Dysport® Adult Upper Limb Spasticity Extension Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dysport® Adult Upper Limb Spasticity Extension Study (NCT01313312), a na phase 3 study. The primary outcome is Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs).

2. Clinical Question

This clinical question is principally descriptive: what adverse events were recorded among participants who received repeated treatment during the extension? The record also lists changes in muscle tone measured with the Modified Ashworth Scale, including the overall primary targeted muscle group and specific muscle groups at Week 4. Those secondary measures address different questions from the primary safety outcome. They do not turn the study into a comparative efficacy trial, because no concurrent control group is listed.

3. Trial Design

This is a Phase III, multicentre, prospective, open-label extension study. The registry lists the study as completed, with a single-group model, no masking, and allocation recorded as NA. Enrollment is listed as 258. In the treatment description, 254 participants received at least one open-label injection and contributed to the safety analysis population described in the primary outcome record.

The intervention was intramuscular botulinum toxin type A, named as Dysport®. The record says participants received between 1 and 5 injections according to individual needs, over a period of up to 12 months. It also states that an appropriate dosage of 1000 Units [U] or 500 U was administered on Day 1 of treatment. The primary safety timeframe extends up to Week 52. The registry record does not report further detail about how individual treatment decisions were made or how later doses were selected.

An open-label, single-group extension can document what happened among participants treated in the study, including adverse events and recorded changes in outcomes over time. It cannot by itself estimate a treatment effect relative to an untreated or alternative-treatment group. Without random allocation and a concurrent comparator, differences over time may reflect factors other than treatment, including the course of the underlying condition, other care, measurement variability, or who remained available for follow-up. These are general interpretive considerations, not findings about the participants in this study.

The registry describes the purpose as assessing long-term safety over repeated treatment cycles. The primary outcome is treatment-emergent adverse events, while the listed secondary outcomes include Modified Ashworth Scale changes and proportions with specified grade reductions. The registry record lists 41 outcome measures and 0 analyses. Detailed protocol information, including a sample-size justification, is not reported in the registry record.

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 227 subjects who completed Study 145, 4 subjects entered an observational phase and never received treatment with Dysport® in this open label extension study (Study 148). The remaining 223 subjects were eligible for retreatment and progressed to Study 148. In addition, 31 of the 34 de novo subjects screened were included in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.

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: Baseline characteristics are reported for the 254 Subjects who entered this open label study (223 from Study 145 and 31 de novo subjects) and received at least one open label injection of Dysport®.

6. Primary Endpoint

The registry lists the primary outcome as Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs), measured over Up to Week 52.

The primary endpoint is the assessment of long-term safety through collection of treatment-emergent adverse events (TEAEs) up to Week 52. The record defines a TEAE as an event that started or worsened in severity during the treatment phase after the participant received study medication. The measure is expressed as the number of participants, so the posted counts describe participants with events rather than a modeled treatment effect.

The endpoint also distinguishes adverse events of special interest (AESIs), defined as events assessed as due to remote spread of effect of Dysport® or as hypersensitivity reactions. The primary outcome description says TEAEs, AESIs, severe TEAEs, serious adverse events (SAEs), treatment-related TEAEs, TEAEs leading to withdrawal, and fatal SAEs are summarized by treatment cycle. The registry record does not provide all of those category-specific results in the registry record for this account.

Safety endpoints are used to characterize unwanted events observed during treatment and follow-up. Counting participants with an event can be informative for describing the burden of events in the study population, but the count alone does not establish that treatment caused an event. That distinction matters especially in an extension study without a concurrent comparator, where background events and events related to participants’ underlying conditions may also occur. The registry record does not report an analysis that separates those explanations.

The outcome population is described as participants who entered the study and received at least one open-label injection. Only participants with data available for analysis at the point of testing are reported. That qualification is important when reading any endpoint count: the number available may depend on the outcome and the time at which it was assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several features determine what can be learned statistically from this study: it has one treatment group, it is open label, its main outcome is a count of participants with safety events, and the registry limits reporting to participants with data available at each point of testing. These features shape interpretation independently of whether a particular event is important clinically.

What does a single-group design estimate?

A single-group study can describe outcomes among participants who received the intervention. For a safety endpoint, a count of participants with an event gives a direct summary of what was recorded in that treated group. It does not estimate the difference between treatment and control, because no control-group result is available. A descriptive count can be useful for documenting events, but it cannot separate treatment-related risk from background event occurrence or other explanations.

Random allocation in a comparative trial is intended to make groups comparable, on average, with respect to measured and unmeasured factors. This study is not recorded as randomized and has no concurrent control group, so that protection against confounding is absent. The record does not report a causal analysis that would address this limitation. Comparisons with results from other studies would also need caution because differences in populations, follow-up, event definitions, and reporting can affect the observed counts.

What does open-label mean for measurement?

Open-label means treatment masking is listed as none. Participants and study personnel were not masked to the treatment in the way a blinded design would aim to conceal assignment. For an objectively defined event, awareness does not necessarily determine whether it occurred, but it can influence reporting, assessment, attribution, or decisions to investigate and record an event. This is a general possibility, not evidence that reporting was biased in this trial. The registry record does not report procedures intended to assess or correct such effects.

How should event counts be understood?

The primary outcome uses participants as its unit and describes the number with events. A participant count is different from a count of all event episodes: a participant can experience more than one event, while a count of participants records whether a participant had an event in the relevant category. The kind of measure recorded for this outcome is participants with an event. The posted figures therefore should not be reinterpreted as numbers of event episodes unless the registry explicitly says so.

In general, a confidence interval describes the range of values reasonably compatible with the observed data under a specified statistical procedure and its assumptions. It communicates uncertainty as well as the point estimate. No confidence interval for the primary safety counts is included in the registry record for this account, and no interval should be inferred from the counts alone. A p-value, when used in a suitable comparative analysis, addresses compatibility with a null hypothesis under a model; it does not measure the probability that a treatment caused an event. The registry record does not report a comparative test for the primary safety outcome.

Why do the analysis population and timing matter?

The safety population is described as participants who entered the study and received at least one open-label injection. The outcome description also says that only participants with data available at the point of testing are reported. This means the denominator for an assessment can depend on who has usable data at that time. Missing outcome data can affect a result if availability is related to participants’ health, treatment exposure, or outcomes. The registry entries do not describe the amount or pattern of missing data by assessment, or any imputation procedure.

Follow-up extending up to Week 52 raises a general distinction between a fixed-time participant count and an analysis that accounts for different lengths of observation. A participant observed for less time has less opportunity for an event to be recorded than a participant observed for longer. Time-to-event methods can address unequal follow-up under their assumptions, but the registry entries do not establish that such a method was used for these safety results. The primary measure is described as a number of participants, and no time-to-event analysis is listed in the registry record.

What is over-dispersion, and does it apply?

Over-dispersion is a general feature of some count-data models: the observed variability is greater than the model’s assumed variability. It can arise when events cluster within participants or when people differ in their underlying event rates. A model that ignores over-dispersion may give uncertainty estimates that are too narrow. The primary outcome is expressed as participants with an event, rather than a reported count of repeated event episodes, and the registry record does not report a count model or a dispersion assessment. Over-dispersion therefore should not be assumed to have been analyzed.

How should planning illustrations be read?

Any sample-size planning illustration based on an observed effect is a planning scenario, not observed power and not evidence that the trial was designed around that effect. General planning calculations depend on assumptions such as the significance level, allocation, statistical approximation, and effect size chosen for detection. The study record says the illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event calculations, the description refers to a total number of events; for other calculations, it refers to participants per arm. These assumptions describe an illustration rather than this single-group study’s allocation. The registry record does not report the trial’s own sample-size justification, and no planning values are included in the registry record for this account.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 41 outcome measures and 0 analyses. The primary safety outcome is identifiable, and several secondary outcomes are named, including Modified Ashworth Scale changes and proportions with specified grade reductions. A long list of outcomes can raise a multiplicity concern: when many outcomes are tested, the chance of at least one apparently notable result can increase. Statistical plans may address this through a prespecified hierarchy, adjustment, or a clear distinction between primary and exploratory outcomes. The registry record does not report whether any multiplicity procedure was specified or used. The secondary measures should therefore not be treated as confirmatory findings on the basis of the outcome list alone.

Missing-data information is limited. The primary outcome description states that only participants with data available at the point of testing are reported. It does not specify the number missing for each outcome or time point, why data were unavailable, or whether the analysis used imputation or another missing-data method. In general, missingness can affect interpretation when participants with unavailable data differ systematically from those with observed data. The registry entries do not establish whether that occurred in this study.

The safety population is defined as participants who entered the study and received at least one open-label injection. The registry lists enrollment of 258 and describes 254 participants receiving injections. It does not report why those figures differ or give a full accounting of participants by analysis population. The outcome-specific availability of data may also affect denominators at individual assessments. A full protocol, statistical analysis plan, and detailed disposition of participants are not reported in the registry record, so the handling of these issues cannot be assessed further.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: epilepsy (0.8%), urinary retention (0.8%), haematoma (0.4%), adenocarcinoma pancreas (0.4%), prostate cancer (0.4%).

The Total Dysport® group lists 21 participants with serious adverse events among 254 at risk. It lists 142 participants with other adverse events among 254 at risk. These are participant counts, not counts of every event episode, and the two categories should not be assumed to be mutually exclusive. The registry record does not provide enough detail in the registry record to determine whether an individual participant appears in both categories.

The listed serious-event terms include Epilepsy and Urinary retention at 0.8% each, and Haematoma, Adenocarcinoma pancreas, Prostate cancer, and Device malfunction at 0.4% each. Those percentages are presented as reported; they are not evidence of causation. The primary outcome distinguishes treatment-emergent events from events assessed as treatment-related, and those categories are not interchangeable. The registry entries do not provide a causal assessment for each listed serious-event term.

Deaths are not reported in the registry record. The record describes safety assessment through Week 52 and says adverse events are summarized by treatment cycle, but cycle-specific results are not included in the registry record. In general, safety counts are most informative when read with their definitions, observation periods, denominators, and completeness of follow-up. Those details do not make a single-group count a comparative risk estimate.

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

The results describe safety events recorded in a single group of participants treated with Dysport® in an open-label extension study. The listed counts indicate that serious adverse events and other adverse events were recorded among participants in the safety population. The serious-event terms and percentages identify events reported in the registry; they do not establish that Dysport® caused those events. Nor do the counts compare the experience of treated participants with what would have occurred under another treatment or without treatment.

The study’s design makes its primary contribution descriptive. Repeated treatment and follow-up up to Week 52 allow the record to address events observed during an extension period, but the registry entries do not establish a treatment-attributable risk or a comparative benefit. Because there is no concurrent comparator, the event counts cannot distinguish treatment effects from background occurrence, participants’ underlying conditions, or other influences. This limitation remains even when an event is assessed as treatment-emergent: timing after treatment is part of the event definition, not proof of cause.

The registry also identifies Modified Ashworth Scale outcomes as secondary measures. The outcome names show that the study assessed changes in muscle tone and specified grade reductions at Week 4, but numerical results for those outcomes are not included in the registry record for this account. Their magnitude, variability, and precision therefore cannot be described. An outcome being listed in the registry is not equivalent to a reported result.

The record lists 258 enrolled participants and 254 participants who received at least one injection and were included in the safety population description. The reason for the difference is not reported in the registry record. The primary outcome further notes that only participants with available data at each testing point are reported, so the number contributing information may vary by measure and time. Missing-data details are not reported.

In general, statistical interpretation separates what was observed from what can be inferred. The observed counts can characterize events in this study population. A comparative claim, a causal claim, or a conclusion about the precision of an effect would require additional design or analysis information that is not reported in the registry record. The results should be read within those limits rather than as a definitive estimate of treatment effect.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of what an open-label extension can and cannot contribute. A single-group study can describe events during repeated exposure and can record outcomes over an extended treatment period. Such descriptive evidence is distinct from a randomized comparison, which is designed to estimate differences between groups while reducing confounding through allocation. Recognizing that distinction prevents safety counts from being interpreted as comparative risks.

The registry record also illustrates why endpoint definitions matter. A TEAE is defined by when an event began or worsened in relation to receipt of study medication. AESIs have an additional description based on assessment of remote spread of effect or hypersensitivity. These definitions specify how events are categorized; they do not make all categories equivalent or settle whether a particular event was caused by treatment. Clear interpretation depends on keeping timing, severity, seriousness, and attribution distinct.

Another statistical issue is the relationship between follow-up and available data. The study describes treatment over up to 12 months and a primary safety timeframe up to Week 52, while reporting only participants with data available at the point of testing. Results can be difficult to interpret if denominators vary over time and the reasons for missing observations are unknown. The registry record does not provide a detailed account of missingness or its statistical handling.

Finally, the record lists many outcome measures but no analyses. That contrast is a reminder that a registered outcome is a statement of what was to be assessed, not evidence of a particular result. Reporting the analysis population, outcome-specific denominators, uncertainty intervals, and analysis methods would support a fuller appraisal. The registry entries do not include those details for all outcomes, so the soundest reading remains descriptive and tied to the results that are explicitly reported.

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 most important design limitation is the absence of a concurrent comparator. The registry classifies the study as single-group, with no masking and allocation recorded as NA. Results can describe events in participants who received Dysport®, but cannot estimate a difference against another treatment or a control condition. The open-label design may also affect event reporting or assessment in general, although the registry entries do not show that it did so in this study.

The enrollment count and safety population are not identical: the registry lists 258 enrolled and describes 254 participants receiving at least one injection for safety analysis. The reason is not reported in the registry record. The primary outcome description further limits reporting to participants with data available at each point of testing. Outcome-specific denominators, the extent and reasons for missing data, and any method for handling missing observations are not reported in the registry record.

Although the primary outcome description says safety events are summarized by treatment cycle, cycle-specific numerical results are not included in the registry record for this account. The registry also lists 41 outcome measures and 0 analyses. Numerical results for the listed secondary Modified Ashworth Scale outcomes are not reported in the registry record, so their observed effects and precision cannot be evaluated. Confidence intervals and inferential analyses for the primary safety counts are also not reported in the registry record.

The registry record does not report the trial’s sample-size justification, detailed statistical analysis plan, multiplicity procedures, or a full participant disposition. It also does not provide further detail about the event-level context for the serious adverse events. These gaps limit assessment of how completely the posted results represent the planned analyses and how sensitive interpretations may be to missing data or analysis choices.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dysport® Adult Upper Limb Spasticity Extension Study — NCT01313312.
• Registry record last updated 2022-09-28; status last verified 2022-09.
• Results first posted 2017-06-07.
• 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

NCT01313312 is a completed Phase III, multicentre, prospective, open-label extension study of Dysport® for upper limb spasticity in adults with spastic hemiparesis due to stroke or traumatic brain injury. It is recorded as a single-group study with no masking and allocation listed as NA. Enrollment is 258; the safety population description covers 254 participants who received at least one open-label injection.

Participants received between 1 and 5 intramuscular injections according to individual needs, over up to 12 months. The primary outcome assesses treatment-emergent adverse events through Week 52. The registry lists 21 participants with serious adverse events and 142 with other adverse events, each among 254 at risk. Modified Ashworth Scale outcomes are listed as secondary measures, but numerical results for them are not included in the registry record.

The study provides descriptive safety information without a concurrent comparator. Detailed missing-data handling, the sample-size justification, and a full statistical analysis plan are not reported in the registry record.