Compound 31543 (Calcitriol, USP) in Patients Receiving Taxane-based Chemotherapy Regimens for the Treatment of Chemotherapy-Induced Alopecia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Compound 31543 (Calcitriol, USP) in Patients Receiving Taxane-based Chemotherapy Regimens for the Treatment of Chemotherapy-Induced Alopecia (NCT01588522), a non-randomized phase 1 study. The primary outcome is Dose-limiting Toxicities (DLT) of Topical Compound 31543.

2. Clinical Question

The study was designed to evaluate safety, tolerability and pharmacokinetics of topical Compound 31543 in adults receiving taxane-based chemotherapy. The registry summary also identifies hair loss during treatment as a question of interest. The recorded primary endpoint focuses more narrowly on dose-limiting toxicities (DLTs): clinically significant Grade 3 or 4 non-hematologic toxicities during the first 28-day cycle that investigators considered possibly, probably or definitely related to Compound 31543 and not the chemotherapy regimen.

The record lists six concentration levels and describes topical application to the scalp. The summary says participants were to apply the treatment twice daily, beginning at least 5 days before chemotherapy, for at least 3 months or until chemotherapy was completed. It also describes blood sampling and photographic assessment of hair at specified follow-up visits, alongside a hair-condition diary. These planned assessments indicate that the study considered systemic exposure and hair outcomes as well as safety. The registry record does not report results for those outcomes, so their observed values and patterns cannot be described.

3. Trial Design

This was a Phase I, non-randomized, unmasked, sequential study. Its official title identifies it as a dose-escalation study of topical Compound 31543 in adult cancer patients receiving taxane-based chemotherapy. The registry lists six concentrations: 5, 10, 20, 40, 60 and 80 μg/mL. Enrollment was 28, and the study status is completed. The registry record lists a start date of 2012-09-17 and primary completion date of 2017-02-16.

Because allocation was non-randomized and the design was sequential, concentration groups should not be interpreted as randomized treatment arms. Participants were not assigned by chance to a concurrent control group, and masking was absent. Differences between groups, if calculated elsewhere, could reflect factors other than concentration, including participant characteristics, treatment sequence or chance. The record does not describe a separate comparator receiving no topical treatment or another topical product.

The intervention descriptions specify topical application of 0.25 mL to each of the four scalp quadrants twice daily. They also describe a pre-treatment period of 2 weeks, or 7 ± 2 days if a participant was unable or unwilling to undergo 2 weeks of pretreatment. The brief summary describes starting at least 5 days before chemotherapy and continuing for at least 3 months or until chemotherapy was completed. These entries give different levels of detail about the schedule; a complete reconciliation is not reported in the registry record.

The stated monitoring included blood draws at weeks 1, 5, 9, 13 and 54, and hair photographs before treatment and at weeks 7, 15, 27 and 54. Participants were also to keep a diary about hair condition. The primary endpoint was DLTs during the first 28-day treatment cycle; secondary outcomes include blood concentration and photographic review measures. The registry record does not report a sample-size justification, detailed dose-escalation rules, stopping rules or a complete statistical analysis plan.

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: Patients scheduled to receive follow up treatment with a taxane-based chemotherapy regimen

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Consisted of all patients who received at least one application of Compound 31543.

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: Safety Population: Received at least 1 dose of Compound 31543 Calcitriol

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Dose-limiting Toxicities (DLT) of Topical Compound 31543, measured over 28 days.

The primary endpoint counts participants with a dose-limiting toxicity during the first 28-day treatment cycle. The registry defines a DLT as clinically significant Grade 3 or 4 non-hematologic toxicity occurring in that cycle, judged by investigators to be possibly, probably or definitely related to Compound 31543 and not to the taxane-based regimen. Toxicities were graded according to CTCAE v4.0. The endpoint population includes patients who received at least one application of Compound 31543.

A participant count is a direct way to describe how many treated participants met the study’s specified toxicity definition. In an early-phase dose-escalation study, safety and tolerability are central concerns because the study is evaluating exposures across concentration levels. The endpoint definition also makes clear that attribution mattered: investigators were asked to distinguish events considered related to the topical compound from events attributed to chemotherapy. That judgment is inherently different from merely recording that a medical problem occurred.

The endpoint is narrower than all adverse events. It excludes hematologic toxicity and focuses on specified severe grades, timing and investigator-assessed relationship. The registry record does not report the observed number of participants meeting this DLT definition, nor does it provide uncertainty estimates or a comparison of DLT counts across concentration levels. Therefore, the endpoint’s planned meaning can be described, but its observed result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a sequential, non-randomized Phase I dose-escalation study. That design label matters for interpreting any group-level numbers: the concentration groups were not formed through random allocation, and there was no masked treatment assignment. General statistical interpretation should therefore remain descriptive. A difference in counts across dose groups cannot by itself isolate a concentration effect, because concentration and the order or circumstances of enrollment may be entangled with other participant or study factors.

What does a participant count describe?

The primary endpoint is a count of participants who satisfy a defined DLT rule. A participant count is distinct from a count of all events. One participant may have more than one event, while a participant-level endpoint records whether the participant meets the definition. The registry’s primary endpoint specifies severity grade, toxicity type, time window and investigator-assessed attribution. Each part affects which participants qualify. A count of serious adverse events or other adverse events cannot be assumed to equal the count meeting the DLT definition.

Counts are most informative when their denominators and analysis populations are clear. The record says the DLT population consisted of all patients who received at least one application, but it does not report the primary endpoint numerator. The adverse-event entries separately report numbers at risk and numbers affected in concentration groups. Those group figures should be read in their stated terms and not substituted for the endpoint population or for an unreported DLT result.

Why is non-randomized dose escalation important?

In a randomized comparison, random allocation is intended to balance measured and unmeasured participant characteristics across groups on average. This study is explicitly non-randomized, so that protection does not apply. Sequential enrollment can also mean that later concentration groups are observed under different calendar or operational circumstances from earlier groups. The registry record does not describe these circumstances or provide adjustments for them. As a result, simple comparisons among concentrations are descriptive and do not establish that concentration caused any differences in outcomes.

The absence of masking also matters. Participants and study personnel knew the treatment assignment, according to the registry. This can influence subjective assessments, reporting or investigator attribution, although the record does not establish that such influence occurred. The DLT definition relies in part on an investigator’s judgment about whether toxicity was related to the topical compound rather than the chemotherapy regimen. That attribution should therefore be distinguished from an objective count of all recorded medical problems.

How should uncertainty be considered?

General statistical principle: a confidence interval describes a range of values compatible with the data under a specified method and assumptions. It helps readers assess precision, rather than treating an observed estimate as exact. Small group counts generally permit limited precision, and a count alone does not show how uncertain an underlying event frequency may be. No confidence intervals for the DLT endpoint are reported in the registry record, and no DLT estimate is reported to which an interval could be attached.

General statistical principle: a zero observed count does not prove that the underlying risk is zero. The amount of information depends on the number of participants observed, the follow-up and the event definition. Here, the registry lists 0 deaths in each group, but those entries do not establish the absence of all possible mortality risk, nor do they speak to nonfatal toxicity. They are descriptive counts within this study record.

What can the secondary outcomes contribute?

The listed secondary outcomes cover pharmacokinetic measures, including Week 1 Day 1 concentrations, Cmax and AUC0-t, and pre-dose concentrations at later visits. The record also lists top-view and right-side photographic review scores. Pharmacokinetic measures describe drug exposure in blood; photographic scores are assessments of hair appearance. These outcomes address distinct questions and require outcome-specific analysis. The registry record does not report their results, analysis methods or uncertainty estimates.

General statistical principle: repeated measurements from the same participant are related, rather than independent observations. Analysis of measurements over time often needs to account for that within-participant correlation. The planned blood draws and photographs occur at multiple visits, but the statistical approach for repeated measurements is not reported in the registry record. No particular model or method should be assumed.

What does the sample-size illustration mean?

Any planning illustration based on an observed effect is not the trial’s own sample-size justification. Such an illustration describes hypothetical participant numbers under stated assumptions, not the number needed to guarantee a result and not “observed power.” The registry record does not report the study’s sample-size rationale or design assumptions. Since the primary DLT effect is not reported, the illustration cannot serve as evidence about the observed safety outcome. It should remain separate from the trial’s actual enrollment and from any claim about the precision of its findings.

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("Compound 31543 Calcitriol - 5 μg/mL", "Compound 31543 Calcitriol - 10 μg/mL", "Compound 31543 Calcitriol - 20 μg/mL", "Compound 31543 Calcitriol - 40 μg/mL", "Compound 31543 Calcitriol - 60 μg/mL", "Compound 31543 Calcitriol - 80 μg/mL")
n      <- c(3, 3, 6, 4, 4, 3)
events <- c(0, 0, 0, 0, 0, 0)
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  Compound 31543 Calcitriol - 5 μg/mL  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Compound 31543 Calcitriol - 10 μg/mL  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Compound 31543 Calcitriol - 20 μg/mL  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Compound 31543 Calcitriol - 40 μg/mL  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Compound 31543 Calcitriol - 60 μg/mL  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Compound 31543 Calcitriol - 80 μg/mL  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures, including the primary DLT endpoint, pharmacokinetic measurements and photographic hair-review scores. Considering several outcomes creates a multiplicity issue in general: the more questions tested, the greater the chance of at least one apparently notable result arising by chance if each is interpreted without regard to the broader set. Whether that concern is material depends on the analysis plan and intended role of each outcome. The registry record does not report a multiplicity strategy, such as a hierarchy of outcomes or adjustment of statistical tests.

The record does not report inferential analyses, and it lists zero analyses. It therefore does not show which outcomes were analyzed, whether any analyses were planned but not posted, or whether a prespecified statistical testing approach was followed. The statistical analysis plan is not reported in the registry record. No interim analyses or stopping rules are reported there either, so none should be inferred from the dose-escalation design.

Missing-data handling is also not reported in the registry record. The study summary describes measurements at several follow-up visits, but does not say how missed visits, incomplete photographs, unavailable blood samples or early discontinuation were handled. It does not state whether analyses used observed measurements only, imputed values or another approach. These choices can affect interpretation when outcome availability differs across participants or over time.

The primary endpoint population is described as patients who received at least one application, but the record does not give the number analyzed for that endpoint or explain how participants without a complete 28-day assessment were treated. Enrollment of 28 does not by itself establish the analysis denominator. Without outcome-specific denominators, missing-data methods and analysis details, readers cannot assess whether the reported adverse-event counts or any unreported outcome estimates represent all enrolled participants or a subset.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (50.0%), supraventicular tachycardia (33.3%), muscular weakness (33.3%), pain (33.3%), pyrexia (33.3%).

The serious adverse-event entries report the number of participants at risk and the number affected within each concentration group. The counts affected are 0 of 3 at 5 μg/mL, 1 of 3 at 10 μg/mL, 1 of 6 at 20 μg/mL, 4 of 4 at 40 μg/mL, 1 of 4 at 60 μg/mL and 2 of 3 at 80 μg/mL. Deaths are listed as 0 in every group. These figures are descriptive; the study was not randomized, and the groups are not like-for-like controls.

The registry also reports participants affected by other adverse events: 3 of 3, 3 of 3, 6 of 6, 4 of 4, 3 of 4 and 3 of 3, in concentration order. “Affected” indicates participant counts in the record and should not be read as a count of separate event episodes. The entries do not establish severity, duration, causality or whether events met the primary DLT definition.

The registry lists serious-event terms with percentages, including Abdominal Pain (50.0%) and several terms listed as 33.3%. The denominator and method behind those percentages are not explained in the registry record. They should not be interpreted as directly comparable participant risks without that information. The adverse-event summaries do not report the DLT endpoint result.

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

The record describes a completed Phase I study of topical Compound 31543 in adults receiving taxane-based chemotherapy, with a planned focus on safety, tolerability and pharmacokinetics. It identifies six concentration levels and gives adverse-event counts by group. It also specifies a primary DLT definition based on toxicity grade, type, timing and investigator attribution. These details clarify what the investigators intended to evaluate.

The record does not report the observed primary endpoint result. It therefore cannot show how many participants had a DLT under the stated definition. Nor does it report results for the listed pharmacokinetic outcomes or photographic hair-review scores. The adverse-event counts provide descriptive safety information, but they do not answer whether an event was a DLT, whether it was attributable to the topical compound, or whether concentration caused a difference.

The non-randomized, sequential design does not support a direct causal comparison across concentration groups. The groups are not randomized controls, and no comparative analysis is reported. The listed counts should not be interpreted as proof that one concentration is safer or less safe than another. The record also does not establish whether hair loss differed with treatment or whether blood exposure followed a particular pattern.

More broadly, the absence of posted analyses and uncertainty estimates limits conclusions about precision. A participant count is a description of the observed record, not a complete estimate of future event risk. The fact that the study is marked completed does not mean that all outcome results are posted. The statistical record supports describing the design and its available safety counts; it does not support a treatment-effect conclusion or a definitive account of the primary safety endpoint.

14. Why This Trial Matters Statistically

This study raises several statistical issues that commonly arise in early-phase clinical research. First, a dose-escalation design asks safety questions across concentration levels, but sequential non-random allocation does not create balanced comparison groups. Group counts can help describe what was observed at each level, yet they should not be treated as randomized evidence of a concentration-response relationship.

Second, endpoint definitions matter. The primary endpoint is not simply “any adverse event.” It is a participant-level DLT count restricted by toxicity grade, non-hematologic classification, a defined treatment-cycle window and investigator-assessed causal attribution. The record separately reports serious and other adverse events. Keeping these concepts distinct is essential to avoid treating broad safety summaries as if they answered the prespecified primary question.

Third, the record illustrates why reporting results and denominators is necessary for interpretation. Enrollment is stated, and adverse-event group counts are listed, but the primary DLT result and analyses are absent. Without the outcome numerator, analysis population and uncertainty estimates, readers cannot judge the precision of the main safety endpoint. Secondary pharmacokinetic and hair-assessment outcomes are also listed without reported values.

Finally, planning calculations and observed results answer different questions. A sample-size illustration based on an observed effect is not evidence of observed power and does not replace the study’s own design justification. The registry record does not report that justification. These distinctions help keep an early-phase descriptive study in its proper statistical frame: informative about its questions and recorded events, but not a randomized comparative test.

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 available registry information has important study-specific limitations. The trial was non-randomized, unmasked and sequential, with no like-for-like control group. Comparisons across concentration levels therefore cannot isolate the effect of concentration from differences in participants, enrollment sequence or other study circumstances. The registry record does not report adjusted comparative analyses.

The primary endpoint result is not reported, despite the detailed DLT definition. The record lists adverse-event counts, but does not say which events met that definition or provide the investigator’s attribution for the primary analysis. It also does not report the outcome-specific denominators, confidence intervals or other precision measures for the primary endpoint. The serious-event term percentages are listed without an explanation of their denominator.

The study enrolled 28 participants, while the adverse-event entries give group-specific numbers at risk. The record does not explain the relationship between these numbers and enrollment, or give a participant flow showing how many completed treatment or follow-up. The analysis populations for secondary outcomes are not reported. This is particularly relevant for the planned blood sampling and photographic reviews at repeated visits, because completeness at each visit is not described.

The registry contains some differences in schedule detail: the summary describes treatment beginning at least 5 days before chemotherapy and continuing for at least 3 months or until chemotherapy was completed, while the arm descriptions include a pre-treatment period of 2 weeks or 7 ± 2 days in specified circumstances. The complete schedule is not reconciled in the registry record. Dose-escalation rules, sample-size justification, statistical analysis methods, missing-data handling and multiplicity procedures are also not reported. No results for the listed pharmacokinetic or hair-assessment outcomes are available in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Compound 31543 (Calcitriol, USP) in Patients Receiving Taxane-based Chemotherapy Regimens for the Treatment of Chemotherapy-Induced Alopecia — NCT01588522.
• Registry record last updated 2026-08-17; status last verified 2026-04.
• Results first posted 2025-05-28.
• 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

NCT01588522 is a completed, non-randomized, unmasked, sequential Phase I study sponsored by BPGbio. It enrolled 28 adults with cancer receiving taxane-based chemotherapy and evaluated topical Compound 31543 (calcitriol) across concentration levels of 5, 10, 20, 40, 60 and 80 μg/mL. The stated primary endpoint was the participant count with a defined DLT during the first 28-day treatment cycle.

The registry reports adverse-event counts by concentration group and lists serious-event terms. It does not report the primary DLT result, analyses, or numerical results for the listed pharmacokinetic and photographic hair-review outcomes. The non-randomized sequential design does not provide randomized, like-for-like comparisons among concentrations. The record also does not report the statistical analysis plan, missing-data approach, multiplicity strategy or sample-size justification.