Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1 (NCT02124083), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Tolerabilty of 200 mg Vorinostat in Niemann-Pick Disease, Type C1.

2. Clinical Question

This is a safety- and tolerability-focused question in a small, single-group study, rather than a comparative treatment-effect question. Completion of the 200 mg phase is a practical tolerability measure: it records whether participants reached the end of that dose period. Completion alone does not establish why a participant did or did not complete treatment, and it does not substitute for a detailed account of adverse events, dose changes, or clinical outcomes.

The record identifies Niemann-Pick disease type C1 as the target condition and names vorinostat as the intervention. It describes the study as phase 1/2 and records its status as completed. The registry record does not provide a primary outcome count, a comparison group, or a treatment-effect estimate. Therefore, the posted information can describe the study question and some safety counts, but it cannot resolve whether the drug changed the disease course or biochemical markers.

3. Trial Design

The registry record describes a phase 1/2, non-randomized, open-label, single-center study of vorinostat in Niemann-Pick disease type C1. Allocation is listed as NA, masking as none, and the model as single group. The recorded enrollment is 12. The study status is completed, with a start date of 2014-04-25 and a primary completion date of 2016-12-13.

The intervention description gives an oral regimen of 200 mg daily for 3 months, followed by escalation to 400 mg daily for 3 months, with treatment scheduled 3 days on and 4 days off. The registry summary says participants would be evaluated at 0, 3 and 6 months. The primary outcome is the number of participants completing the 3-month 200 mg phase; its stated population is all participants who started the study.

The design has no parallel control group. The dose sequence is part of the intervention plan and should not be interpreted as a randomized comparison between dose groups. Without a separate group receiving another intervention or no study drug, changes over time cannot be separated from other influences using a direct controlled contrast. Open-label status also means masking was absent, although the record does not specify how that might have affected individual outcome assessments.

The registry summary identifies safety and tolerability as the primary objective and biochemical efficacy as a secondary objective. It mentions NPC1 protein expression and lipid and protein biomarkers, while the listed secondary outcomes include serum cathepsin D and serum LGALS3. The record does not provide the full protocol, the detailed assessment procedures, or a statistical analysis plan. It also does not report the count completing the primary phase or numerical results for the biochemical outcomes.

The enrollment and safety denominators describe the size of the recorded study and the participants at risk in the posted safety summary. They do not establish how many completed each dose phase. The primary endpoint’s outcome count is not reported in the registry record, so completion at 200 mg cannot be inferred from enrollment or from the safety denominators.

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: All participants who started 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Tolerabilty of 200 mg Vorinostat in Niemann-Pick Disease, Type C1, measured over 3 months.

The primary endpoint is the number of participants with tolerability of 200 mg vorinostat, operationalized in the registry description as the number of Niemann-Pick disease type C1 patients completing the 3-month 200 mg phase. The stated timeframe is 3 months, and the stated population is all participants who started the study.

Completion is used as a pragmatic summary of whether participants remained on the initial dose phase through its specified end. In a safety-focused early-phase study, this can indicate whether the regimen was feasible enough for participants to reach the planned phase endpoint. It is not a complete safety profile: participants who complete treatment may still experience adverse events, and non-completion can have reasons other than adverse events. The registry record does not specify how tolerability was defined beyond completion, or how discontinuations, interruptions, and dose modifications were handled.

The posted record does not include the number completing the 200 mg phase. It therefore does not provide the observed primary endpoint result. The adverse-event counts are separate safety summaries and cannot be used to reconstruct the completion outcome. Nor does a completion count, on its own, measure improvement in symptoms, disease progression, or biochemical markers. Those questions require their own outcome definitions and reported results, which are not available in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a single-group, non-randomized study with no masking. Those design features determine what statistical comparisons can be made. The posted information supports descriptive summaries of outcomes within the treated group, but it does not support a randomized between-group treatment contrast. A statistical method cannot create a control comparison that the study design did not include.

What does a single-group design show?

In general, a single-group study records outcomes among participants receiving the intervention. It can describe observed completion, adverse events, and biomarker measurements, if those results are reported. It cannot by itself distinguish intervention effects from changes that might also occur over time, differences among participants, or other influences. The record does not report a concurrent control group, a randomized allocation procedure, or a masked comparison.

The study describes a sequence from 200 mg to 400 mg, but this is not a parallel randomized dose comparison. Participants were initially dosed at 200 mg and the description then specifies escalation to 400 mg. Any changes observed later in the sequence could reflect the dose, elapsed time, continued participation, or other factors. The record does not report an analysis designed to separate those possibilities.

How should the primary endpoint be understood?

The primary outcome is a count of participants completing the 3-month 200 mg phase. A count is a direct descriptive summary, and its interpretation depends on a clear denominator and outcome definition. The registry names the population as all participants who started the study, but it does not provide the completion count or detailed rules for handling interruptions, withdrawal, or missing completion status. Therefore, the primary result cannot be reproduced or interpreted further from the posted record.

Completion is related to tolerability but is not identical to an adverse-event measure. A participant could complete the phase while experiencing an adverse event, or not complete for a reason unrelated to an adverse event. The registry does not describe the decision rules linking adverse events to dose changes or discontinuation. This distinction matters when reading the completion endpoint alongside safety counts.

Why are adverse-event counts descriptive?

The safety information reports counts of participants at risk and affected, together with percentages for listed serious-event terms. These summaries describe what was recorded in the treated group. Without a control group, the counts do not estimate an excess risk attributable to vorinostat. Without event timing, duration, severity grading, and attribution details, they also do not characterize the full clinical context for each event.

In general, adverse-event summaries can use either participant counts or event counts. Participant counts indicate how many people experienced at least one event of a specified type; event counts can include repeated occurrences in the same person. The registry’s safety fields give affected-participant counts for broad categories, while the term-level reporting does not explain its precise counting method or denominator. The percentages should therefore be quoted as recorded rather than reverse-engineered into counts.

What statistical uncertainty is available?

The registry record does not report an estimate with a confidence interval, a hypothesis test, or a statistical analysis result for the primary endpoint. A confidence interval, in general, expresses uncertainty around an estimate under specified assumptions. It helps distinguish a comparatively precise estimate from one that is compatible with a broad range of values. No interval can be described for the completion outcome because its result is not reported.

The record lists no analyses. This does not establish what analyses may have been conducted outside the registry; it means analysis results are not reported in the registry record. The statistical plan, including any prespecified models, handling of repeated measurements, and criteria for interpreting biomarker changes, is not reported in the registry record.

How do the biomarker outcomes fit?

The summary describes biochemical objectives related to NPC1 protein expression and lipid and protein biomarkers. The listed secondary outcomes include serum cathepsin D and serum LGALS3. The record does not give numerical values, variability measures, or analysis methods for these outcomes. General statistical interpretation of repeated biomarker measurements would depend on details such as measurement timing, within-participant correlation, missing samples, and the planned model; those details are not reported in the registry record.

In general, repeated measures from the same participant are correlated rather than independent. A method that accounts for this correlation can produce more appropriate uncertainty estimates than treating every measurement as unrelated. The registry record does not describe which approach, if any, was used. The posted information consequently does not support reconstruction of a biomarker analysis or an estimate of biochemical change.

What should sample-size illustrations mean?

Any sample-size planning illustration associated with the posted results is a hypothetical calculation based on an observed effect and stated assumptions, not an observed trial outcome. Such illustrations do not show that the study had a particular probability of detecting an effect, and they are not observed power. The record does not report the trial’s own sample-size justification or the assumptions used to plan enrollment. Any interpretation of planning calculations should remain separate from the study’s descriptive safety results and from the unreported primary endpoint.

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("Vorinostat")
n      <- c(12)
events <- c(12)
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  Vorinostat  12  12  100.0  73.5  100.0  75.8  100.0  75.3  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary biochemical outcome labels, including serum cathepsin D and serum LGALS3, with labels repeated in the outcome listing. It does not report how many hypotheses were formally tested, whether outcomes were grouped into families, or whether any adjustment for multiple testing was planned. A multiplicity strategy is not reported in the registry record.

In general, testing multiple outcomes can increase the chance that an apparently notable result arises by chance. Methods for addressing this include prespecifying a primary outcome, controlling error across a defined family of tests, or treating secondary findings as exploratory. The appropriate approach depends on the analysis plan and the purpose of the outcomes. Since neither test results nor the statistical plan are reported, no conclusion about adjustment or confirmatory status can be drawn from the record.

Missing-data methods are also not reported in the registry record. The primary endpoint is defined for all participants who started the study, but the record does not state how missing completion status was handled. It does not describe the amount or pattern of missing data for biochemical assessments, whether measurements were available at each planned evaluation, or whether any imputation or other missing-data approach was used.

Analysis populations beyond the stated primary outcome population are not reported in the registry record. The record does not specify whether biochemical analyses included all enrolled participants, only participants with available measurements, or another population. It also does not give a protocol-defined intention-to-treat or per-protocol approach. These omissions matter because the set of participants included in an analysis can affect both the estimate and its interpretation. The reported safety denominators should not be assumed to apply to every endpoint or analysis population.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cerebrospinal fluid leakage (16.7%), vomiting (8.3%), epstein-barr viraemia (8.3%), pyrexia (8.3%), liver function test increased (8.3%).

The registry safety summary lists 12 participants at risk and 5 affected for serious adverse events. For other adverse events, it lists 12 at risk and 11 affected. The record lists 0 deaths. These figures are descriptive counts; they are not a comparison with an untreated group and do not establish causation.

The reported serious-event terms are cerebrospinal fluid leakage, 16.7%; vomiting, 8.3%; Epstein-Barr viraemia, 8.3%; pyrexia, 8.3%; liver function test increased, 8.3%; and pneumonia aspiration, 8.3%. The record does not describe the event-level timing, severity grading, duration, or attribution for these terms. It does not explain whether the listed percentages use the same denominator or whether terms represent participants or events. They should therefore be read as reported, without converting them to counts or adding them together.

Seriousness and severity are distinct concepts in safety reporting: seriousness generally refers to regulatory or clinical consequences, while severity describes intensity. This is a general distinction; the record does not provide severity grades. The safety counts also do not indicate whether events occurred during the 200 mg phase, the 400 mg phase, or another period. The primary completion count is not reported, so these adverse-event summaries cannot establish how many participants completed the initial dose phase.

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

The record documents a completed phase 1/2, open-label, single-group study of vorinostat in Niemann-Pick disease type C1. Its primary objective was safety and tolerability, with completion of the 3-month 200 mg phase specified as the primary outcome. The record also lists biochemical objectives and adverse-event summaries. Those elements describe the study’s questions and the information posted, but they do not amount to a controlled estimate of treatment effect.

The safety summary reports serious and other adverse-event counts, including 0 deaths. The listed event terms and percentages give some description of reported safety experience. They do not establish whether events were caused by the drug, how their timing related to dose exposure, or how the observed experience compares with what would have occurred without treatment. There is no comparator group in the registry design.

The primary completion result is not reported in the registry record. Numerical biochemical outcome results are also not reported. Consequently, the posted record does not show whether the primary tolerability criterion was met, whether participants completed the planned dose sequence, or whether biomarkers changed. It does not support conclusions about effects on symptoms, disease progression, or clinical outcomes.

In general, a small early-phase study can provide descriptive experience useful for planning further research, but precision and generalizability depend on the data and design. Here, the statistical analysis results, uncertainty estimates, and detailed analysis plan are not reported. The record should therefore be interpreted as a limited registry summary, not as proof for or against a clinical benefit. It is also not possible to use the safety counts alone to rank the risks of different doses, because dose-specific event results are not reported.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary question is operationalized as phase completion rather than a direct measure of disease change. Completion is an interpretable feasibility and tolerability outcome, but it does not capture every aspect of safety and does not establish biochemical or clinical benefit. Separating the endpoint’s definition from broader claims about treatment is central to a careful reading.

The design also illustrates the limits of inference in an open-label, single-group study. Descriptive counts can summarize what happened among treated participants, but a control group is ordinarily needed for a direct comparison of outcomes under alternative treatment conditions. Without that comparison, observed events and changes over time cannot be attributed to the intervention through a randomized contrast.

The record contains safety counts but does not report the primary completion result, biochemical outcome values, uncertainty intervals, or analysis results. This gap highlights why registry outcomes and posted results need to be read together: knowing an endpoint was prespecified is not the same as knowing its observed value or precision. It also demonstrates why event counts, percentages, and completion outcomes answer different questions and should not be substituted for one another.

Finally, the study offers a setting in which early-phase and secondary biomarker aims coexist. Statistical interpretation would depend on a prespecified plan for repeated measurements, missing data, and multiple outcomes. Those methods are not reported in the registry record. Recognizing what is documented and what remains unavailable is an essential part of evaluating the strength of a clinical-trial result.

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 does not report the number of participants completing the 200 mg phase, despite defining that count as the primary endpoint. It therefore does not provide the primary outcome result needed to assess the stated completion-based tolerability measure. The safety counts cannot fill this gap because adverse events and endpoint completion are distinct outcomes.

The study is described as non-randomized, open-label, single-center, and single-group. There is no parallel control group for comparison. The design therefore does not provide a randomized estimate of how outcomes differ under vorinostat versus another treatment or no treatment. The sequential 200 mg and 400 mg regimen is not a randomized dose comparison, and dose-specific safety results are not reported.

Although the record gives counts for serious and other adverse events, it does not provide event-level timing, duration, severity grading, or attribution. The denominator and counting method for each serious-event term percentage are not explained. These omissions limit interpretation of the event profile and its relationship to dose or treatment period.

Numerical results for the listed biochemical outcomes are not reported in the registry record. The statistical analysis plan, uncertainty estimates, missing-data methods, multiplicity approach, and detailed analysis populations are also not reported. The record does not describe the eligibility criteria or additional participant characteristics needed to assess how closely the study population represents a broader clinical population. These limitations concern the available registry information and do not establish what may have been recorded elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1 — NCT02124083.
• Registry record last updated 2018-02-22; status last verified 2018-01-13.
• Results first posted 2018-02-22.
• 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.

19. Record Summary

The registry record describes a completed phase 1/2 study of vorinostat for Niemann-Pick disease type C1. It lists enrollment of 12 and characterizes the design as non-randomized, open-label, single-center, and single-group. The recorded treatment schedule was 200 mg daily for 3 months followed by planned escalation to 400 mg daily for 3 months, with 3 days on and 4 days off.

The primary outcome was the number of participants completing the 3-month 200 mg phase. Its result is not reported in the registry record. Safety information lists 5 affected participants among 12 at risk for serious adverse events, 11 among 12 for other adverse events, and 0 deaths. The record also lists serum cathepsin D and serum LGALS3 among secondary outcomes, but numerical biochemical results and statistical analysis results are not reported.