Open-Label, Multiple-Dose, Non-Randomized Study to Assess Drug-Drug Interactions of Proellex® in Female Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label, Multiple-Dose, Non-Randomized Study to Assess Drug-Drug Interactions of Proellex® in Female Subjects (NCT00741468), a na phase 1 study. The primary outcome is Plasma AUC Ratio of Day 1 and Day 8.

2. Clinical Question

The study was designed to assess possible interactions with several cytochrome P450 isoenzymes in healthy female subjects receiving Proellex. For CYP1A2, the listed measure was the plasma paraxanthine/caffeine metabolic ratio. For CYP2D6, it was the dextromethorphan/dextrorphan metabolic ratio. The description does not specify a separate metabolic-ratio definition for the other listed pathways.

This is a pharmacokinetic question, not a clinical-outcome comparison. The endpoint concerns exposure measures over the study period. The registry record does not report numerical results that would establish the size, direction, or precision of any day 8 to day 1 change. It also does not report a direct comparison with an untreated group.

3. Trial Design

This was an open-label, multiple-dose, non-randomized phase 1 study, recorded as a single-group design. The registry lists enrollment of 18 and a completed status. The listed study start is 2008-07, and primary completion is recorded as 2008-09. The brief summary describes a total study duration of 6-8 weeks.

All subjects were assigned to the same study group in the registry description. The listed regimen was Proellex 50 mg once daily alongside probes for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The registry record does not describe a randomized allocation or a like-for-like control arm. Its allocation field is recorded as not applicable, consistent with the single-group design.

The primary endpoint compares day 8 AUC with day 1 AUC. In the context of this study, these are repeated measurements over time within the study rather than outcomes from separate randomized groups. Blood samples were collected before and after dosing, and urine samples were collected after dosing, according to the brief summary. The outcome timeframe is listed as 8 days.

Open-label means the study was not masked. The registry record does not report procedures to conceal treatment or reduce awareness of the study regimen. Because there is no randomized control group, changes between the two measurement days cannot be interpreted as a randomized treatment contrast. The record does not give further details about the sequence or timing of each probe dose, the probe doses themselves, or the full visit schedule.

The registry classifies the study as completed, but completion status does not supply an estimate of the primary endpoint. Although the record lists one outcome measure, it lists no analyses. The planned statistical methods, including any sample-size justification or prespecified analysis plan, are not reported in the registry record.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: One subject had concentrations of Proellex (CDB-4124 and CDB-4453) that were below the lower level of quantitation at all time points tested and was excluded from the pharmacokinetic analyses.

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 subjects enrolled

6. Primary Endpoint

The registry lists the primary outcome as Plasma AUC Ratio of Day 1 and Day 8, measured over 8 days.

The primary endpoint is titled Plasma AUC Ratio of Day 1 and Day 8. Its unit is the ratio of geometric means for day 8 to day 1, and the listed dispersion measure is a 90% confidence interval. The registry describes the comparison as an assessment of possible inhibition during administration of Proellex 50 mg once daily.

AUC summarizes drug concentration over time. In general, comparing AUC measurements can describe whether systemic exposure differs between measurement periods. A ratio expresses the day 8 geometric mean relative to the day 1 geometric mean; the ratio is not a direct clinical outcome. The registry record does not provide the actual ratio or its confidence interval, so the direction and magnitude of the observed comparison cannot be described.

The pathway-specific measures include the plasma paraxanthine/caffeine metabolic ratio for CYP1A2 and the dextromethorphan/dextrorphan metabolic ratio for CYP2D6. These ratios are used as probe-based indicators of activity in the respective pathways. The description also lists CYP2C9, CYP2C19, and CYP3A4 probes, but does not give additional ratio definitions in the endpoint description.

In general, a confidence interval communicates uncertainty around an estimate. Its width helps indicate how precisely the data estimate the underlying ratio, under the analysis assumptions. A 90% confidence interval does not itself state whether an interaction was clinically important. Here, neither the endpoint estimates nor their intervals are reported in the registry record, so the posted information does not show their precision or whether they support a particular interpretation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a ratio of geometric means for day 8 to day 1, accompanied by a 90% confidence interval. It does not report the analysis method used to obtain those estimates, the model specification, or numerical results. The explanations below describe the statistical ideas involved in interpreting this type of endpoint in general, rather than asserting which procedures were applied in this study.

What does an AUC ratio represent?

AUC is an exposure summary based on concentration measurements over time. For this study, the listed comparison is between measurements on day 8 and day 1. A ratio of geometric means expresses one period relative to the other. In general, ratios are useful when the scientific question concerns proportional change, rather than a difference in the original measurement units.

Geometric means are based on a multiplicative scale. In general statistical practice, analyses of positive, right-skewed pharmacokinetic measures may use a logarithmic scale and then transform estimates back to the ratio scale. The registry record does not report whether that method, or another method, was used. It also does not specify whether estimates were adjusted for covariates or how repeated measurements were handled.

How should the confidence interval be read?

A confidence interval describes uncertainty in an estimated quantity under the assumptions of the analysis. In general, an interval that spans a broad range indicates less precision than a narrower interval. Its interpretation depends on the data, analysis procedure, and confidence level. The registry lists a 90% confidence interval for the endpoint, but does not provide the interval limits. Its precision therefore cannot be assessed from the posted record.

A confidence interval is not a guarantee that the true value lies within a particular calculated interval, and it does not by itself decide whether a difference matters clinically. Interpretation also depends on the endpoint scale, scientific context, and any prespecified criteria. No such criteria are reported in the registry record. Without the estimate and interval, neither statistical uncertainty nor the relation to any decision threshold can be evaluated.

What do metabolic ratios contribute?

The endpoint description identifies paraxanthine/caffeine as the CYP1A2 metabolic ratio and dextromethorphan/dextrorphan as the CYP2D6 metabolic ratio. In general, probe substrates and their metabolites can be used to characterize enzyme-pathway activity. The record also names probes for CYP2C9, CYP2C19, and CYP3A4, but it does not provide corresponding outcome definitions beyond the AUC-ratio description. The record does not give probe doses or detailed sampling schedules.

These probe-based measures are pharmacokinetic indicators, not direct measures of clinical benefit or harm. An estimate would need to be interpreted with its uncertainty and the pathway-specific measurement definition. No pathway-specific numerical estimates are reported in the registry record.

Why does over-dispersion matter in general?

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If it is ignored, standard errors and confidence intervals can be too optimistic, and tests can be miscalibrated. Whether over-dispersion is relevant depends on the outcome and model. The registry does not report a model or a dispersion assessment, so it is not possible to say whether this issue arose in this study.

What can the planning illustrations show?

Planning illustrations are not observed power and do not add findings to a trial record. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Those assumptions describe an illustration, not this study's single-group, within-study comparison. The registry record does not report the trial's own sample-size justification. The illustrations should not be read as a retrospective measure of whether the study had adequate power.

Most importantly, statistical methods cannot recover an unreported primary estimate. The registry lists no analyses, so there is no basis to evaluate model fit, test results, interval coverage, or the robustness of the primary analysis. These details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The endpoint description spans several cytochrome P450 pathways: CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. It specifically identifies metabolic ratios for CYP1A2 and CYP2D6, and the outcome is described in terms of day 8 and day 1 AUC. Considering several pathways can create a multiplicity question: in general, making several statistical comparisons can increase the chance of finding an apparently notable result by chance if each is interpreted separately.

The registry record lists one outcome measure and no analyses. It does not report how results across the pathways were organized, whether one was considered primary among the pathway-specific assessments, or whether any multiplicity adjustment was planned or used. No adjustment method or hierarchy of tests is reported in the registry record. With no numerical results, the impact of multiplicity on interpretation cannot be assessed.

For missing data, the record states that one subject had concentrations of Proellex components CDB-4124 and CDB-4453 below the lower level of quantitation at all tested time points and was excluded from pharmacokinetic analyses. It does not explain how below-quantitation observations were handled, whether any other measurements were missing, or whether exclusions differed by pathway. It also does not report a sensitivity analysis.

The enrollment figure is 18, but the registry does not give pathway-specific analysis counts or a complete analysis-population definition. The planned analysis population, handling of protocol deviations, and any imputation methods are not reported in the registry record. The single documented exclusion should therefore be described as reported, without assuming that it was the only source of missingness or that all outcomes used the same participants.

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 lists 18 subjects at risk for serious adverse events and 0 subjects affected. It also lists 18 subjects at risk for other adverse events and 13 subjects affected. These are counts of subjects, not counts of all individual event episodes. The registry record does not provide the terms for the other adverse events in this summary.

No serious adverse event terms are listed. The deaths field is not reported in the registry record. A zero count for serious adverse events in this group describes the posted observation; it does not establish that serious events are impossible or that the study can rule out uncommon events.

The adverse-event counts do not establish causality. The registry record does not report whether events were considered related to Proellex, a probe drug, or another cause, nor does it give severity or timing details. The open-label, single-group design also does not provide a randomized safety comparison. These counts should be read as a descriptive summary of reported events, separate from the pharmacokinetic endpoint.

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

This trial asks a focused pharmacokinetic question: how day 8 exposure measures compared with day 1 measures during administration of Proellex and cytochrome P450 probes in healthy female subjects. Its endpoint description specifies a ratio of geometric means and a 90% confidence interval. These design details make clear what the study intended to assess.

What the posted record does not show is the result of that comparison. There are no reported ratios, confidence intervals, or analyses. Consequently, this record cannot establish the direction, magnitude, or precision of the measured differences for the listed pathways. It cannot show from the posted analysis whether a particular pathway was inhibited, or how large any change was.

The study is not a randomized comparison of Proellex with a control treatment. Day 1 and day 8 are measurement periods within a single-group study. General statistical interpretation of a within-study comparison must account for the design and cannot be restated as a randomized between-group treatment effect.

The study also does not answer questions about clinical outcomes. A pharmacokinetic endpoint based on AUC and metabolic ratios is not itself evidence of clinical benefit or harm. The registry record does not report a clinical efficacy endpoint or connect any pharmacokinetic measure to a clinical decision threshold.

The safety summary is likewise descriptive. It records no subjects affected by serious adverse events and other adverse events affecting 13 subjects, but event attribution and detailed terms are not reported. These counts should not be used to make a causal or comparative claim.

Thus, the record is informative about the study's population, regimen, design, endpoint, and reported event counts. It is not sufficient to draw a quantitative conclusion about drug-drug interactions. Missing result estimates should be understood as missing information in the registry record, not as evidence of no effect or evidence of an effect.

13. Why This Trial Matters Statistically

This study is statistically interesting because it illustrates a common early-phase approach: using pharmacokinetic measurements and probe drugs to examine several enzyme pathways over time. The design compares day 8 with day 1 in the same single-group study. That structure differs from a randomized comparison between separate groups and calls for careful description of exactly what the ratio represents.

The endpoint combines multiple ideas that readers need to keep distinct. AUC summarizes exposure; a geometric-mean ratio describes a relative comparison; and a confidence interval conveys uncertainty. These components are useful only when the estimate and its interval are available. In this record, the endpoint is defined but its numerical findings are not reported, which makes the distinction between a planned measure and a posted result especially important.

The study also includes probes for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Assessing several pathways raises general questions about how multiple comparisons are interpreted, whether a primary analysis was selected, and how uncertainty is handled across results. The registry record does not describe those analysis choices. Readers should not infer a multiplicity strategy from the list of probes alone.

Finally, the record documents an exclusion from pharmacokinetic analyses because concentrations were below the lower level of quantitation at all tested time points for one subject. This is relevant because analysis populations and handling of measurements can affect interpretation. The record does not give the analysis counts or further missing-data details. The case therefore shows why design and endpoint descriptions matter, while also showing the limits of interpretation when methods and estimates are not posted.

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 the primary endpoint is that numerical results are not reported in the registry record. There is no day 8 to day 1 ratio, 90% confidence interval, or analysis output. Although one outcome measure is listed, the registry lists no analyses. This prevents assessment of the observed direction, magnitude, and precision.

The design was open-label, non-randomized, and single-group. There is no randomized control group described, so the study does not provide a randomized between-group estimate. The comparison is across measurement days during the study. Details that would clarify the timing and conduct of the regimen, including probe doses, are not reported in the registry record.

The enrolled population was healthy female subjects, and the record lists enrollment of 18. The findings, if reported, would need to be interpreted in the context of that study population and the phase 1 design. One subject was excluded from pharmacokinetic analyses because Proellex component concentrations were below the lower level of quantitation at all tested time points. The record does not give pathway-specific analysis counts or explain whether other measurements were missing.

The registry does not report the analysis model, prespecified criteria for interpretation, sample-size justification, multiplicity approach, or sensitivity analyses. It also does not report the detailed results for each probe pathway. These omissions restrict evaluation of how the planned endpoint was analyzed and how reliable or generalizable any estimate might be. The posted safety summary gives counts, but not detailed event terms or attribution for the other adverse events.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open-Label, Multiple-Dose, Non-Randomized Study to Assess Drug-Drug Interactions of Proellex® in Female Subjects — NCT00741468.
• Registry record last updated 2014-08-22; status last verified 2014-08.
• Results first posted 2014-08-22.
• 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 examined possible drug-drug interactions of Proellex in healthy female subjects. It was open-label, non-randomized, and single-group, with 18 participants enrolled. The listed regimen was Proellex 50 mg once daily with probes for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.

The primary outcome compared day 8 with day 1 AUC using a ratio of geometric means and a 90% confidence interval. The endpoint description identifies metabolic ratios for CYP1A2 and CYP2D6. Numerical endpoint estimates and analyses are not reported in the registry record. One subject was excluded from pharmacokinetic analyses because Proellex component concentrations were below the lower level of quantitation at all tested time points.

The safety summary lists 0 of 18 subjects affected by serious adverse events and 13 of 18 affected by other adverse events. Deaths are not reported in the registry record. The posted information describes the design and planned assessment, but does not support a quantitative conclusion about the pharmacokinetic comparison.