Dysport in Vulvodynia Phase II Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dysport in Vulvodynia Phase II Study (NCT03598777), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the DB Treatment Period (Stage 1).

2. Clinical Question

The study was designed to define Dysport doses and evaluate efficacy and safety compared with placebo. Its primary endpoint, however, concerns safety: the number of participants with treatment-emergent adverse events (TEAEs) during Stage 1's double-blind treatment period. The reported safety population includes randomized participants who received at least one administration of investigational medicinal product, including partial administration.

The registry record describes a dose-escalation stage followed by a dose-expansion stage. It states that one or two doses selected from Stage 1 would be investigated further in Stage 2, depending on Stage 1 results. The posted primary endpoint results are for Stage 1 and are counts of participants, not a direct measure of symptom change or treatment effect on vulvodynia. Although secondary outcomes listed in the record include pain and dilator-related measures, their results are not reported in the registry record.

The registry record does not report additional details about participant characteristics or eligibility criteria. Therefore, the population to which the posted counts apply is described by the study condition and safety-population definition, rather than by a fuller clinical profile.

3. Trial Design

This was a Phase II, randomized, double-blind, placebo-controlled study with a sequential model and planned dose escalation and dose expansion. The registry record lists enrollment of 60 and identifies the study condition as vulvodynia. It records a start date of 2018-06-11, primary completion on 2021-01-21, and a terminated status. The reason for termination is not reported in the registry record.

Both stages were described as having a double-blind period with treatment cycle 1, followed by an open-label treatment period. Stage 1 was the dose-escalation stage. The listed Dysport groups were 100 U, 300 U, 400 U and 500 U, alongside placebo. The arm descriptions state that Dysport was injected intramuscularly on day 1 of each cycle, while placebo was injected on day 1 of cycle 1. In Stage 2, one or two doses selected from Stage 1 were to be further investigated; the record does not identify which dose or doses were selected.

The primary safety endpoint pertains specifically to the Stage 1 double-blind period, from baseline at Cycle 1 Day 1 through Cycle 1 Week 12. The posted safety groups are placebo and the four listed Dysport doses. The study's design includes later open-label treatment, but the primary endpoint is not described as covering that period.

Randomization and double-blinding are stated design features. The randomization method, allocation ratio, concealment procedures and details of who was masked are not reported in the registry record. Nor does the record give further information about the dose-escalation rules, the transition from Stage 1 to Stage 2, or the criteria used to select doses. Those details should not be inferred from the sequential design label or the arm descriptions.

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: For each participant, the study consisted of a DB treatment period (Cycle 1; participants received Dysport or placebo) followed by a follow-up period and/or open-label (OL) treatment period (Cycles 2 to 4; participants received Dysport). A total of 60 participants were randomised and received treatment with placebo or Dysport in the DB treatment period for Stage 1. Up to a maximum of 800 Units (U) Dysport was planned but 500 U was the maximum dose tested due to early study termination.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety population included all randomised participants who received at least one IMP administration (including only partial administration).

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All randomised participants were included in the baseline analysis.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the DB Treatment Period (Stage 1), measured over From Baseline (Cycle 1 Day 1) to Cycle 1 Week 12 (DB treatment period, Stage 1).

The primary endpoint counts participants who experienced at least one treatment-emergent adverse event (TEAE) during the Stage 1 double-blind treatment period. The timeframe runs from baseline, defined as Cycle 1 Day 1, to Cycle 1 Week 12. Results are expressed as participant counts in each specified category, rather than as a continuous measurement or an average change.

The registry record defines a TEAE as an event with a start date on or after the first investigational medicinal product administration. An adverse event can be an undesirable medical condition or deterioration of a pre-existing condition after or during exposure; it may include symptoms, signs or abnormal investigation results. The event need not be considered causally related to the study product to meet the adverse-event definition. Investigators assessed relatedness to treatment.

For a safety endpoint, counting participants with at least one event provides a way to describe how many people had an event during the specified observation period. It does not count every event when a participant has more than one, and the count alone does not establish whether an event was caused by treatment. The record also identifies events of special interest, including possible remote spread of toxin effect, urinary or faecal incontinence, and potential hypersensitivity reactions. The posted primary endpoint figures do not supply a causal assessment or a detailed account of event types for each participant.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with matching each number to its endpoint, population and observation window. In this study, the primary endpoint is a participant count for TEAEs during the Stage 1 double-blind treatment period. The safety population comprises randomized participants who received at least one investigational medicinal product administration, including partial administration. The timeframe starts at Cycle 1 Day 1 and ends at Cycle 1 Week 12. Counts should therefore be read as applying to that population and period, not automatically to every enrolled participant or to later open-label treatment.

What does a participant count represent?

A count of participants with at least one event describes how many people met the endpoint definition. It is different from a count of all adverse-event episodes: one person with multiple events still contributes as one participant to a measure defined by participants affected. The registry provides at-risk and affected counts by group. Those figures permit a straightforward descriptive reading of the recorded outcomes. They do not, on their own, provide an adjusted treatment comparison or a measure of statistical uncertainty.

The adverse-event definition also matters. A TEAE is based on its start date relative to the first study-product administration, and the registry definition does not require that the investigator judge it related to treatment. Relatedness was assessed separately. Thus, a TEAE count should not be translated into a count of events caused by the investigational product. Serious adverse events are a distinct category from the broader TEAE endpoint, so the serious-event counts and other adverse-event counts answer different descriptive questions.

What can randomization and masking contribute?

In general, random assignment is intended to reduce systematic differences between comparison groups at the point of assignment. Blinding is intended to limit the influence of treatment knowledge on participants' experiences, care or outcome assessment. These are general principles, not evidence that all sources of bias were eliminated in this particular study. The registry identifies randomized allocation and double masking, but does not report the randomization procedure, allocation concealment or masking details. No additional implementation claims can be made from the record.

The trial is described as sequential, with dose escalation followed by dose expansion. This explains the broad structure, but not the rules used to escalate doses, pause enrollment or select doses for further investigation. The protocol-level decision rules and any statistical methods for dose selection are not reported in the registry record. In general, dose-finding designs can use accumulating safety and efficacy information to guide later study stages; the specific method used cannot be inferred from the design label.

How should uncertainty and comparisons be understood?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method. Its width reflects precision: less precise estimates tend to have wider intervals. A p-value, when reported, summarizes how unusual data at least as extreme as those observed would be under a specified null model. Neither is a substitute for interpreting the endpoint definition, study design and clinical context. The registry record has no posted analyses for the primary endpoint, and it reports no confidence intervals or p-values for the group counts. Consequently, no inferential comparison should be read into the descriptive figures.

The sample-size assumptions described for the planning illustration are two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. This is a planning illustration based on an observed effect, not the trial's own design justification. Sample-size illustrations describe hypothetical planning requirements under their assumptions; they are not observed power and do not establish what the completed study was designed to detect. The trial's own sample-size justification is not reported in the registry record.

In general, over-dispersion describes more variability in data than a chosen statistical model expects. When present, it can make uncertainty estimates too narrow if the extra variability is ignored. That concern is relevant to some count-data analyses, but the posted primary results are participant counts by group and no statistical model or dispersion estimate is reported. It would be inappropriate to claim that over-dispersion was present or that a particular model was used.

The outcome list contains several pain-related measures and time points, including changes in pain ratings, threshold-based participant counts, and dilator-related outcomes. Multiple outcomes and time points can raise multiplicity concerns: when many statistical tests are performed, the chance of at least one apparently notable result can increase. In general, a prespecified testing strategy can address how results are interpreted across outcomes. The registry record does not report a multiplicity adjustment or a detailed testing hierarchy, and the secondary outcome results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including mean changes in vaginal dilator-induced pain and other dilator-related measures, as well as counts of participants meeting specified improvement thresholds. Some outcomes are listed at more than one time point. When many outcomes or time points are tested, multiplicity can make isolated findings harder to interpret because the overall chance of a false-positive result may increase. In general, trial protocols can address this with a prespecified hierarchy or an adjustment method. Such a strategy is not reported in the registry record.

The primary endpoint is a safety count, and the record does not report a statistical analysis plan for comparing groups on that endpoint. It also lists no posted analyses. There are no reported confidence intervals or p-values for the primary outcome. The presence of group counts therefore should not be mistaken for a formal hypothesis test or for evidence that a particular multiplicity approach was used.

The record defines a safety population as randomized participants who received at least one investigational medicinal product administration, including partial administration. It does not report the numbers excluded from that population, the handling of participants with incomplete observations, or how missing safety information was addressed. The analysis population for the listed efficacy outcomes is not reported in the registry record. Missing-data methods, imputation procedures and sensitivity analyses are also not reported.

These omissions limit assessment of how outcomes were analyzed and how robust any comparisons might be. They do not show that a particular method was or was not used; they mean that the methods are not reported in the registry record. The posted results are best read as descriptive safety counts for the stated Stage 1 period and population.

11. 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 non-serious adverse event terms

The serious adverse event counts are zero for placebo and for each listed Dysport dose. The corresponding numbers at risk are 13 for placebo, 8 for Dysport 100 U, 8 for Dysport 300 U, 14 for Dysport 400 U and 17 for Dysport 500 U. A zero observed count means no participant in that group was recorded with a serious adverse event during the reported period; it does not establish that such events could not occur.

The registry also reports participants affected in the other adverse-event grouping: 1 in the placebo group, 3 in the Dysport 100 U group, 3 in the Dysport 300 U group, 3 in the Dysport 400 U group and 6 in the Dysport 500 U group. These counts should be read alongside their respective at-risk counts, and as participants rather than total event episodes. They do not identify whether an event was considered related to treatment.

In general, serious and other adverse-event categories are not interchangeable. The serious-event figures address the serious category, while the broader TEAE endpoint includes events meeting the timing definition whether or not they were judged treatment-related. The registry does not list serious event terms for these groups. Small group counts and the lack of inferential analyses mean that the figures are descriptive and do not support a precise comparative safety estimate.

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

The registry record gives a focused description of Stage 1 safety during the double-blind treatment period. It reports participants with serious adverse events and participants in the other adverse-event grouping, together with the numbers at risk in the placebo and four Dysport dose groups. Those counts describe what was recorded in the defined safety population and timeframe.

The counts do not establish that an event was caused by a study product. The TEAE definition is based on the timing of event onset relative to first administration, while treatment relatedness was assessed separately. The record does not provide a group-level causal assessment alongside the counts. Nor do the figures by themselves show that differences between groups are statistically reliable or clinically important.

The absence of serious adverse events in the posted groups is a statement about the observed counts, not proof that serious events are impossible or that no safety concern exists. Conversely, counts in the other adverse-event grouping do not alone establish a treatment effect. The registry does not report inferential comparisons, confidence intervals or a detailed event-level account that would support a more complete interpretation.

The study was designed to evaluate efficacy and safety and includes secondary outcomes concerning pain and vaginal dilator measures. Results for those secondary outcomes are not reported in the registry record. Consequently, the posted safety counts do not answer whether Dysport changed pain outcomes, and they do not establish an overall benefit-harm balance. The registry record reports that the study was terminated but does not state why; termination status should not be treated as an outcome or interpreted as evidence about efficacy or safety.

In general, clinical interpretation depends on the endpoint, the population, the observation period, precision and study conduct. Here, the reported counts are informative as a record of observed events in specified groups, but the absence of efficacy results and inferential safety analyses leaves substantial questions unanswered.

13. Why This Trial Matters Statistically

This study is statistically notable for combining a sequential dose-escalation and dose-expansion structure with a randomized, double-blind, placebo-controlled design. Dose-finding studies pose a different question from a simple two-group comparison: later dose selection depends on information gathered earlier. The registry describes that overall structure, while leaving the decision rules and analysis methods unreported. Distinguishing the stated design from unreported operational details is important when interpreting what the record can establish.

The posted primary endpoint is safety-focused and defined as participants with TEAEs over a specified Stage 1 double-blind period. That clear time window and participant-based measure help frame the counts. At the same time, the record lists several pain-related secondary outcomes and multiple assessment times. This combination highlights a recurring statistical issue: a study can collect many kinds of outcomes, while the interpretation depends on knowing which were primary, how comparisons were planned, and how missing observations were handled.

Randomization and double-blinding are meaningful design features, but they do not replace reporting of the statistical analysis plan or analysis results. Without inferential comparisons, uncertainty estimates and efficacy outcome results, the posted data remain descriptive. The record also illustrates why registry status and completion dates should be separated from outcome interpretation: the study is marked terminated, but the reason is not reported.

For clinical researchers and biostatisticians, the central lesson is to align interpretation with the reported estimand, population and time window. Here, the safety counts can be described precisely as recorded, while broader conclusions about comparative safety, dose selection or efficacy require information that is not reported in the registry record.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific details needed for a fuller interpretation are not reported in the registry record. The reason for the terminated status is not stated. The dose-escalation rules, criteria for choosing doses for Stage 2, and the doses selected for expansion are also not identified. The record's sequential-design label and brief stage descriptions do not supply those decision details.

The registry identifies randomization and double masking but does not describe the randomization method, allocation concealment or masking procedures. It does not report a detailed statistical analysis plan, the trial's own sample-size justification, or methods for handling missing data. The safety population is defined, but the record does not describe exclusions from that population or give further details on incomplete safety observations.

Although multiple secondary outcomes are listed, their results are not reported in the registry record. No analyses are posted, and no confidence intervals or p-values accompany the primary safety counts. The registry also does not report a multiplicity strategy or a detailed account of adverse-event terms by group. These gaps prevent assessment of inferential precision, robustness to missingness, or the planned interpretation across endpoints.

The reported safety counts concern the Stage 1 double-blind treatment period and should not be generalized to the later open-label period, for which these primary endpoint figures are not described. The listed groups are modest in size, and the count data are descriptive; no additional comparative estimate should be inferred from them. The limitations concern what the registry record reports and do not establish that unreported procedures were absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dysport in Vulvodynia Phase II Study — NCT03598777.
• Registry record last updated 2021-12-09; status last verified 2021-10.
• Results first posted 2021-12-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes NCT03598777, a Phase II randomized, double-blind, placebo-controlled study of Dysport in vulvodynia. Its sequential design included a dose-escalation stage and a dose-expansion stage, with double-blind treatment followed by open-label treatment in both stages. Enrollment is listed as 60. The study started on 2018-06-11, had primary completion on 2021-01-21, and is marked terminated; the reason for termination is not reported in the registry record.

The primary endpoint was the number of participants with TEAEs during the Stage 1 double-blind period, from Cycle 1 Day 1 through Cycle 1 Week 12. The posted results give at-risk and affected participant counts for placebo and Dysport 100 U, 300 U, 400 U and 500 U. No analyses are posted, and results for the listed pain-related secondary outcomes are not reported in the registry record. The record therefore supports descriptive interpretation of the specified safety counts, rather than inferential conclusions about comparative effects.