Dysport® Pediatric Lower Limb Spasticity Follow-on Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dysport® Pediatric Lower Limb Spasticity Follow-on Study (NCT01251380), a na phase 3 study. The primary outcome is Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period..

2. Clinical Question

3. Trial Design

This was a Phase III, prospective, multicentre, open-label extension study of repeated Dysport treatment. Its stated purpose was to assess long-term safety and efficacy in children with lower limb spasticity and dynamic equinus foot deformity due to cerebral palsy. The registry lists the study as completed and records enrollment of 216.

The study is classified as single-group, with allocation not applicable and masking absent. That design matters when interpreting the results: the extension does not provide a concurrent randomized control group against which to compare adverse events or changes in muscle tone and function. The primary outcome nevertheless refers to the double-blind plus open-label period. The available record does not give enough detail to reconstruct the earlier double-blind study or to treat it as a control comparison for the extension.

Dysport was injected into one or both lower limbs in up to 4 cycles. The registry describes intervals of at least 12 weeks and up to 40 weeks between cycles. Listed dose ranges varied by whether one or two legs were treated. The intervention description also states a maximum dose of no more than 30 U/Kg; the record text describing that limit is truncated, so further detail should not be inferred.

The registry lists 17 outcome measures, including the primary adverse-event count and secondary measures of muscle tone, physician global assessment, goal attainment, and ankle movement. It reports no outcome analyses. The record therefore supports a description of the design and the posted adverse-event counts, but not a detailed assessment of the efficacy outcomes or the methods used to analyse them.

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: Of 216 subjects enrolled in this open label study from Study Y-55-52120-141, 203 went straight into Cycle 1. 13 subjects were not considered eligible for re-treatment at end (all of whom had received Dysport) and as per study design they entered into the observational phase of Study 147. Of these 13, 4 subjects entered Cycle 1 at a later date.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population - all enrolled subjects. One subject received placebo in the DB study and two treatment cycles of Dysport in the OL study. However, as both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycle 1 and Treatment Cycle 2), the subject was excluded from the analysis (no TEAEs reported for this subject).

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 Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period., measured over From baseline (Day 1) until end of study (Week 40) of Cycle 1 and up to Week 28 of Cycles 2 to 4..

The primary endpoint counts participants with treatment-emergent adverse events reported during the double-blind plus open-label period. The registry describes adverse events as being monitored from informed consent to the end of the study, and says they were elicited through direct, non-leading questions or spontaneous reports. This endpoint is used to describe the occurrence of safety events during follow-up; it is a participant count, not a measure of how often events occurred or how long they lasted.

The posted safety results distinguish serious adverse events from other adverse events. The registry reports 7 participants with serious adverse events among 215 at risk, and 147 participants with other adverse events among 215 at risk. These categories should not be added to create a total, because the record does not state whether participants could appear in both categories. The primary outcome title refers broadly to treatment-emergent adverse events, but the registry record does not present a separate combined count for that endpoint.

Counting participants with events gives a practical summary of how many people experienced an event during the defined observation period. It does not by itself establish that treatment caused an event, compare risk with an untreated group, or describe the full clinical severity of all reported events. No confidence interval or formal analysis for the primary endpoint is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count tell the reader?

A count of participants with an event describes how many people in the stated analysis group experienced an event during the defined observation period. It is different from a count of all event occurrences: a participant may experience more than one event, but the participant count records that person as having an event. Counts are useful for a straightforward description of safety observations, but they do not describe event duration, recurrence, or timing unless those details are reported separately.

The registry reports participant counts and denominators for serious and other adverse events. It does not report a confidence interval or an inferential analysis for the primary endpoint. Without an analysis estimate and its uncertainty, the record does not quantify how precisely the observed counts represent a broader population. A confidence interval, in general, expresses a range of values compatible with an estimate under a statistical model. It is not reported for these endpoint results.

Why does the single-group design matter?

A randomized comparison can help distinguish differences associated with assigned treatments from differences that arise from participant characteristics or the course of illness. This extension is classified as single-group, with no masking and no applicable allocation. As a result, the adverse-event counts describe what was recorded among participants receiving study treatment, but do not provide a concurrent control rate. They cannot, on their own, establish whether an event was more or less common because of treatment.

The primary endpoint title spans a double-blind period and an open-label period, but the extension record does not provide a comparative analysis across those periods. Nor does it establish that results from the earlier study form a valid control for the extension. A comparison across periods would require details about eligibility, follow-up, exposure, and analysis that are not reported in the registry record.

How should serious and other events be read?

The posted safety data report serious and other adverse-event categories separately. The number of participants in each category is a count of affected people, not a rate per unit of follow-up. The registry does not specify whether the categories are mutually exclusive, so the counts cannot be combined into a total. It also does not report event-level totals, person-time, or a breakdown by treatment cycle.

The serious-event terms are accompanied by percentages in the registry. Those percentages should be read as the reported figures for the listed terms, not as newly calculated rates or as evidence of causality. The record does not state whether the percentages refer to participants or events in every case, how repeated events were handled, or whether the events were considered treatment-related.

What is missing from the analysis record?

The registry lists outcome measures but reports zero analyses. It does not report an inferential analysis plan, model specification, confidence intervals, p-values, or results for the secondary efficacy outcomes. The sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The record does not provide the underlying efficacy estimate or a trial-specific sample-size justification. Such planning illustrations are not observed power and do not substitute for an analysis of trial results.

In general, a confidence interval helps show the uncertainty around an estimate, while a statistical test addresses compatibility with a specified null hypothesis under its assumptions. Neither can be reconstructed responsibly without the relevant outcome estimates, analysis details, and participant-level or summary information. No new calculation is needed to describe the registry’s reported event counts, but further statistical conclusions would require information absent from the record.

Why might event counts need careful context?

Safety observations depend on the duration and completeness of follow-up, how events were elicited, and how events were classified. The registry gives an observation timeframe and describes questioning and spontaneous reports, but does not provide a detailed account of missing safety observations, adjudication, or exposure-adjusted analysis. In general, longer observation can create more opportunity to record an event; without comparable follow-up across groups, simple counts do not support comparative risk conclusions.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary adverse-event endpoint and secondary measures of muscle tone, physician global assessment, goal attainment, and ankle movement. It reports zero analyses. A plan for handling multiple outcomes or repeated assessments is not reported in the registry record. When several outcomes are assessed, multiplicity can increase the chance that apparently notable findings arise by chance; methods such as prespecifying a primary outcome or adjusting inference can address that issue in general. No such strategy should be attributed to this study without documentation.

Missing-data methods, rules for handling incomplete follow-up, and sensitivity analyses are not reported in the registry record. The study description gives observation timeframes for the primary endpoint, but does not state how participants with incomplete observation contributed to the endpoint. The adverse-event results provide denominators of 215 at risk, while the registry enrollment is 216. The complete explanation for that difference is not available in the record. Its population description mentions a participant whose treatment did not fall within specified dose ranges and includes an incomplete exclusion statement, so the exact analysis-population handling cannot be fully established from the text.

The primary endpoint description calls its population the safety population and says it includes all enrolled subjects, then gives the participant-specific caveat. Because that text is truncated, it is not possible to resolve the precise inclusion rule. No efficacy analysis population is reported. These gaps matter because both outcome multiplicity and analysis-population definitions affect how results should be interpreted. The registry record does not support assumptions about prespecified statistical procedures, missing-data imputation, interim analyses, or the handling of secondary outcomes.

11. 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: pneumonia (0.9%), adenoidal hypertrophy (0.5%), lymphadenopathy (0.5%), status epilepticus (0.5%), complex partial seizures (0.5%).

The safety results list 7 participants with serious adverse events among 215 at risk and 147 participants with other adverse events among 215 at risk. These are participant counts, not counts of all event occurrences. The record does not clarify whether a participant could be included in both categories, so the categories should not be added together.

The registry lists pneumonia at 0.9% among the serious adverse-event terms. Adenoidal hypertrophy, lymphadenopathy, status epilepticus, complex partial seizures, and partial seizures are each listed at 0.5%. These reported percentages identify terms appearing in the registry; the record does not provide enough information to determine the number of distinct participants for each term, whether repeated events occurred, or whether the terms were considered related to treatment.

The observation period is described as extending from baseline through the end of the study, with cycle-specific timeframes in the primary outcome definition. The record does not provide follow-up person-time or a comparison group. Accordingly, the counts characterize reported events during this study, but do not establish a comparative rate or a causal relationship to Dysport. The registry also does not report a confidence interval for these safety figures.

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

The posted results describe adverse events observed during a completed, open-label extension study of repeated Dysport treatment in children with cerebral palsy and dynamic equinus foot deformity. The registry reports serious and other adverse-event participant counts, as well as several serious-event terms and their associated percentages. These data provide a descriptive account of reported safety observations in the recorded study population.

They do not establish whether Dysport caused any reported event. The study has no concurrent randomized comparator, and the registry does not report a comparative analysis. The counts also do not establish that the event frequency would be the same in another group, under a different treatment schedule, or in a different population. Event occurrence can reflect multiple factors, and the available information does not separate those influences.

The registry’s stated purpose includes long-term safety and efficacy, but the reported results available in the record do not include analyses of the secondary efficacy measures. Those measures include muscle-tone scores, physician global assessment, goal attainment, and Tardieu Scale measures. Their names alone are not results: without reported estimates, uncertainty, and analysis details, the direction and magnitude of any change cannot be assessed.

The adverse-event categories also should not be treated as a single total, because the registry does not say whether the same participant could be counted in both. The difference between the enrollment figure and the safety denominator is not fully explained in the available text. The treatment eligibility caveat in the population description is truncated as well. These limitations restrict interpretation of the analysis group and the completeness of the safety summary.

In general, a result is most informative when the outcome definition, analysis population, comparison, and uncertainty are clear. Here, the record supports a limited descriptive reading of the posted counts. It does not support a conclusion about comparative safety, treatment causality, or efficacy.

13. Why This Trial Matters Statistically

This study illustrates an important distinction between monitoring safety and estimating a comparative treatment effect. An open-label extension can record adverse events during repeated treatment and follow participants over an extended study period. Those observations can be useful for describing what was reported in the enrolled group. Without a concurrent control group, however, the design cannot distinguish treatment-associated differences from background events or other changes over time.

The record also shows why an endpoint’s label and its posted results need to be read together. The primary endpoint is described as a count of participants with treatment-emergent adverse events across double-blind and open-label periods, while the posted safety figures separate serious and other events. The record does not give a distinct combined primary-endpoint count or clarify overlap between categories. A reader should not construct a total that the record does not define.

Another statistical issue is the separation between outcome registration and outcome reporting. The registry names several efficacy measures but reports no analyses for them. A prespecified outcome list can indicate what investigators intended to measure, but it does not reveal observed effects or their precision. Without those results, the efficacy part of the stated study purpose cannot be evaluated from the registry record.

Finally, the enrollment and safety denominators, together with the incomplete population description, demonstrate why analysis populations require clear documentation. Statistical interpretation depends not only on the outcome values but also on who was included and how incomplete data were handled. The record permits a careful description of reported safety counts, while leaving important design and analysis questions unresolved.

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.

The principal limitation for interpretation is the single-group, open-label design. There is no randomized comparator for the extension, so the observed adverse-event counts cannot establish comparative risk or treatment causation. The primary outcome refers to both double-blind and open-label periods, but the registry does not provide enough information to reconstruct a controlled comparison across those periods.

Reporting is incomplete for the outcomes central to efficacy. The registry lists secondary measures but reports no analyses or results for them. It also does not report confidence intervals, p-values, or a detailed statistical analysis plan. The absence of those details prevents assessment of the size and precision of any efficacy estimates and leaves the planned handling of multiple outcomes unclear.

The safety reporting is limited to participant counts and selected serious-event terms. The record does not state whether participants could contribute to both serious and other categories, give a breakdown by treatment cycle, or report exposure-adjusted event rates. It does not provide complete information on event relatedness, recurrence, or adjudication. These omissions restrict interpretation of the safety summary beyond its descriptive content.

There is also uncertainty about the analysis population. Enrollment is listed as 216, while 215 are at risk in the posted safety results. The population description refers to a participant who received placebo during the double-blind study and Dysport during the open-label study at doses outside stated ranges, but the exclusion text is incomplete. The record therefore does not fully establish how that participant was handled or how the denominators were formed.

Finally, details of missing-data handling and completeness of follow-up are not reported. The study’s specific population and treatment schedule also limit how far descriptive observations can be generalized. These limitations do not invalidate the recorded counts, but they constrain the conclusions that can be drawn from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dysport® Pediatric Lower Limb Spasticity Follow-on Study — NCT01251380.
• Registry record last updated 2022-09-28; status last verified 2022-09.
• Results first posted 2017-06-01.
• 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

NCT01251380 is a completed Phase III prospective, multicentre, open-label extension study sponsored by Ipsen. It evaluated repeated Dysport treatment for lower limb spasticity in children with dynamic equinus foot deformity due to cerebral palsy. The registry lists a single-group design, no masking, and enrollment of 216.

Treatment involved injections into one or both lower limbs over up to 4 cycles, with cycle intervals from 12 to 40 weeks. The primary outcome was the number of participants with treatment-emergent adverse events across the double-blind and open-label periods. The safety results report 7 participants with serious adverse events and 147 with other adverse events, each among 215 at risk.

The registry lists secondary measures of muscle tone, physician assessment, goal attainment, and ankle movement, but reports zero analyses. The record does not provide efficacy results, a comparative analysis, or a complete explanation of the safety population.