. There are no endpoint estimates, dispersion values, treatment contrasts, confidence intervals, or p values in the recorded information. Therefore, the size, direction, and precision of any pharmacokinetic difference cannot be assessed from this record.

The design is identified as non-randomized, unmasked, and single group. The registry describes baricitinib alone and baricitinib with repeated rifampicin, but it does not provide enough detail to assess sequence effects, potential period effects, or the statistical handling of measurements across periods. It also does not specify whether the analysis treated the conditions as paired observations. These details are not reported in the registry record, so no particular design or analysis method should be assumed.

The primary endpoint population is defined by study-drug exposure and evaluable pharmacokinetic data, but the number meeting that definition is not reported. The record also does not describe missing concentration data, assay procedures, endpoint derivation, protocol deviations, or sensitivity analyses. This leaves uncertainty about the completeness and handling of endpoint measurements.

The safety information is limited to counts by exposure group. Serious adverse events are listed as 0 in each group, but death counts are null and event terms are not available. Other adverse events are counted without descriptions of their nature. The non-randomized design also limits interpretation of these entries as a comparative safety assessment.

The study population is healthy volunteers, and the registry identifies the study as Phase 1. The record does not report results that would allow assessment of how its pharmacokinetic findings relate to other populations. No sample-size justification, formal statistical analysis plan, or multiplicity procedure is reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Baricitinib and Rifampicin in Healthy Participants — NCT01910311.
• 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

The registry record describes a completed Phase 1 study of baricitinib and rifampicin in healthy participants. It lists 18 enrolled participants and identifies the design as non-randomized, unmasked, and single group. The exposure descriptions include a single oral 10 mg baricitinib dose and a co-administration condition with oral rifampicin at 600 mg once daily on Days 3 to 11 and a single 10 mg baricitinib dose on Day 10.

The primary endpoint is maximum baricitinib concentration, summarized as a geometric mean with geometric coefficient of variation. The registry specifies a sampling schedule but does not report endpoint estimates or an analysis. It lists 3 outcome measures and 0 analyses. Serious adverse event counts are 0 in each of the three listed exposure groups; other adverse event counts are 3, 3, and 5, respectively. Death counts are null. The record supports description of the study question and recorded safety counts, but not conclusions about the magnitude or precision of the primary pharmacokinetic result.