Evaluate the Safety and PK of Proellex® in Female Patients With Impaired Hepatic Function and Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluate the Safety and PK of Proellex® in Female Patients With Impaired Hepatic Function and Healthy Adults (NCT00741273), a non-randomized phase 1 study. The primary outcome is Maximum Blood Concentration (Cmax).

2. Clinical Question

The study’s clinical question concerns the safety and pharmacokinetics of orally administered Proellex in female participants with impaired hepatic function and healthy female volunteers with normal hepatic function. Its primary endpoint was maximum blood concentration, or Cmax, assessed over 48 hours after a single dose. The registry also identifies area under the curve from zero to the last time point, AUC0-t, as a secondary outcome.

The question is descriptive rather than a randomized estimate of a treatment effect. Group membership was associated with hepatic-function status, and the listed dose may also differ between groups. Therefore, any group contrast would not isolate the effect of hepatic function from the effect of dose. The registry record does not provide numerical pharmacokinetic results or an adjusted comparison that could resolve this issue.

3. Trial Design

This was a phase 1, open-label, nonrandomized, parallel-group study. The registry lists enrollment of 16 and describes two participant groups: healthy female volunteers and female patients with impaired hepatic function. The study evaluated safety and pharmacokinetics after oral Proellex. Its recorded status is completed.

The registry records the study start as 2008-10 and primary completion as 2009-05. It describes a two-stage, dose-escalation study in the official title, but details of the stages, dose-escalation decisions, or their sequence are not reported in the registry record. The listed masking is none, so the study was open-label.

The allocation was nonrandomized. As a result, the groups were not formed through random assignment, and the record specifically does not support treating them as a like-for-like control comparison. The group descriptions also raise a dose ambiguity: the healthy group is described as receiving 25 mg, while the impaired group’s label says 25 mg and its description says 50 mg. The primary outcome description refers to single doses of 25 mg and 50 mg. The exact mapping of doses to participants is therefore not fully clear from the registry record.

The primary outcome was Cmax in ng/L, summarized as a mean with standard deviation, with a 48-hour timeframe. The registry lists AUC0-t as a secondary outcome and records three outcome measures overall, but does not identify all three in the information available. It records no analyses. A detailed statistical analysis plan, eligibility criteria, stage-specific enrollment, and analysis populations 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

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: ITT and Safety populations were the same

6. Primary Endpoint

The registry lists the primary outcome as Maximum Blood Concentration (Cmax), measured over 48 hours.

Cmax is the maximum concentration of a drug measured in blood after administration. As a pharmacokinetic endpoint, it describes the peak concentration observed during the sampling period. It is distinct from a measure of total exposure: the registry lists AUC0-t, which represents the area under the concentration-time curve through the last measured time point, as a secondary outcome.

The primary outcome was assessed over 48 hours. The registry describes blood samples collected at specified times from 0 through 48 hours after the dose, including early samples and later observations. This repeated sampling is intended to characterize the concentration-time profile and identify its maximum during the observation window. A measured maximum is dependent on the sampling schedule: a peak between scheduled samples may not be captured exactly. This is a general property of sampled concentration-time data, not a finding about this study.

The registry specifies that Cmax is a continuous measure and that the planned summary is a mean with standard deviation. The mean describes the group’s average measured value; the standard deviation describes variability among measurements. These summaries alone do not show the precision of a group comparison, and they do not establish whether observed differences are attributable to hepatic function or dose. Numerical Cmax means and standard deviations are not reported in the registry record. Consequently, the endpoint’s definition and collection window are available, but its observed values cannot be interpreted quantitatively from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary outcome summarized by a mean and standard deviation. It does not report a statistical analysis for that outcome. The following concepts explain how such data are commonly described; they should not be read as methods confirmed to have been used in this study.

What does a mean describe?

For a continuous measure such as Cmax, the mean is the arithmetic average of the observed values in a group. It provides a central summary, but does not show whether observations cluster closely around the average or vary widely. The registry specifies the mean as the outcome parameter, but the numerical group means are not reported in the registry record.

The standard deviation describes the spread of individual measurements around the group mean. A larger standard deviation indicates more variability among observed values in the units of the measurement. It is not the same as the standard error, which describes uncertainty in an estimated mean. The registry identifies standard deviation as the dispersion measure, but numerical standard deviations are not reported. Without the mean, standard deviation, and analysis count for each group, the degree of variability and precision cannot be evaluated.

What does the sampling schedule contribute?

Cmax is defined by the highest measured blood concentration after dosing. The registry describes samples from 0 through 48 hours at listed time points. A denser schedule can describe changes in concentration more closely, but the observed maximum remains the largest value among the scheduled measurements. General explanation: if the actual peak falls between collection times, the measured maximum may differ from the true peak. The registry record does not state how missing or mistimed samples were handled, or whether Cmax was calculated using any additional pharmacokinetic procedures.

AUC0-t is a different pharmacokinetic summary. In general, area under the concentration-time curve reflects exposure over the time interval included in its definition, rather than only the single highest observed concentration. The registry lists AUC0-t as a secondary outcome, but does not provide numerical results or describe the calculation method. Cmax and AUC0-t therefore answer related but distinct questions about concentration data.

What can a group comparison establish?

General explanation: a between-group estimate describes the observed contrast between groups, while a confidence interval can show its statistical precision under an assumed model. A hypothesis test may assess compatibility with a null value, but the test depends on the analysis plan and assumptions. The registry record lists no analyses and reports no comparative estimates, confidence intervals, or p-values. It is therefore not possible to attribute a particular inferential method to this study.

The nonrandomized design matters for interpretation. Randomization, in general, can reduce systematic differences between groups, whereas nonrandom allocation may leave group characteristics imbalanced. Here, the groups represent different hepatic-function categories, and dose wording is inconsistent. This means that a raw contrast, if one were available, would combine features of the groups and cannot automatically be interpreted as an isolated hepatic-function contrast. No adjustment strategy is reported in the registry record.

What do the planning assumptions mean?

The registry’s planning description refers to an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It also describes the effect to detect as a stated fraction of the observed effect. These are planning assumptions, not evidence that a particular analysis was conducted or that the study had a particular probability of detecting an effect. Specific sample-size planning results and the observed effect used for such calculations are not reported in the registry record.

General explanation: a sample-size calculation estimates how many participants would be needed under specified assumptions to target a chosen level of statistical power for a defined effect. Such a calculation depends on the outcome’s variability, the effect size, the significance level, allocation, and the method. It does not show the power actually achieved after a study is completed. The registry’s planning illustration is not a substitute for reported endpoint results, and no observed-power claim can be drawn from it.

Why does variability matter?

General explanation: when measurements are more variable, a group mean is generally estimated less precisely for a fixed amount of data. This is one reason standard deviations and analysis counts are important alongside means. If concentration measurements have a skewed distribution or unusually large values, methods that assume a normal distribution may not describe them well. General explanation: over-dispersion means that variability is greater than a model expects; ignoring it can make uncertainty appear smaller than it is. The registry record does not report whether distributional checks, transformations, or alternative models were considered, so none can be assumed.

In this study, the information needed to judge these features—including numerical endpoint summaries, endpoint-specific counts, and analysis methods—is not reported in the registry record. The design and measurement definitions can be described, but the statistical results cannot be reconstructed from those details alone.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Proellex 25 mg Healthy", "Proellex 25 mg Impaired", "Proellex 50 mg Healthy", "Proellex 50 mg Impaired")
n   <- c(8, 8, 8, 8)
m   <- c(827.5, 587.6, 1589.5, 974)
sp  <- c(312.9, 261.3, 482.3, 400.2)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Proellex 25 mg Healthy  8  827.500  312.900  565.909  1089.091
CARM  Proellex 25 mg Impaired  8  587.600  261.300  369.148  806.052
CARM  Proellex 50 mg Healthy  8  1589.500  482.300  1186.287  1992.713
CARM  Proellex 50 mg Impaired  8  974.000  400.200  639.424  1308.576

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies Cmax as the primary outcome and AUC0-t as a secondary outcome. It records three outcome measures overall, but the remaining outcome measure is not identified in the available record. The number of analyses is recorded as zero. No multiplicity strategy, such as a hierarchy among outcomes or an adjustment to account for multiple statistical tests, is reported in the registry record.

General explanation: when several outcomes or comparisons are tested, the chance of at least one apparently notable result can increase if each test is considered independently. A prespecified analysis strategy can clarify which findings are primary and how multiple tests are handled. This general issue does not establish that multiple inferential tests were performed in this study; the registry lists no analyses.

Missing-data methods are also not reported. The registry does not state how unavailable samples, incomplete concentration profiles, withdrawals, or missing outcome values were handled. It does not report the number of participants contributing data to each pharmacokinetic measure. Enrollment and the safety groups’ at-risk counts do not establish endpoint-specific completeness.

The analysis populations are not reported in the registry record. It is therefore not possible to tell whether pharmacokinetic summaries were intended for all enrolled participants, only participants with evaluable samples, or another defined group. No imputation procedure, exclusion rule, or sensitivity analysis is described. These omissions matter because both the amount and pattern of missing information can affect the interpretation of a mean or group contrast. Without the analysis population and missing-data handling, the numerical estimand intended for the primary endpoint cannot be fully specified.

12. 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 two groups, each with 8 participants at risk for the listed safety outcomes. Serious adverse events affected 0 participants in the healthy group and 0 in the impaired group. The registry also records other adverse events affecting 4 participants in the healthy group and 3 in the impaired group. These are counts, not comparative estimates, and no percentages or statistical tests are reported in the registry record.

The label “other” is distinct from the serious-event count; the record does not list the terms or descriptions for those other events. The serious-event terms list is empty. Death counts are recorded as null, so deaths are not reported in the registry record; null should not be read as a recorded count of zero.

General explanation: an event count describes what was recorded in the observed groups, but does not establish the likelihood of an event in a wider population. In particular, zero recorded serious events in these groups does not establish that serious events cannot occur. The record also does not report event timing, severity details for other events, participant-level exposure duration, or whether events were considered related to Proellex.

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

The registry record documents a completed phase 1 study of Proellex in female patients with impaired hepatic function and healthy female volunteers. It specifies a 48-hour Cmax endpoint, identifies AUC0-t as a secondary outcome, and provides group-level safety counts. Those details establish what the study set out to measure and some of the events recorded.

The record does not report the numerical Cmax or AUC0-t results. It also does not provide confidence intervals, p-values, or a statistical comparison between groups. Accordingly, the degree of pharmacokinetic difference, the uncertainty around any difference, and the precision of the measurements cannot be determined from the registry record. No conclusion about the direction or magnitude of a pharmacokinetic contrast can be drawn from the outcome descriptions alone.

The study is nonrandomized, and the groups are not a like-for-like control comparison. The dose descriptions are inconsistent: the impaired-group arm label says 25 mg, while its description says 50 mg. The healthy group is described as receiving 25 mg, and the primary outcome description mentions 25 mg and 50 mg doses. This wording prevents a fully clear account of the dose mapping. Even a reported group contrast would therefore need careful interpretation, since hepatic-function group and dose may not be separable from the registry entries.

The safety counts are descriptive: zero serious adverse events are recorded in each group, while other adverse events affected 4 participants in the healthy group and 3 in the impaired group. Deaths are not reported. These counts do not establish comparative risk or characterize the unspecified other events.

General explanation: a study can be useful for describing measurements and generating further questions without providing a definitive causal comparison. In this case, the record contains design and safety information but omits the numerical primary outcome and statistical analysis. It therefore does not establish whether Proellex exposure differs by hepatic-function status, nor whether any observed difference would be caused by hepatic function rather than dose or other group characteristics.

14. Why This Trial Matters Statistically

This study raises statistical issues that are especially relevant to small pharmacokinetic studies. Enrollment was 16, and the safety information records 8 participants at risk in each group. With limited group sizes, individual measurements can have a substantial influence on a group mean. General explanation: the mean and standard deviation together help describe both the central value and variation, while an uncertainty interval can help show how precisely a comparison is estimated. The registry does not report the numerical pharmacokinetic summaries or uncertainty intervals needed for that assessment.

The nonrandomized parallel-group design also shapes the question that can be answered. The groups differ in hepatic-function status, and the dose wording is ambiguous. A direct contrast between them would not automatically separate a dose difference from a hepatic-function difference. This is a design and interpretation issue, not merely a matter of selecting a statistical test after data collection.

The primary endpoint and its measurement window are clearly named, and the registry identifies the intended mean and standard-deviation summaries. But without endpoint results, analysis counts, or a stated analysis plan, readers cannot assess precision, missingness, or the suitability of a particular model. The record also identifies multiple outcome measures without describing a multiplicity approach.

These features matter because statistical interpretation depends on more than an endpoint label. The allocation process, dose definition, sample completeness, variability, and analysis method all influence what a comparison means. The record’s planning assumptions describe an illustrative framework, not observed power or evidence of a successful comparison. The study remains informative as a record of a pharmacokinetic and safety investigation, while the absent numerical outcomes and unclear dose wording constrain quantitative interpretation.

15. 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 pharmacokinetic question is that numerical results for the primary Cmax endpoint are not reported in the registry record. The record also does not provide numerical AUC0-t results, confidence intervals, p-values, or comparative estimates. The outcome definitions alone cannot establish the observed concentration levels or the size and precision of a group contrast.

Enrollment was 16, and the safety groups each list 8 participants at risk. Endpoint-specific sample sizes are not reported. The record does not describe whether all enrolled participants completed sampling, whether profiles were evaluable, or how missing samples and incomplete concentration curves were handled.

The nonrandomized design limits causal interpretation. The registry specifically notes that the arms are not a like-for-like control comparison. Moreover, the impaired-group arm label gives 25 mg while its description gives 50 mg; the primary outcome description refers to both doses. This inconsistency makes the group dose assignment unclear. Eligibility details, baseline characteristics, stage-specific procedures, and any adjustment for group differences are not reported in the registry record.

The analysis plan, statistical tests, distributional assumptions, analysis populations, multiplicity handling, and sensitivity analyses are not reported. The registry lists three outcome measures but identifies only the primary Cmax and secondary AUC0-t measures in the available information. It also records no analyses. Finally, the other adverse events are not described by term, and deaths are not reported. Together, these gaps prevent a full assessment of endpoint completeness, inferential precision, event characterization, and the robustness of any comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluate the Safety and PK of Proellex® in Female Patients With Impaired Hepatic Function and Healthy Adults — NCT00741273.
• Registry record last updated 2014-08-28; status last verified 2014-08.
• Results first posted 2014-08-28.
• 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.

19. Record Summary

The registry identifies NCT00741273 as a completed phase 1, open-label, nonrandomized, parallel-group study sponsored by Repros Therapeutics Inc. Enrollment was 16. The recorded start is 2008-10 and primary completion is 2009-05.

The study evaluated Proellex safety and pharmacokinetics in female patients with impaired hepatic function and healthy female volunteers. Cmax, measured over 48 hours and summarized as a mean with standard deviation, was the primary outcome; AUC0-t was listed as secondary. The dose description for the impaired group is inconsistent. Numerical pharmacokinetic results and analyses are not reported in the registry record.

For safety, 0 serious adverse events are recorded in each group, with 8 at risk in each. Other adverse events affected 4 participants in the healthy group and 3 in the impaired group. Deaths are not reported.