Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction? (NCT01526213), a randomized na study. The primary outcome is Primary Pharmacokinetic Measure: Area Under the Curve (AUC).

2. Clinical Question

The biological rationale in the registry is that grapefruit juice can affect the circulating concentrations of some drugs, while the mechanism for its reported decrease in fexofenadine concentrations is uncertain. The study compares ordinary GFJ with juice described as furanocoumarin-free, alongside water, to investigate that question. This rationale is not itself evidence of what happened in the study.

The design is a randomized, open-label, single-dose, 3-way crossover. In general, a crossover design exposes participants to more than one condition, making it possible to compare conditions within participants. The registry lists six randomized orders for the three conditions, but does not report the results of those comparisons. The posted record therefore establishes the research question and planned measure, not whether the observed data support one explanation over another.

3. Trial Design

The registry identifies this as a randomized, open-label, single-dose, 3-way crossover study in healthy volunteers. Enrollment is recorded as 18, and the study status is completed. The listed sequences assign participants to different orders of water, GFJ, and furanocoumarin-free GFJ. Thus, the study is organized around exposure to all three conditions in varying order, rather than around separate parallel groups receiving only one condition.

In general, crossover studies can compare responses under different conditions within the same participant. This can help account for stable differences between participants, although comparisons may also depend on period effects, carryover, and how the analysis handles the sequence of conditions. The record does not report the washout interval, period-specific procedures, or how sequence and period effects were considered. The sequence descriptions are truncated, so further procedural details are not reported in the registry record.

The study is listed as randomized and unmasked. The record gives no details about the randomization method or allocation concealment. Open-label means masking was not used; the record does not describe any other steps intended to reduce measurement or assessment bias. The sponsor is the University of North Carolina, Chapel Hill. The listed start is 2009-09, and primary completion is 2010-04.

The registry identifies one primary outcome measure and one analysis, but does not give a numerical result, a comparison estimate, or an inferential analysis. The statistical analysis plan, including any model for the crossover structure, is not reported in the registry record. Neither a sample-size justification nor an interim analysis plan is reported. Enrollment and completion status alone cannot establish the precision or reliability of a treatment-condition comparison.

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: No significant events/approaches for overall study following participant enrollment but prior to group assignment. 18 subjects recruited and screened. No exclusions.

Period 1 (5 Days)

Washout 1 (10 Days)

Period 2 (5 Days)

Washout 2 (10 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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Primary Pharmacokinetic Measure: Area Under the Curve (AUC), measured over 0-72 hours.

The primary endpoint is area under the curve (AUC) for fexofenadine over 0-72 hours, measured in micromolar*hr. AUC represents the area under a concentration-time profile and is used in pharmacokinetic research to summarize drug exposure across a specified observation period. AUC is relevant to this question because the study concerns changes in circulating fexofenadine concentrations after exposure to different juice conditions.

The registry specifies a geometric mean as the summary parameter and a full range as the dispersion measure. A geometric mean summarizes positive measurements on a multiplicative scale; a full range describes the span from the lowest to highest reported values. These summaries do not, on their own, show the difference between conditions or how precisely that difference was estimated.

The endpoint's timeframe is 0-72 hours, but the record does not provide the measured AUC values for any condition. It also does not report a treatment contrast, confidence interval, p-value, or the method used to estimate the geometric means. Consequently, the endpoint definition explains what was intended to be measured, but it does not establish the magnitude, direction, or uncertainty of an observed effect. Further endpoint details, including the analysis population and handling of incomplete concentration-time data, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes randomization, no masking, and a 3-way crossover design. Randomization assigns participants to an order of study conditions by chance; in general, this can help prevent systematic selection of an order based on participant characteristics. The listed sequences vary the order of water, GFJ, and furanocoumarin-free GFJ. The randomization procedure itself, including how the sequence assignment was generated or concealed, is not reported in the registry record.

What does crossover mean for the comparison?

In general, a crossover design allows each participant to receive multiple conditions at different times. A comparison can then use within-participant information, rather than relying only on differences between separate groups. That approach may reduce the influence of stable participant characteristics on condition comparisons. It also requires attention to whether outcomes change across periods and whether an earlier condition could affect a later one. The registry does not report the washout interval or how period, sequence, or carryover effects were addressed.

The record calls the study open-label, so masking was not used. In general, lack of masking can affect behavior, measurement, or reporting, depending on the outcome and study procedures. A pharmacokinetic measure is based on measured drug concentrations, but the record does not specify assay procedures, laboratory masking, or other safeguards. The extent to which these issues could affect this endpoint cannot be determined from the posted information.

What does AUC summarize?

In general, AUC summarizes concentration over time across a defined interval. It can therefore represent overall exposure during the specified observation window, rather than concentration at only one time point. Here, the planned interval is 0-72 hours, and the unit is micromolar*hr. The record specifies a geometric mean and full range, but does not report the underlying concentrations, AUC values, or how the endpoint was calculated from measurements.

How should uncertainty be evaluated?

In general, an effect estimate gives the direction and size of a contrast, while a confidence interval communicates its uncertainty. A p-value addresses compatibility with a null hypothesis under stated assumptions, but it does not measure the size or practical importance of an effect. No estimate, confidence interval, or p-value for the primary endpoint is reported in the registry record. The analysis model and its assumptions are also not reported, so the statistical basis for a possible contrast cannot be reviewed.

The planned summary is a geometric mean. In general, geometric summaries are useful for positive measurements that vary on a multiplicative scale. To compare conditions, an analysis might express their relationship on a ratio scale, but the registry record does not report whether such a contrast was used. No ratio or other effect estimate should be inferred from the endpoint summary specification alone.

What can be said about power and sample size?

The record reports enrollment as 18, but a sample-size justification is not reported in the registry record. The available information does not state the anticipated effect, variability, target power, or other assumptions used to plan enrollment. Observed enrollment cannot by itself indicate whether the study was adequately powered for its primary question. No interim analysis plan is reported.

Any planning illustration based on an observed effect would be distinct from the original design justification and would not be observed power. Because the primary effect estimate is not reported in the registry record, there is no reported basis for interpreting such a calculation for this study. The statistical analysis plan, including any transformations, model specification, and treatment of repeated measurements, is not reported.

These general principles describe how the design and endpoint are commonly approached; they do not fill gaps in the record. The posted information identifies the intended measure and broad design, but does not permit reconstruction of the analysis or assessment of its assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome measure and one analysis. It does not report the statistical analysis plan, the number of contrasts tested, or whether any adjustment for multiple comparisons was planned. Since three conditions are listed, more than one pairwise comparison could be relevant to the research question, but the record does not state which comparisons were primary or how any multiplicity was handled. The analysis results are not reported, so the impact of multiplicity on interpretation cannot be assessed.

The analysis population is not reported in the registry record. It is not stated whether all enrolled participants were included in the primary analysis, whether participants had to complete all conditions, or how protocol deviations were handled. Participant flow and the number with usable AUC data are also not reported. Enrollment therefore should not be read as the number contributing to the primary analysis.

Missing-data procedures are not reported. The record does not explain how missing concentration measurements, incomplete observation periods, or incomplete condition sequences were handled, or whether any sensitivity analyses were conducted. In general, missing-data methods matter because conclusions may depend on why measurements are unavailable and on the assumptions used to address them. No such assumptions can be evaluated from the registry record.

The record does not describe adjustments for period, sequence, or other covariates, and does not identify a model for the crossover design. These are analysis details rather than features that can be inferred simply from the study's design label. The record also does not report a prespecified hierarchy of outcomes or a plan for exploratory analyses. These omissions limit assessment of selective analysis and the uncertainty attached to any result.

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.

The adverse-event record lists six randomized sequences. For each sequence, it reports 3 participants at risk for serious adverse events and 0 affected, and 3 at risk for other adverse events and 0 affected. The death entries are null, so deaths are not reported in the registry record. These figures are reported by sequence and should not be interpreted as a complete account of safety across all conditions or periods.

The study is a crossover, but the adverse-event entries are organized by assigned sequence. The record does not explain the event-collection window, whether participants could contribute events during more than one condition, or how events were attributed to a condition. It also does not provide adverse-event terms; the listed serious-event terms are empty. Consequently, the figures do not establish the nature, timing, or condition-specific pattern of events.

In general, absence of reported events in a registry entry does not prove that no events occurred outside the recorded categories or reporting period. Here, the registry lists zero affected for the serious and other event categories in each sequence, but it does not provide additional safety details or a narrative account. Interpretation should remain limited to those entries and their stated sequence-level format.

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

The record establishes that investigators planned a randomized, open-label crossover study of fexofenadine exposure with water, GFJ, and furanocoumarin-free GFJ. The main measure was AUC over 0-72 hours, summarized by a geometric mean. These design details show how the study was intended to address the question of whether furanocoumarins mediate the grapefruit juice interaction with fexofenadine.

The record does not report the AUC values, comparisons, confidence intervals, or p-values. It therefore does not show whether exposure differed among the conditions, how large any difference was, or how precisely a difference was estimated. It also does not support a conclusion about the proposed mechanism. The study's stated rationale is a research question, not a result.

Completion status and enrollment do not substitute for outcome data. They do not indicate how many participants contributed endpoint measurements, whether all conditions were completed, or whether the available data were sufficient to estimate the planned contrasts. Those details are not reported in the registry record.

In general, statistical evidence about a condition difference depends on the estimate, its uncertainty, the analysis assumptions, and the quality and completeness of the data. Those elements are unavailable for the primary endpoint in the posted record. The appropriate interpretation is therefore limited: the registry describes the design and intended pharmacokinetic outcome, while the primary findings are not reported. No claim about a treatment effect or its absence can be made from this information.

13. Why This Trial Matters Statistically

This study poses a mechanistic pharmacokinetic question: whether furanocoumarins explain the change in fexofenadine concentrations associated with grapefruit juice. Its crossover design is relevant because the planned conditions can be compared within participants, in general reducing reliance on comparisons between separate groups. The six listed sequences vary the order in which the conditions are given, making order and period considerations important to the analysis.

The primary endpoint, AUC over 0-72 hours, focuses on drug exposure across a defined observation interval. The record also specifies a geometric mean and full range, which describe the intended summary of the measurements. These choices make clear what kind of outcome the study sought to assess, even though the observed values are not reported.

Statistically, the record illustrates why design information and result information must be distinguished. Randomization, crossover structure, and a defined endpoint describe how a study was organized. They do not reveal the estimated condition differences, their uncertainty, or whether the data support the proposed explanation. The analysis model, missing-data procedures, and multiplicity approach are not reported, further limiting assessment.

The registry record is therefore informative about the question and broad study structure, but not about the answer. That distinction matters when reading completed studies: status and methods cannot replace the estimates and uncertainty needed for statistical interpretation.

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 central limitation for interpretation is that the primary endpoint results are not reported in the registry record. There are no condition-specific AUC values, effect estimates, confidence intervals, or p-values. The direction, magnitude, and precision of any comparison therefore cannot be assessed.

Details needed to evaluate the crossover analysis are also absent. The record does not report washout intervals, period-specific procedures, or how period, sequence, or carryover effects were handled. The analysis model and its assumptions are not reported. Although the randomized sequence structure is described, the randomization method and allocation concealment are not reported.

The record does not provide participant characteristics, condition-specific data counts, participant flow, or the primary analysis population. It does not explain how incomplete concentration-time profiles or other missing data were treated. The sequence descriptions are truncated, and further procedural details are not reported in the registry record.

The registry does not report a sample-size justification, interim analysis plan, multiplicity strategy, or detailed statistical analysis plan. Safety entries are organized by sequence and do not describe event timing or attribution to a condition. These limits mean the record supports a design-level description, but not a comprehensive assessment of the study's results or their robustness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction? — NCT01526213.
• Registry record last updated 2017-05-30; status last verified 2012-12.
• Results first posted 2013-02-04.
• 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

NCT01526213 is a completed randomized, open-label, single-dose, 3-way crossover study in healthy volunteers, with enrollment recorded as 18. It compared fexofenadine exposure with water, GFJ, and furanocoumarin-free GFJ in varying randomized sequences. The stated question was whether furanocoumarins mediate the fexofenadine-grapefruit juice interaction.

The primary pharmacokinetic measure was AUC over 0-72 hours, in micromolar*hr, with a geometric mean and full range specified. The registry record does not report primary outcome values, comparative estimates, uncertainty measures, or detailed analysis methods. The record lists zero serious and zero other adverse events in each sequence; deaths are not reported. The main statistical conclusion is that the design and intended endpoint are documented, but the findings needed to answer the research question are not reported in the registry record.