This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Long-term Open-label Study of Botulinumtoxin Type A to Treat Spasticity of Leg(s) or Leg(s) and Arm in Cerebral Palsy (NCT01905683), a na phase 3 study. The primary outcome is Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01905683 |
| Phase | Phase 3 |
| Condition | Lower Limb and Combined Lower Limb and Upper Limb Spasticity Due to Cerebral Palsy |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 370 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merz Pharmaceuticals GmbH |
| Results posted | Yes |
2. Clinical Question
Population
Children and adolescents age 2–17 years with cerebral palsy and spasticity affecting the lower limb or both upper and lower limbs. The registry describes 370 participants as treated at least once.
Intervention
IncobotulinumtoxinA, listed as 16–20 Units per kg body weight, administered by injection. The record describes treatment to muscles of the leg or legs, or the legs and one arm.
Comparator
There was no control group. The study is listed as single-group, open-label, and non-controlled, so the registry record does not describe a randomized comparison.
Primary question
How many participants experienced treatment-emergent adverse events overall and during each injection cycle, from the first injection through the end-of-study visit?
The clinical question is principally about long-term safety and tolerability in the enrolled population. The primary endpoint counts participants affected by treatment-emergent adverse events, rather than measuring the number of events or comparing event rates between treatment groups. The timeframe extends from the first injection to an end-of-study visit scheduled in the Week 50–66 range.
The registry also names secondary assessments covering tolerability, changes in plantar-flexor spasticity, impressions of change from investigators and families, pain, and gross motor function. These outcomes describe additional aspects of treatment experience and clinical status, but the numerical results for them are not reported in the registry record. The study question should therefore be distinguished from what can be concluded from the posted figures: the recorded adverse-event counts describe participants in the treated group, but without a comparator they cannot establish how those counts would differ under another treatment or no treatment.
3. Trial Design
This was a Phase 3, single-group, open-label, non-controlled study sponsored by Merz Pharmaceuticals GmbH. The registry lists enrollment of 370 participants and describes the study as completed. The listed start was 2013-08, and primary completion was 2017-01. The treatment was incobotulinumtoxinA at 16–20 Units per kg body weight.
Because the study had one treatment group and no control group, it was not designed as a randomized, like-for-like comparison of treatment strategies. The open-label design also means that treatment masking was absent. These design features matter when interpreting outcomes that involve judgment or reporting, such as impressions of change, pain, or adverse events. They do not invalidate the recorded observations, but they limit what those observations can establish about comparative effects.
The primary endpoint is the number of participants affected by treatment-emergent adverse events from the first injection through the end-of-study visit, described as Week 50–66. The registry identifies the safety-evaluable set as participants treated with the investigational product at least once. The listed treated population and the adverse-event risk set each include 370 participants.
The registry record does not report the rationale for the planned enrollment, detailed treatment-cycle scheduling beyond the outcome timepoints, or the statistical analysis plan. It also does not report interim analyses. The available description names multiple secondary outcomes, including assessments at specified points within injection cycles, but detailed numerical results for those outcomes are not reported in the registry record. Consequently, the design can be described from the registry, while details of the intended statistical procedures cannot be inferred.
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: A total of 391 participants were screened, of which 370 participants were enrolled and treated. Of these, 124 participants were recruited from the lead-in study (62, 29 and 33 participants from the IncobotulinumtoxinA high, mid and low dose group respectively of study MRZ60201\_3070\_1 \[2012-005054-30\]) and 246 participants were newly recruited.
Overall Study
| Stage | 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) |
|---|---|
| STARTED | 370 |
| COMPLETED | 319 |
| NOT COMPLETED | 51 |
Reasons for not completing this period:
| Reason | 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) |
|---|---|
| Protocol Violation | 1 |
| Re-injection criteria not met; others | 13 |
| Physician Decision | 1 |
| Lack of Efficacy | 8 |
| Withdrawal by Subject | 20 |
| Adverse Event | 4 |
| Lost to Follow-up | 4 |
Analysis population for the primary outcome, as defined in the registry: The SES was the subset of all participants treated with IP at least once.
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: The safety evaluation set (SES) was the subset of all participants treated with investigational product (IP) at least once.
| Characteristic | Unit | 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) |
|---|---|---|
| Participants analysed | 370 | |
| Age, Continuous | years | 6.2 (SD 4.1) |
| Age, Customized: Children (2-11 years) | Participants | 317 |
| Age, Customized: Adolescents (12-17 years) | Participants | 53 |
| Sex: Female, Male: Female | Participants | 150 |
| Sex: Female, Male: Male | Participants | 220 |
| Region of Enrollment: Austria | participants | 1 |
| Region of Enrollment: South Korea | participants | 59 |
| Region of Enrollment: Romania | participants | 22 |
| Region of Enrollment: Turkey | participants | 5 |
| Region of Enrollment: Czechia | participants | 1 |
| Region of Enrollment: Ukraine | participants | 170 |
| Region of Enrollment: Poland | participants | 67 |
| Region of Enrollment: Israel | participants | 1 |
| Region of Enrollment: Slovakia | participants | 5 |
| Region of Enrollment: Germany | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle, measured over From the timepoint of first injection up to end of study visit (Week 50-66).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who experienced treatment-emergent adverse events. The registry defines the observation period as beginning at the first injection and continuing through the end-of-study visit, which falls in the Week 50–66 range. It also says that values refer to the number of participants affected. Thus, the endpoint is a participant count, not a count of every event occurrence or a measure of event duration.
Counting affected participants is a useful way to describe how many people in the treated group had an event during follow-up. The endpoint is stated overall and per injection cycle, allowing the registry’s intended safety description to cover both the full observation period and individual cycles. However, cycle-specific counts are not reported in the registry record, so those patterns cannot be described from the recorded figures.
General: adverse-event monitoring is used to characterize events observed during treatment and follow-up. A count alone does not establish that treatment caused an event. It also does not show severity, timing, recurrence, or the clinical importance of every event unless those details are separately defined and reported. The endpoint is therefore a descriptive safety measure, not a controlled estimate of treatment effect. The registry’s description of the safety-evaluable set—participants who received the investigational product at least once—clarifies who was included in the stated safety population.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry lists 370 participants in the treatment group and a risk set of 370 for both serious and other adverse events. It reports 16 participants affected by serious adverse events and 20 affected by other adverse events. Deaths are reported as 0. These are participant counts in the treated group; they are not comparisons against a control group.
The listed serious adverse-event terms include Gastroenteritis (0.8%), Tenotomy (0.5%), Epilepsy (0.5%), Bronchitis (0.5%), Cast application (0.3%), and Arrhythmia (0.3%). These terms and percentages are presented as the leading serious-event terms in the registry record. They do not, on their own, show whether an event was considered related to treatment, when it occurred, whether a participant experienced more than one event, or how the registry selected the terms for listing. Those details are not reported in the registry record.
The counts describe events recorded during the study’s defined observation period. They are not evidence of a causal effect, because there is no comparison group to help distinguish events associated with treatment from events that might also occur in this population over time. The open-label design is another consideration for outcomes that depend on recognition or reporting. The findings are most directly read as a safety description of participants treated in this study, not as a comparative estimate.
The registry’s primary endpoint refers to treatment-emergent adverse events overall and by injection cycle, but the posted figures do not include a cycle-by-cycle breakdown. The record also does not give confidence intervals for the counts, detailed event definitions, or a statistical model for the primary endpoint. Therefore, the apparent precision of the raw counts should not be confused with precision about an underlying event probability or with evidence about differences between treatment options.
General: a confidence interval expresses the uncertainty around an estimate under a statistical model. No confidence intervals for the primary safety counts are reported in the registry record, so the numerical uncertainty around those counts cannot be assessed from the record. The absence of such intervals does not change the counts; it limits how fully their precision can be characterized.
9. Statistical Methods Explained
The registry identifies the primary outcome as a number of participants and describes the measure as the occurrence of treatment-emergent adverse events overall and per injection cycle. Its stated safety-evaluable set includes participants treated with the investigational product at least once. The posted risk set is 370 participants for serious adverse events and 370 for other adverse events, with affected-participant counts of 16 and 20, respectively. These are descriptive summaries. No primary-outcome analysis results beyond the reported counts are described in the registry record.
What does a participant count represent?
General: a participant count records how many people meet an outcome definition during a stated observation period. It differs from an event count, because one participant may experience more than one event. It also differs from a rate, which requires a specified time denominator, and from a time-to-event analysis, which uses information about when events occur. The registry describes the primary endpoint in terms of participants affected; detailed methods for handling repeated events are not reported in the registry record.
Why does the single-group design matter?
General: a controlled comparison can help separate an outcome observed under treatment from the background occurrence of that outcome. In a single-group study, there is no concurrent control group to provide that comparison. The counts can describe what was observed among treated participants, but they cannot by themselves estimate a difference attributable to treatment. The study is also open-label, so participants and study personnel were not masked to treatment according to the registry listing. The record does not describe procedures intended to reduce possible effects of awareness on assessment or reporting.
How should uncertainty be considered?
General: statistical uncertainty concerns how much an observed estimate might vary across comparable samples under specified assumptions. Confidence intervals are one common way of expressing uncertainty. The registry record does not report confidence intervals for the primary adverse-event counts, nor does it report a model or hypothesis test for that endpoint. No recalculated estimate should be treated as a substitute for a sponsor analysis. In particular, the listed counts alone do not supply enough detail to reconstruct a model-based analysis, account for event timing, or assess adjustment for other factors.
What can repeated injection cycles add?
The primary outcome is described both overall and per injection cycle, and the secondary outcomes also refer to selected visits within cycles. General: repeated measurements can describe whether observations change over time, but their analysis must account for how observations from the same participant are related. The registry record does not report the analysis method for repeated cycles or the cycle-specific primary results. It therefore does not support conclusions about whether adverse events became more or less frequent across cycles.
What do the planning illustrations mean?
General: sample-size calculations are planning tools that describe the sample size associated with specified assumptions. They are not observed trial results and should not be read as observed power. The planning illustrations associated with this analysis 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. The record states that these are illustrations based on the observed effect, not the trial’s own design. Since this study is single-group and non-controlled, those two-arm assumptions do not describe its design. The registry record does not report the study’s own sample-size justification.
General: over-dispersion occurs when observed variability is greater than a statistical model assumes. It can affect uncertainty estimates in settings where event counts vary more widely than expected under a simple model. The registry record does not report a count model or evidence about over-dispersion for this endpoint, so it is not possible to say whether such a model issue arose in the sponsor’s analysis. More broadly, the analysis methods, handling of repeated events, and any adjusted or sensitivity analyses are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures. The named secondary outcomes cover tolerability, changes in plantar-flexor scores and spasticity assessments, impressions of change from investigators and families, pain, and gross motor function. Multiple outcomes and multiple timepoints can create a multiplicity issue: general statistical practice recognizes that testing many questions can increase the chance of at least one apparently notable result occurring by chance. Whether and how that issue was addressed is not reported in the registry record. No multiplicity adjustment or hierarchy among outcomes is described.
Missing-data methods are also not reported in the registry record. The record does not explain how unavailable assessments, withdrawals, or incomplete follow-up were handled for the primary or secondary outcomes. It does not provide outcome-specific analysis populations beyond the safety-evaluable set, defined as participants who received the investigational product at least once. The registry lists 370 participants in the adverse-event risk set, but that does not establish how many contributed data to each secondary measure or visit.
The registry record does not report an interim-analysis plan, a detailed statistical analysis plan, or sensitivity analyses for missing observations. These absences matter because different approaches to incomplete follow-up or multiple outcome testing can affect estimates and their uncertainty. They do not change the reported participant counts, but they limit assessment of the full analytical process.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | 16 | 370 | 4.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | 0 of 370 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | 20 of 370 |
Most frequent serious adverse event terms
| Event term | Organ system | 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) |
|---|---|---|
| Gastroenteritis | Infections and infestations | 3 of 370 |
| Tenotomy | Surgical and medical procedures | 2 of 370 |
| Epilepsy | Nervous system disorders | 2 of 370 |
| Bronchitis | Infections and infestations | 2 of 370 |
| Cast application | Surgical and medical procedures | 1 of 370 |
| Arrhythmia | Cardiac disorders | 1 of 370 |
| Clonic convulsion | Nervous system disorders | 1 of 370 |
| Febrile convulsion | Nervous system disorders | 1 of 370 |
| Seizure | Nervous system disorders | 1 of 370 |
| Gastritis | Gastrointestinal disorders | 1 of 370 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) |
|---|---|---|
| Nasopharyngitis | Infections and infestations | 20 of 370 |
Serious events with the highest arm-level rate: gastroenteritis (0.8%), tenotomy (0.5%), epilepsy (0.5%), bronchitis (0.5%), cast application (0.3%).
The registry reports 16 participants affected by serious adverse events and 20 affected by other adverse events, with a risk set of 370 for each category. It reports 0 deaths. The serious-event terms listed with percentages are Gastroenteritis (0.8%), Tenotomy (0.5%), Epilepsy (0.5%), Bronchitis (0.5%), Cast application (0.3%), and Arrhythmia (0.3%). These are descriptive entries in the registry record.
General: serious adverse events and other adverse events are distinct reporting categories, and their definitions determine which events belong in each category. The registry record does not include the detailed definitions or explain whether the same participant could appear in both counts. The term list also does not establish that an event was caused by treatment. Attribution, event timing, severity details, and recurrence are not reported in the registry record.
Because the study has no control group, the counts cannot be interpreted as a comparative excess or reduction in risk. They describe events recorded in the treated group during the stated follow-up period. The figures are not a complete account of event characteristics, and the listed percentages should be read as the registry’s reported values rather than as a basis for deriving additional rates.
12. What the Result Does, and Does Not, Mean
The posted results describe adverse events among participants treated with incobotulinumtoxinA in a long-term, open-label, single-group study. The registry reports 16 participants with serious adverse events, 20 with other adverse events, and 0 deaths, with 370 participants in each stated risk set. It also lists selected serious-event terms and their reported percentages. These observations provide a descriptive account of the safety experience recorded in the study.
They do not establish whether treatment caused any particular event. Without a control group, there is no concurrent comparison that shows how often similar events might have occurred in a comparable group receiving a different treatment or no study treatment. The open-label design also leaves the study unmasked. The counts do not, by themselves, describe event timing, duration, recurrence, or each participant’s full experience.
The primary endpoint was intended to describe events overall and per injection cycle, but cycle-specific figures are not reported in the registry record. Numerical results for the listed secondary assessments are also not reported in the registry record. As a result, the available results do not support conclusions about changes in spasticity, pain, motor function, or impressions of change.
General: statistical evidence is most informative when the outcome definition, analysis method, uncertainty, and relevant comparison are all clear. Here, the record supplies an endpoint description and participant counts, but does not report confidence intervals or detailed analysis procedures. The findings should therefore be understood as a registry-level description of observed events in this study population, not as a complete comparative evaluation of safety or efficacy. Nothing in these counts alone establishes that an intervention works or does not work.
13. Why This Trial Matters Statistically
This study illustrates why design and endpoint definitions matter when reading clinical-trial safety results. A participant count can offer a direct description of how many people were recorded as affected, while still leaving important questions unanswered. The registry describes the primary measure as participants with treatment-emergent adverse events during follow-up, overall and per injection cycle. That framing is useful, but the posted figures do not provide the cycle-specific breakdown.
The single-group, open-label design is central to interpretation. Counts from a treated group can characterize that group’s recorded experience, but without a control group they cannot estimate a comparative difference. This distinction is important in long-term studies, where events may be observed over an extended period and a descriptive count is not equivalent to a causal conclusion.
The record also shows how outcome breadth can complicate interpretation. It lists 10 outcome measures, with secondary assessments spanning spasticity, impressions of change, pain, tolerability, and gross motor function. Multiplicity handling, missing-data methods, and the detailed statistical plan are not reported in the registry record. Recognizing these gaps helps readers distinguish between what is documented—the study structure, endpoint definition, and adverse-event counts—and what cannot be evaluated from the record, such as the precision of estimates or the consistency of findings across outcomes and timepoints.
Statistically, the most responsible reading keeps the observed counts separate from comparative claims. The record is informative about what was registered for this treated population, but it does not provide every analysis detail needed for a fuller assessment.
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 limitations specific to this study affect interpretation. It was open-label, non-controlled, and single-group, so there is no randomized comparator for estimating differences in adverse events or other outcomes. The registry identifies treatment-emergent adverse events as the primary endpoint, but the available results do not provide the per-cycle counts named in that endpoint. The listed adverse-event figures are therefore not a complete account of the endpoint as described.
The registry reports 16 participants affected by serious adverse events, 20 by other adverse events, and 0 deaths, but it does not provide confidence intervals, event timing, recurrence, attribution, or detailed event definitions. It also does not report whether participants could contribute to both event categories. The listed serious-event terms and percentages should not be used to infer causation or reconstruct additional statistics.
Although 10 outcome measures are listed, numerical results for the named secondary assessments are not reported in the registry record. The record does not report methods for handling missing data, multiplicity, repeated observations, or sensitivity analyses. The statistical analysis plan, interim analyses, and rationale for the planned enrollment are also not reported in the registry record. The safety-evaluable set is defined as participants treated at least once, but outcome-specific analysis populations are not described.
These limitations do not negate the descriptive counts. They constrain the conclusions that can be drawn about comparative effects, precision, changes over time, and results beyond the reported safety figures.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Long-term Open-label Study of Botulinumtoxin Type A to Treat Spasticity of Leg(s) or Leg(s) and Arm in Cerebral Palsy — NCT01905683.
- Registry record last updated 2017-10-27; status last verified 2017-09.
- Results first posted 2017-10-27.
- 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.
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18. Record Summary
The registry describes a completed Phase 3, open-label, non-controlled, single-group study of incobotulinumtoxinA in children and adolescents age 2–17 years with cerebral palsy and lower-limb or combined upper- and lower-limb spasticity. Enrollment was 370, and the listed treatment was 16–20 Units per kg body weight.
The primary endpoint counts participants with treatment-emergent adverse events from first injection through the end-of-study visit in the Week 50–66 range. The safety-evaluable set includes participants treated at least once. The record reports a risk set of 370, 16 participants affected by serious adverse events, 20 by other adverse events, and 0 deaths. It lists six serious-event terms with percentages.
The study had no control group. Cycle-specific primary results and numerical secondary-outcome results, along with detailed statistical, missing-data, and multiplicity methods, are not reported in the registry record.