MEDITOXIN® Versus BOTOX® in the Treatment of Post-stroke Spasticity of the Upper Limb Spasticity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MEDITOXIN® Versus BOTOX® in the Treatment of Post-stroke Spasticity of the Upper Limb Spasticity (NCT01313767), a randomized phase 3 study. The primary outcome is MAS(Modified Ashworth Scale) of Wrist Flexor.

2. Clinical Question

This is an active-treatment comparison rather than a comparison against no treatment or placebo. The registry identifies efficacy and safety as the broad purposes of the study. Other recorded assessments included MAS scores for elbow, finger and thumb flexors, disability, global assessment and carer burden. Those additional measures give context to the study’s scope, but they do not replace the stated primary endpoint.

The clinical question is therefore specific: how did wrist flexor tone change by week 4 in each randomized treatment arm, and how precisely was any between-arm difference estimated? The registry describes the planned measure and analysis population, but the posted record does not report the endpoint estimates needed to answer that comparison. The existence of a completed trial does not, by itself, establish the direction or size of an effect.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group, phase III trial with an active drug comparator. Its official description identifies it as a multicentre study. Medy-Tox was the sponsor. The record lists the study as completed, with a start date of 2011-03 and primary completion in 2012-01.

The study description states that approximately 196 participants would be enrolled, with a 1:1 group ratio. Enrollment is listed as 196. Each arm is described as receiving a single intramuscular treatment of its assigned product, up to 360U. Participants were to be observed every 4 weeks through 12 weeks after injection. The registry does not report further details about dose selection, treatment preparation, or how masking was maintained.

Random allocation can reduce systematic differences between groups at the point of assignment, while masking can limit some forms of bias in assessment and reporting. These are general design principles; the registry record does not describe the allocation sequence, concealment procedures, or the identities of the groups included in quadruple masking. The active-comparator structure means the planned contrast was between two botulinum toxin type A products, not between treatment and an untreated group.

The primary analysis population is described as the Full Analysis Set, with 94 participants in the Meditoxin arm and 98 in the Botox arm. The registry does not give a fuller definition of that population or explain the relationship between those analysis counts and the overall enrollment. The study description also lists safety observations, vital signs and clinical laboratory tests, including haematology, serum chemistry and urinanalysis. Detailed procedures for these assessments are 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: Total 9 subjects were prematurely discontinued from the study due to unmet inclusion/exclusion criteria found after randomization, AEs/SAEs, consent withdrawal and follow-up lost: 7 subjects in study group (7.14%) and 2 subjects in control group (2.04%). Thus total 187 subjects (91 in study group; 96 in control group) completed the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Full Analysis Set population which consisted of 94 subjects receiving Meditoxin and 98 subjects for Botox.

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: FAS

6. Primary Endpoint

The registry lists the primary outcome as MAS(Modified Ashworth Scale) of Wrist Flexor, measured over Baseline and 4 weeks.

The primary endpoint was change from baseline at week 4 in wrist flexor muscle tone, assessed using the Modified Ashworth Scale. The registry describes the scale as a commonly used clinical measure of spasticity and resistance to passive movement. Its categories range from 0, meaning no increase in tone, to 4, meaning the limb is rigid in flexion or extension.

In general, a scale focused on resistance during passive movement can provide a structured way to assess muscle tone. Using the same measure at baseline and follow-up allows the outcome to be expressed as change over the specified period. The registry’s stated focus on the wrist flexors makes the primary question narrower than an overall assessment of all upper-limb function or disability.

The registry specifies a mean and standard deviation for the primary measure. A mean describes the average score in a group, while a standard deviation describes how spread out individual scores are around that average. Because the MAS is recorded in ordered categories, a group average does not show how participants were distributed across the separate categories. The registry does not report the baseline and week 4 values, the change estimates, or their uncertainty for either group. It therefore does not allow the size or precision of the primary endpoint comparison to be assessed from the record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized parallel-group comparison, a continuous-outcome summary using a mean and standard deviation, and a primary endpoint based on change from baseline. The results needed to evaluate the primary comparison are not reported in the registry record. The explanations below describe general statistical ideas relevant to this design; they do not establish which specific procedures the investigators used.

What does randomization contribute?

In general, randomization assigns participants to groups using a chance-based process. Its purpose is to make systematic baseline differences less likely, so that comparisons between groups can be interpreted more fairly. Randomization does not guarantee that groups will be identical in every characteristic, especially in a particular trial. The registry says the study was randomized, but the sequence-generation and allocation-concealment methods are not reported in the registry record.

Masking is another general safeguard. When people involved in treatment, assessment or trial conduct do not know the assigned group, expectations may be less likely to influence care or outcome measurement. The record labels masking as quadruple, but does not specify which roles were masked or describe the procedures used to preserve masking. The label alone does not show whether masking was maintained throughout the study.

How should change from baseline be understood?

Change from baseline compares a participant’s follow-up score with that participant’s starting score. A group summary of these changes can describe average movement on the scale during the specified period. A between-group contrast in average change would address whether the groups differed in their average change, rather than whether either group changed in isolation. The registry defines the primary endpoint as change at week 4, but reports neither the group changes nor the contrast.

Baseline adjustment is a general analytical approach that can account for starting measurements when comparing follow-up outcomes. It can improve precision in some settings, but the exact analysis model matters. The registry does not report whether the primary analysis used a model adjusted for baseline, an analysis of change scores, or another approach. It also does not report the assumptions or diagnostics for any model.

What do the mean and standard deviation describe?

A mean summarizes the average of a set of scores. A standard deviation describes how much individual scores vary around that average. Together they are useful summaries, but they do not show the full score distribution or identify how many participants occupied each MAS category. General statistical interpretation should consider whether a mean adequately represents the underlying ordered scale and whether the chosen analysis accounts for its properties. The registry specifies the mean and standard deviation, but does not report the observed values.

A confidence interval is a general way to express uncertainty around an estimated effect. It gives a range of values compatible with the data under the statistical model and its assumptions. A narrow interval indicates greater precision than a wide interval, though precision is not the same as clinical importance. The registry record does not report a confidence interval for the primary comparison, so neither precision nor the range of effects compatible with the results can be assessed.

Why does multiplicity matter?

When many outcomes, time points or statistical tests are examined, the chance of finding at least one apparently notable result can rise. This is the general multiplicity problem. Researchers may address it through a prespecified hierarchy, adjustment procedures, or by treating secondary analyses as exploratory. The record lists 19 outcome measures and 50 analyses, but does not report a multiplicity strategy, a testing hierarchy, or which analyses were confirmatory. It is therefore not possible to determine from the registry record how the reported analysis set was controlled or interpreted.

What do the planning illustrations mean?

Sample-size calculations are planning tools, not evidence of what happened in a trial. The planning illustrations associated with this comparison are described as using the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is set as a stated fraction of the observed effect. For non-time-to-event outcomes, such calculations are expressed as participants per arm for 80% power or another stated power level. They are illustrations based on assumptions, not observed power and not the trial’s documented original design justification. The specific illustration values and the trial’s own sample-size justification are not reported in the registry record.

In general, power is the probability that a planned test will detect an effect of a specified size under specified assumptions. It is not a property that can be read from a completed trial’s observed results as a measure of whether the study succeeded. The registry does not report the original sample-size calculation, the target effect, or the assumptions used for the trial’s design. Those details should not be inferred from a planning illustration based on an observed effect.

How should adverse-event counts be read?

Counts of participants with events are descriptive safety summaries. They do not, on their own, show when an event occurred, how long it lasted, whether one participant had more than one event, or whether investigators considered it related to treatment. In general, comparisons of event counts should be interpreted alongside definitions, exposure time, event severity and the method of collection. Those details are not fully reported in the registry record. The available counts should therefore be read as recorded participant counts, not as proof of causation or as a complete safety profile.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 19 outcome measures and 50 analyses. The named outcomes include MAS assessments for wrist, elbow, finger and thumb flexors, along with improvement rates for these measures. A larger family of outcomes and analyses raises a general multiplicity concern: the more comparisons examined, the more important it is to know which questions were primary and whether any adjustment or hierarchy was planned. The registry does not report a multiplicity strategy or identify the status of each analysis.

The stated primary endpoint focuses on wrist flexor MAS change from baseline at week 4. The registry’s analysis description indicates that the primary outcome has several categories or time points and is not reduced to one comparison. As a result, a single primary comparison cannot be reconstructed from the record. The analysis plan, including how the endpoint’s categories or time points were handled, is not reported in the registry record.

The Full Analysis Set is described as 94 participants receiving Meditoxin and 98 receiving Botox. The record does not provide a fuller definition, participant flow by analysis, or an explanation of why these are the analysis counts. It also does not report the amount or pattern of missing outcome data, the method used to handle missing measurements, or any sensitivity analysis. These gaps limit assessment of whether missingness could have influenced the endpoint results.

Although the registry identifies a primary measure and analysis population, the statistical model, test, assumptions, and handling of multiplicity are not reported. The primary endpoint estimates themselves are also absent. Accordingly, the record does not permit a complete appraisal of the primary analysis or of how additional analyses should be weighed against it.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cholecystitis acute (2.0%), convulsion (2.0%), hepatitis toxic (1.0%), intraventricular haemorrhage (1.0%), inguinal hernia (1.0%).

The registry reports serious adverse events affecting 5 participants in the Meditoxin arm and 8 in the Botox arm, with 98 participants at risk in each arm. Other adverse events affected 35 participants in each arm, again with 98 at risk in each arm. These are counts of participants, not a description of the number of distinct events or their timing. The record does not report deaths.

The serious-event terms listed include Cholecystitis acute (2.0%), Convulsion (2.0%), Hepatitis toxic (1.0%), Intraventricular haemorrhage (1.0%), Inguinal hernia (1.0%) and Pyelonephritis acute (1.0%). The registry record does not attribute these listed terms to a particular treatment arm. They should therefore not be interpreted as arm-specific rates or direct comparisons.

In general, adverse-event counts describe what was recorded, not necessarily what was caused by treatment. The record does not report event-level timing, duration, severity, relatedness assessments, or exposure-adjusted summaries. The counts are useful for describing the posted safety information, but they do not by themselves establish a difference in safety between the treatments or provide a complete account of risks.

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

The registry record establishes that this was a randomized, masked, active-comparator trial of Meditoxin and Botox for post-stroke upper-limb spasticity. It specifies a primary efficacy measure: change from baseline at week 4 in wrist flexor tone on the MAS. It also gives the primary analysis population counts and selected adverse-event counts. These are details about the trial’s design and posted data, not evidence of a particular efficacy result.

The key limitation for interpreting efficacy is that the record does not report the primary endpoint estimates or the between-group comparison. Without those values, it is not possible to state whether the groups had similar or different average changes, in which direction any difference went, or how precisely it was estimated. The completion status of a trial does not fill this information gap.

The safety counts show that serious adverse events affected 5 participants in the Meditoxin arm and 8 in the Botox arm, while other adverse events affected 35 participants in each arm. Those observations are descriptive. They do not establish that a product caused an event or that one product is safer. Further context, including event attribution, timing and severity, is not reported in the registry record.

In general, a statistically detectable difference and a clinically meaningful difference are distinct questions. A statistical estimate describes the size and uncertainty of a contrast under an analysis; clinical importance requires interpretation in context. Here, the primary estimate and its uncertainty are not reported, so neither question can be answered from the registry record. The record also does not describe a multiplicity approach, missing-data handling or the detailed statistical model.

The appropriate conclusion is limited: the registry describes a direct comparison and selected safety information, but does not report the primary efficacy results needed to characterize the treatment contrast. No conclusion about comparative efficacy or overall safety follows from the information reported alone.

13. Why This Trial Matters Statistically

This trial is statistically notable for the structure of its question. It compares two active treatments in a randomized, masked, parallel-group design and defines a specific primary outcome at a specific follow-up point. Such a design can support a direct between-group comparison when the allocation, outcome measurement and analysis are carried out as planned. The registry provides the design labels and endpoint definition, but not enough information to evaluate those implementation details.

The endpoint also illustrates why the scale and summary measure matter. MAS scores are ordered categories, while the registry specifies a mean and standard deviation. In general, averages offer a compact summary, but may conceal the distribution across categories. Understanding the full result would require the reported estimates and, where available, supporting detail about the score distribution and analysis assumptions.

The record lists 19 outcome measures and 50 analyses, which highlights the importance of a clear prespecified primary question and transparent handling of multiple comparisons. Without that information, readers cannot tell how confirmatory findings were distinguished from additional analyses. Missing-data methods and analysis-population definitions are similarly important to judging whether the estimate represents the randomized groups fairly.

The registry’s safety counts are also a reminder that event totals need context. Counts can describe recorded events, but causal interpretation depends on timing, relatedness, severity and other study details. Because the primary efficacy estimates and much of the analysis plan are not reported, the record supports examination of the trial’s design and reporting completeness more strongly than interpretation of a treatment effect.

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 is that the registry does not report numerical results for the primary endpoint. It describes the week 4 wrist flexor MAS change and the Full Analysis Set, but no group means, changes, between-group estimate, confidence interval or statistical test is reported. The primary efficacy comparison therefore cannot be quantified or assessed for precision.

The analysis population is reported as 94 participants in the Meditoxin arm and 98 in the Botox arm, while total enrollment is listed as 196. The registry does not explain participant flow, provide a fuller definition of the Full Analysis Set, or state how many participants contributed primary endpoint data. Missing-data amounts and handling are not reported.

The record gives a mean and standard deviation for the primary measure, but does not provide the observed values or explain the statistical model. The MAS is an ordered scale; the registry does not report how its categorical structure was treated analytically or provide category-level distributions. It also does not report the multiplicity strategy despite listing 19 outcome measures and 50 analyses.

Safety reporting is limited to participant counts and a list of serious-event terms with percentages. The listed terms are not assigned to arms in the record. Event timing, duration, severity, relatedness, and detailed definitions are not reported, and deaths are not reported in the registry record.

Finally, the registry does not report the trial’s original sample-size justification, allocation procedures, masking procedures, or detailed analysis plan. These limitations restrict interpretation of both the primary efficacy question and the broader safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: MEDITOXIN® Versus BOTOX® in the Treatment of Post-stroke Spasticity of the Upper Limb Spasticity — NCT01313767.
• Registry record last updated 2019-03-29; status last verified 2019-03.
• Results first posted 2019-03-29.
• 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

NCT01313767 is a completed phase III randomized, quadruple-masked, parallel-group, active-drug-controlled trial sponsored by Medy-Tox. It compared MEDITOXIN® with BOTOX® for post-stroke upper-limb spasticity. The record lists enrollment of 196 and identifies the primary endpoint as change from baseline at week 4 in wrist flexor tone, measured with the Modified Ashworth Scale.

The Full Analysis Set is described as 94 participants receiving Meditoxin and 98 receiving Botox. Primary outcome estimates and the between-group comparison are not reported in the registry record. Serious adverse events affected 5 participants in the Meditoxin arm and 8 in the Botox arm; other adverse events affected 35 participants in each arm. Further detail on the analysis plan, missing data and event attribution is not reported in the registry record.