Determination of the Lowest, Safe and Effective Dose of Proellex: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Determination of the Lowest, Safe and Effective Dose of Proellex (NCT01187043), a randomized phase 1, phase 2 study. The primary outcome is Induction Amenorrhea.

2. Clinical Question

The central statistical question is about the pattern of observed participant counts across the dose groups, not about a formally estimated dose-response relationship. The registry lists five doses, but it does not post an inferential analysis, confidence intervals, or a reported comparison test for the primary outcome. The posted numbers therefore describe participants meeting the outcome definition in each listed group; they do not by themselves establish whether differences between doses are more than could be explained by sampling variation.

The record describes a placebo run-in, but it does not provide primary outcome counts for a separate placebo group. It also identifies ARM 1 as a dose group rather than a placebo group. Consequently, the posted primary outcome counts allow a descriptive reading of the dose arms, but not a direct numerical comparison with placebo from the results listed in the registry record.

3. Trial Design

The registry describes a randomized, single-blind Phase I/II study, with a crossover model and an enrollment of 52. The study title refers to a single-blind, placebo run-in, Phase I/II study comparing five oral doses of Proellex. The recorded intervention is Proellex, and the five arm descriptions identify doses of 1 mg, 3 mg, 6 mg, 9 mg, and 12 mg.

There is a difference in how the registry characterizes the design across its fields. The model is listed as crossover, while the primary outcome description says the five doses will be compared in an escalating-dose, to independent groups, against a run-in placebo treatment period. Those descriptions do not provide enough information to reconstruct the sequence of treatment periods, the allocation schedule, or how any within-participant comparisons were handled. Those details are not reported in the registry record.

The study started in 2010-08, reached primary completion in 2012-03, and is listed as completed. These dates describe the study record; they do not provide details about recruitment pace, follow-up beyond the stated primary endpoint timeframe, or timing of analyses. Those details are not reported in the registry record.

The listed enrollment is a study-level figure and should not be assumed to equal the analyzed population for every outcome. The primary endpoint population is described as per protocol, conditioned on trough levels during the dosing period. The arm-level counts posted for that outcome are therefore best read in the context of that defined population rather than as a complete accounting of everyone enrolled. The number randomized, the number completing each treatment period, and the handling of participants outside the per-protocol definition are not reported in the registry record.

Single blinding is recorded, but the registry does not identify which people were masked or describe how masking was maintained. The randomization method, allocation concealment, washout or carryover procedures, and details of the placebo run-in are not reported in the registry record. Without those particulars, the design labels provide useful orientation but do not allow a full assessment of how treatment assignment and period effects were managed.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol: subjects who exhibited trough levels of proellex on at least 7 of the 10 weekly visits during the dosing 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.

Population: ITT

6. Primary Endpoint

The registry lists the primary outcome as Induction Amenorrhea, measured over 10 weeks.

The primary endpoint is titled Induction Amenorrhea and is expressed as a number of participants. The description defines it through suppression of ovulation and/or menses, assessed with ovulation timing kits and a daily diary for bleeding. Its stated timeframe is 10 weeks. The endpoint population is per protocol: subjects who exhibited trough levels of Proellex on at least 7 of the 10 weekly visits during dosing.

This type of endpoint is intended to capture whether the treatment period was associated with the prespecified menstrual and ovulatory outcome, rather than to quantify the duration or degree of menstrual suppression. The registry’s use of ovulation timing kits and a daily bleeding diary indicates the stated sources for determining the outcome, but it does not describe operational rules for resolving conflicting diary and kit results. Such rules are not reported in the registry record.

Because the posted measure is a participant count, the results indicate how many people in each arm were recorded as meeting the endpoint definition. They do not communicate the timing of onset, persistence across the full period, or separate counts for ovulation suppression and menstrual suppression. Those details are not reported in the registry record.

The outcome’s per-protocol definition is important for interpretation: the counts relate to participants meeting a trough-level condition, not necessarily every participant enrolled or randomized. The registry does not report a corresponding intention-to-treat result or explain how participants without the required trough measurements were treated in the endpoint analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry posts a binary primary endpoint as participant counts. A binary endpoint records whether each participant met a stated condition or did not meet it. Here, the condition is induction of amenorrhea, with the outcome described through suppression of ovulation and/or menses. The results list the number meeting the condition and the outcome denominator in each arm. This format is direct and easy to read, but it does not by itself describe uncertainty around the counts or quantify a between-arm effect.

What do the counts tell us?

Each arm’s result is a descriptive summary of the participants represented in that arm’s endpoint analysis. It answers how many met the endpoint definition, not why they did so or what would have happened to those same participants under a different dose. A causal treatment comparison depends on the design and analysis as well as the observed counts. Although randomization is listed, the method of allocation and the statistical approach used for this outcome are not reported in the registry record.

For a binary outcome, analysts commonly compare groups using an absolute difference in event proportions, a relative measure, or a regression model. These methods answer different questions and can produce different numerical summaries. No such comparison estimate is posted for this endpoint. The available count data should not be converted into a new effect measure when the registry does not report one. There are also no confidence intervals or p-values posted for this primary outcome.

Why does the analysis population matter?

The endpoint is defined for a per-protocol population that required trough levels of Proellex on at least 7 of the 10 weekly visits during dosing. A per-protocol analysis focuses on participants who met specified study conditions. As a general statistical consideration, restricting an analysis this way can make the analyzed group differ from the randomized group, particularly if eligibility for the analysis is related to adherence, exposure, health, or outcome. The registry does not report how many participants met or failed this condition, why any participant did not meet it, or whether a separate analysis of all randomized participants was performed.

The posted group counts include an outcome denominator for each dose arm, but the record does not explain how missing diaries, missing ovulation-kit readings, or incomplete trough measurements were handled. Missing-data handling is not reported in the registry record. As a general matter, excluding participants with incomplete outcome information, treating missing observations as failures, or using an imputation method can lead to different results; the chosen approach should be documented to assess its influence.

How should uncertainty be understood?

A confidence interval is a range of values constructed by a statistical method to express uncertainty around an estimate. In general, an interval that is wider indicates less precision, while a narrower interval indicates greater precision under the assumptions of that method. The registry does not post confidence intervals for the primary endpoint, so the precision of any difference between dose groups is not quantified in the record. Raw counts alone are not a substitute for an interval or a formal comparison.

A p-value, in general, measures how incompatible observed data are with a specified statistical null model, subject to the assumptions of the test. It does not measure the probability that a treatment works, and it is not an estimate of effect size. No primary endpoint p-value or test result is posted. The choice of test, whether it accounted for the recorded crossover model, and the significance threshold used for trial analyses are not reported in the registry record.

What design details affect the analysis?

The record lists randomization and a crossover model, but the primary endpoint description refers to escalating doses in independent groups and a placebo run-in. General crossover analyses often need to account for the fact that the same participant may contribute observations under more than one condition, as well as possible period or carryover effects. Independent-group analyses instead compare outcomes from different participants assigned to different groups. Because the registry’s descriptions point to different analytical structures and do not explain the treatment sequence, no particular method should be presumed. The analysis of repeated observations, if any, is not reported in the registry record.

Blinding can reduce some forms of bias, but the label single blind does not identify who was masked or how masking was maintained. General methods considerations include whether participants, investigators, or outcome assessors knew treatment assignment, and whether outcome measurement could be influenced by that knowledge. Those operational details are not reported in the registry record. The use of daily diaries and ovulation timing kits is described, but the record does not report validation procedures, adjudication rules, or methods for handling disagreement between measures.

What can be inferred from the posted analysis record?

The registry lists one outcome measure and no posted analyses. That means the record offers the arm-level outcome counts but no inferential analysis to evaluate contrasts or uncertainty. A lack of posted analysis is not evidence that no analysis was conducted; the analysis results and statistical methods are not reported in the registry record. The record also does not report a statistical analysis plan, model specification, covariate adjustments, handling of multiple dose comparisons, or any interim analysis procedures.

General statistical interpretation should keep the observation distinct from the inference. The observation is the count recorded in each dose arm. Inference would require a defined comparison, a method appropriate to the design and analysis population, and an account of uncertainty and missing information. Those pieces are not available in the registry record, so conclusions should remain descriptive.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("ARM 1", "ARM 2", "ARM 3", "ARM 4", "ARM 5")
n      <- c(2, 9, 7, 10, 7)
events <- c(2, 9, 6, 8, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  ARM 1  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  ARM 2  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7
ARM  ARM 3  7  6  85.7  42.1  99.6  48.7  97.4  47.3  96.8
ARM  ARM 4  10  8  80.0  44.4  97.5  49.0  94.3  48.2  94.0
ARM  ARM 5  7  6  85.7  42.1  99.6  48.7  97.4  47.3  96.8

11. Multiplicity, Missing Data and Analysis Populations

The record lists one primary outcome measure and no posted secondary outcome measures. It also lists no analyses. The outcome description concerns five Proellex doses and a placebo run-in, but no set of planned primary contrasts or testing hierarchy is reported in the registry record. It is therefore not possible to determine which comparisons were prespecified or whether any adjustment for multiple comparisons was planned or used.

As a general statistical matter, evaluating several dose groups can involve multiple comparisons. When many hypotheses are tested, the chance of obtaining at least one apparently noteworthy result can increase unless the analysis accounts for that multiplicity. Methods include defining a primary contrast in advance, using a testing hierarchy, or adjusting inference across comparisons. These are general options; the registry does not state that any particular approach was used. No p-values or inferential comparisons are posted for the primary outcome.

The endpoint is described for a per-protocol population requiring trough levels on at least 7 of the 10 weekly visits. The record does not report how many participants were eligible for that analysis, how many lacked outcome observations, or why any data were missing. It does not describe imputation, exclusion rules beyond the per-protocol definition, or sensitivity analyses. These missing-data procedures are not reported in the registry record.

Likewise, the registry does not report an intention-to-treat analysis, a separate safety analysis population, or a plan for handling participants who did not complete dosing or follow-up. The exact population contributing to each posted adverse-event summary is given through the at-risk counts, but the relationship between those counts and the primary endpoint population is not explained. The implications of missing data or analysis-population choices therefore cannot be quantified from the posted record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: breast cancer (8.3%).

The adverse-event record reports, by arm, the number at risk and the number affected by serious adverse events, as well as the number at risk and the number affected by other adverse events. For serious events, the posted figures are 0 of 12 in ARM 1, 0 of 10 in ARM 2, 1 of 12 in ARM 3, 0 of 12 in ARM 4, and 0 of 12 in ARM 5. For other adverse events, the corresponding affected counts are 8 of 12, 6 of 10, 7 of 12, 11 of 12, and 11 of 12. These are registry counts, not estimates adjusted for exposure duration or other factors.

The registry lists Breast cancer as the top serious adverse-event term, at 8.3%. It does not give arm-specific counts for that term in the registry entries, so the term should not be assigned to a particular arm or interpreted as a comparative rate. The death counts are not reported in the registry record.

Serious and other adverse-event summaries are distinct categories. The listed at-risk counts may differ from the primary endpoint denominators, and the record does not explain the relationship between the safety and efficacy analysis populations. The timing, duration, severity grading, causality assessment, and exposure-adjusted safety analyses are not reported in the registry record. Consequently, these figures describe reported affected-participant counts and should not be treated as a complete comparative safety analysis.

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

The primary results establish what the registry records for the per-protocol induction amenorrhea endpoint: participant counts in each of the five dose arms over the stated 10 weeks. The outcome definition includes suppression of ovulation and/or menses, assessed using ovulation timing kits and a daily diary for bleeding. The counts are useful as a descriptive account of participants meeting that definition in the listed groups.

They do not establish the magnitude or precision of a treatment effect. The record does not post a statistical comparison, confidence interval, or p-value, and it does not provide a separate placebo outcome count. Although the endpoint description refers to a placebo run-in, the listed outcome arms are the five Proellex doses. Thus, the primary results do not provide a direct numerical comparison with a placebo group.

The counts also do not establish that an observed pattern is caused by dose. Such an inference would depend on treatment allocation, the actual analysis population, the handling of missing data, and a statistical analysis appropriate to the design. The record identifies the study as randomized and single-blind, but does not report enough operational or analytical detail to assess those elements fully. The crossover model field and independent-groups wording in the endpoint description also leave the analysis structure unclear.

Nor do these primary endpoint counts provide a complete account of menstrual or ovulatory changes. They do not separately report participants with ovulation suppression, participants with menstrual suppression, duration of amenorrhea, or the timing of an outcome. These details are not reported in the registry record.

The adverse-event figures describe reported affected participants by arm, but they do not establish comparative safety. There are no exposure-adjusted rates, statistical comparisons, or details of event timing and attribution in the record. The registry summary should therefore be read as a limited description of recorded outcomes, not as a stand-alone basis for clinical decisions or a definitive judgment about benefit and harm.

14. Why This Trial Matters Statistically

This trial is statistically notable because it places a binary outcome across several dose arms while describing both a crossover model and an independent-groups comparison. These design features lead to different ways of analyzing data. In a crossover design, a participant may contribute observations under more than one condition, so within-participant dependence can matter. In an independent-groups design, outcomes are compared across separate groups. The registry does not resolve how the trial’s design was implemented or which analytical structure generated the posted counts.

The primary endpoint is also tied to a per-protocol criterion based on trough levels during dosing. That makes the definition of the analysis population especially relevant. A reader needs to know how many participants were represented, what happened to people who did not meet the criterion, and whether results were also analyzed according to original randomization. Those details are not reported in the registry record.

The five dose arms create a natural need to clarify which comparisons were intended to answer the primary question. As a general statistical issue, examining multiple doses can raise questions about multiplicity and interpretation. The record does not identify a primary dose contrast, testing hierarchy, or adjustment method, and it posts no inferential analyses. The numerical counts can be described, but they cannot be treated as evidence that one dose differs from another without a reported estimate and its uncertainty.

The study therefore illustrates why registry results need more than arm-level counts for a full statistical interpretation. Clear reporting of the analysis population, outcome rules, missing-data handling, design structure, and prespecified comparisons would help readers understand what the counts estimate and how stable the comparisons are. In their absence, the most defensible reading remains descriptive and bounded by the posted endpoint definition.

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 registry record leaves several trial-specific uncertainties. It labels the model crossover, but the primary outcome description refers to comparisons in independent groups and an escalating-dose approach. It does not report the treatment sequence, whether participants received more than one dose, or how period and carryover effects were addressed. Consequently, the structure of the primary analysis cannot be reconstructed from the record.

The primary endpoint is restricted to a per-protocol population requiring trough levels at specified visits. The registry does not report how that condition affected eligibility for analysis, how many participants were excluded from the primary analysis, or whether a broader analysis was performed. The listed enrollment should not be mistaken for the endpoint denominator.

The endpoint definition combines suppression of ovulation and/or menses. The record does not explain how these components were combined, how missing diary or kit data were treated, or how conflicting measurements were resolved. It also does not report outcome counts for a separate placebo group, despite the reference to a placebo run-in.

No primary outcome analysis is posted beyond the participant counts. Confidence intervals, p-values, model details, covariate adjustments, planned comparisons, and multiplicity procedures are not reported in the registry record. The adverse-event summary likewise lacks event timing, severity grading, attribution, and exposure-adjusted analyses. These gaps limit assessment of precision, comparative effects, and safety patterns.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Determination of the Lowest, Safe and Effective Dose of Proellex — NCT01187043.
• Registry record last updated 2014-07-28; status last verified 2014-06.
• Results first posted 2014-07-28.
• 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 lists NCT01187043 as a completed randomized, single-blind Phase I/II study of oral Proellex, with a crossover model and enrollment of 52. The study started in 2010-08 and reached primary completion in 2012-03. Its title describes a placebo run-in and comparison of five oral doses.

The primary endpoint is Induction Amenorrhea, measured as a participant count over 10 weeks. The outcome description refers to suppression of ovulation and/or menses, assessed using ovulation timing kits and a daily bleeding diary. The endpoint population is per protocol and requires trough levels on at least 7 of the 10 weekly visits. Counts are posted for the 1 mg, 3 mg, 6 mg, 9 mg, and 12 mg arms.

The record lists one outcome measure and no posted analyses or secondary outcome measures. It provides arm-level serious and other adverse-event counts, and lists Breast cancer at 8.3% as the top serious adverse-event term. Statistical comparisons, confidence intervals, missing-data methods, and fuller design and safety details are not reported in the registry record.