Sulforaphane as an Antagonist to Human PXR-mediated Drug-drug Interactions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sulforaphane as an Antagonist to Human PXR-mediated Drug-drug Interactions (NCT00621309), a randomized phase 1 study. The primary outcome is Midazolam Clearance (Pharmacokinetic Measure of Cytochrome P450 3A4 Activity).

2. Clinical Question

3. Trial Design

This is a completed phase I study with randomized allocation, no masking, and a crossover model. Enrollment is listed as 29. The registry record gives a start date of 2008-03 and a primary completion date of 2010-06. It identifies the University of Washington as sponsor and lists adverse drug interactions as the condition.

Three intervention descriptions appear in the record: rifampicin; sulforaphane plus rifampicin; and sulforaphane alone. The rifampicin description states that participants receive 300 mg / 7 days to induce CYP3A4 and have midazolam clearance measured on the 8th day. The sulforaphane descriptions characterize it as a putative inhibitor of ligand activation of PXR. The description of the sulforaphane-alone arm says it is given without the PXR ligand rifampicin.

Although the record identifies a crossover model, it does not report the treatment sequence, period structure, washout procedures, or how the three intervention conditions were assigned within the crossover. The record also does not explain how many participants received each condition or whether all enrolled participants completed the study. The brief summary says the project will recruit 24 volunteers, while the enrollment figure is 29; an explanation for the difference is not reported in the registry record. These details matter for understanding the conduct of a crossover study, but they cannot be reconstructed from the information recorded.

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: 29 participants signed consent form. 23 participants had full measures for data analysis.

Overall Study

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Midazolam Clearance (Pharmacokinetic Measure of Cytochrome P450 3A4 Activity), measured over 7 days.

The primary outcome is midazolam clearance, described as a pharmacokinetic measure of CYP3A4 activity. Clearance characterizes how quickly a substance is removed from the body, and the study uses midazolam clearance as an indicator of CYP3A4 activity. The stated unit is ng*min/ml, the outcome is a mean of a continuous measure, and the timeframe is 7 days.

In the study’s rationale, rifampicin is used to induce CYP3A4 through PXR activation, while sulforaphane is being examined as a possible antagonist of that pathway. Measuring midazolam clearance is therefore intended to provide a pharmacokinetic readout relevant to the proposed interaction. This describes the study’s measurement strategy; it does not establish that a change in clearance occurred or that sulforaphane altered it.

The registry record gives no numerical means, standard deviations, treatment contrasts, confidence intervals, or p-values for this endpoint. It also does not identify a single comparison or result across the recorded time points and categories. Consequently, the endpoint’s definition and rationale are available, but the magnitude and precision of any observed treatment effect are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the design imply?

The record identifies the study as randomized, unmasked, and crossover. Randomization is a method for assigning treatment conditions by chance, which can help limit systematic differences in treatment assignment. The record does not describe the randomization procedure or sequence. Unmasked means the masking field is recorded as none; who knew the assigned condition and whether outcome assessment was masked are not described further.

In general, a crossover design measures participants under more than one treatment condition, allowing comparisons that account for stable differences between participants. This design also makes period and sequence information important. A treatment effect can be difficult to separate from changes over time or effects carried over from an earlier condition if the study’s conduct and analysis do not address them. The registry record does not report the sequence, period structure, washout, or a crossover analysis method. It is therefore not possible to assess those aspects of the design from this entry.

What does the endpoint summary tell us?

The outcome is continuous and summarized as a mean, with standard deviation identified as its dispersion measure. A mean describes the central value of observations, while a standard deviation describes their spread around that mean. These are descriptive statistics. By themselves, they do not provide an estimate of a between-condition effect or its uncertainty. The record names the endpoint and its unit, but it does not contain the numerical means or standard deviations needed to describe the observed outcome.

General statistical explanation: a treatment contrast compares outcome values under conditions of interest. In a crossover study, the contrast may use within-participant information, but the exact method depends on the design and data. A confidence interval conveys uncertainty around an estimate under the model used. Neither a contrast nor a confidence interval is reported for this primary outcome, so the precision of an effect cannot be evaluated.

Can the treatment effect be reconstructed?

No. The registry lists no analysis records, and the primary outcome is not reduced to a single comparison because it has several categories or time points. The record does not give the underlying observations or summary values by condition. A recalculation from posted summary statistics is therefore not available in the information recorded. No direction or magnitude of effect should be inferred from the intervention descriptions alone.

General statistical explanation: an unadjusted recalculation from summary statistics, when possible, is a simple estimate based on those posted summaries and is not a substitute for the sponsor’s analysis. It may not account for design features, covariates, or repeated measures. In this record there are no numerical summaries to recalculate, and there is no sponsor analysis result to compare with a recalculation.

What do the planning assumptions mean?

The registry describes sample-size planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is expressed as a stated fraction of the observed effect. These are planning assumptions, not a statement of the trial’s own design justification. The registry record does not report the trial’s sample-size justification.

The planning values themselves, the observed effect on which they depend, and the specific fractions are not reported in the registry record. The illustrations therefore cannot be interpreted as evidence about the study’s achieved power. More generally, sample-size calculations describe hypothetical design requirements under stated assumptions; they do not measure the probability that a completed study has detected a true effect. Any planning figures should be read as illustrations, not observed power.

Why does uncertainty matter?

General statistical explanation: small or variable datasets can yield imprecise estimates, while larger and less variable datasets can sometimes yield more precise estimates, depending on the design and analysis. A confidence interval is useful because it shows a range of plausible effect values rather than reducing interpretation to a threshold. Without the outcome estimate, variability, and interval, the precision of the trial’s primary result cannot be assessed. Enrollment alone is not enough to determine that precision.

10. Multiplicity, Missing Data and Analysis Populations

The record identifies one primary outcome measure but also indicates that the outcome has several categories or time points and was not reduced to one comparison. The registry record does not describe which time point or contrast was designated as primary for analysis, whether additional comparisons were planned, or how multiplicity was handled. A multiplicity procedure is not reported in the registry record.

General statistical explanation: when multiple outcomes, time points, or comparisons are examined, the chance of finding an apparently notable result can differ from that in a single prespecified test. A statistical plan may define a primary contrast, use an adjustment, or treat additional comparisons as exploratory. These methods cannot be presumed in the absence of documentation, and no adjustment method should be attributed to this study.

Missing-data methods and the amount of missing primary outcome data are not reported in the registry record. The entry does not state whether all enrolled participants contributed outcome measurements under every condition, how incomplete periods were handled, or whether any imputation or sensitivity analysis was used. The analysis population is also not described. Enrollment is listed as 29, but that does not establish the number included in any endpoint analysis.

Because the record lists no analysis records and gives no numerical primary outcome results, the reader cannot assess the consequences of missing observations, the exact comparison set, or the handling of repeated measurements. The absence of these details is a limitation of the registry information; it does not establish that a particular method was or was not used outside the information recorded.

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 registry lists a cross-over trial safety group with 29 participants at risk for serious adverse events and 0 affected. It also lists 29 at risk for other adverse events and 0 affected. No serious adverse event terms are listed. These are the adverse event figures recorded for the trial; they are not primary outcome results and do not provide information about midazolam clearance.

The death count is not reported in the registry record. The entry does not provide event descriptions, observation periods, severity breakdowns beyond the serious and other categories, or treatment-condition-specific safety counts. Because the trial is crossover, the listed group-level figures should not be read as separate counts for each intervention condition. The record does not describe how adverse events were attributed across conditions or periods.

General statistical explanation: an observed count of zero is a description of events recorded in the study population. It does not prove that an event cannot occur or establish the rate that would be expected in a broader population. Safety interpretation depends on the size and characteristics of the population, the duration and completeness of observation, and the way events were collected. Those details are not reported in the registry record. The posted figures should therefore be read narrowly as the counts recorded for the listed group, not as a comprehensive estimate of risk.

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

The registry record establishes that a completed phase I randomized crossover study was conducted, with 29 participants enrolled and midazolam clearance specified as the primary pharmacokinetic measure. It also documents intervention descriptions involving rifampicin, sulforaphane with rifampicin, and sulforaphane alone. Together, these registry entries show the subject of the investigation and the broad design used to examine it.

The record does not report a numerical result for midazolam clearance or an analysis comparing the intervention conditions. It therefore does not establish the size, direction, or precision of any effect. The study description’s proposed mechanism—sulforaphane as a possible antagonist to PXR-mediated induction—should be distinguished from evidence that the mechanism changed in participants. A rationale and a completed trial are not substitutes for reported outcome data.

General interpretation: a result can be considered informative only in relation to its estimate, uncertainty, design, and analysis. Without those outcome details, it is not possible to judge whether the data are compatible with a meaningful increase, decrease, or little difference. The registry entry also does not allow assessment of whether treatment sequence, period effects, or carryover were handled appropriately.

The safety listing records 0 serious adverse events and 0 other adverse events among 29 participants at risk in the cross-over trial group. Those counts describe the registry entry and should not be taken as proof that adverse events are impossible. The death count is not reported in the registry record. Overall, the available information supports a description of the study’s aim and recorded design, but not a conclusion about the primary pharmacokinetic question or a broad claim about safety.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it links a mechanistic hypothesis to a pharmacokinetic measure. The study rationale describes PXR as a regulator involved in CYP3A4 expression and proposes examining sulforaphane in relation to rifampicin-mediated activation. Midazolam clearance is selected as the measure of CYP3A4 activity. This creates a clear conceptual chain from the proposed interaction to a measurable outcome, while leaving the empirical result dependent on the data and analysis.

The crossover design is another important feature. In general, repeated measurements within participants can support comparisons that are less affected by stable differences between people. At the same time, interpretation requires information about sequence, periods, carryover, and the statistical method. Those details are not reported in the registry record, so the potential advantages and risks of the design cannot be evaluated fully from this entry.

The record also illustrates why a study’s question and its reported findings must be kept distinct. The intervention descriptions and endpoint rationale explain what investigators set out to examine. They do not indicate whether the hypothesized effect was observed. Because no numerical primary outcome analysis is recorded, effect magnitude and precision remain unknown from this registry entry.

Finally, the safety counts and enrollment figure have narrow meanings. They describe recorded participants and adverse event counts, but they do not answer the pharmacokinetic question or replace outcome estimates. The central statistical lesson is that a biologically motivated design can identify a relevant comparison, yet interpretation still depends on complete reporting of the comparison, its uncertainty, and the analysis population.

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 main limitation for interpreting this trial from the registry record is the absence of numerical primary outcome results. Although midazolam clearance is named as the primary measure, no condition-specific means, standard deviations, contrasts, confidence intervals, or p-values are reported. The record lists no analysis records and says the outcome has multiple categories or time points rather than one reduced comparison.

Important design details are also absent. The crossover model is identified, but the treatment sequence, period structure, washout, handling of possible carryover, and analysis method are not reported in the registry record. The analysis population, completeness of outcome measurements, missing-data handling, and multiplicity approach are likewise not reported. These omissions prevent evaluation of how the study’s repeated measurements were incorporated into its primary analysis.

The intervention descriptions are incomplete for assessing exposure. The rifampicin description gives a regimen of 300 mg / 7 days and measurement on the 8th day, but sulforaphane doses and schedules are not reported in the registry record. The record does not explain the discrepancy between the brief summary’s stated plan to recruit 24 volunteers and the listed enrollment of 29. It also does not report participant characteristics or eligibility criteria.

The adverse event entry provides group-level counts, but not event observation details or condition-specific counts. The death count is not reported in the registry record. These limits constrain what can be inferred from the safety listing as well as from the primary outcome.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sulforaphane as an Antagonist to Human PXR-mediated Drug-drug Interactions — NCT00621309.
• Registry record last updated 2019-09-06; status last verified 2019-08.
• Results first posted 2019-09-06.
• 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 identifies NCT00621309 as a completed phase I randomized, unmasked crossover trial sponsored by the University of Washington. Enrollment is listed as 29, with a start date of 2008-03 and primary completion date of 2010-06. The study concerns adverse drug interactions and describes conditions involving rifampicin, sulforaphane with rifampicin, and sulforaphane alone.

The primary outcome is mean midazolam clearance, a pharmacokinetic measure of CYP3A4 activity, with a stated timeframe of 7 days. The record does not report numerical outcome results or a primary comparison. It lists 0 serious and 0 other adverse events among 29 participants at risk in the cross-over trial group; the death count is not reported in the registry record. The treatment sequence, analysis population, missing-data approach, and statistical analysis method are not reported.