Study Of GSK1358820 In Patients With Post-Stroke Upper Limb Spasticity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Of GSK1358820 In Patients With Post-Stroke Upper Limb Spasticity (NCT00460564), a randomized phase 3 study. The primary outcome is Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Wrist Score to the End of the DB Phase (Week 12) in the High-dose Groups.

2. Clinical Question

3. Trial Design

NCT00460564 was a Phase 3, randomized, quadruple-masked, parallel-group study sponsored by GlaxoSmithKline. The registry record gives an enrollment of 109 and describes a double-blind, placebo-controlled treatment phase followed by an open-label treatment phase. The study status is completed. The recorded start was 2007-05, and primary completion was 2008-12.

The primary comparison concerns the high-dose groups during the double-blind phase: High-Dose BTX and High-Dose Placebo. The registry also lists Low-Dose BTX and Low-Dose Placebo, and reports a low-dose secondary AUC outcome. The primary analysis group counts were 51 for High-Dose BTX and 26 for High-Dose Placebo. These are analysis-group counts for the posted primary outcome; the registry record does not provide arm descriptions beyond the group labels.

Quadruple masking and random allocation are design features intended to limit bias, but the registry record does not specify the roles masked or the allocation procedure. It also does not report the original sample-size justification, the protocol’s full statistical analysis plan, or whether interim analyses were planned or performed. The primary endpoint was measured from baseline through Week 12 in the double-blind phase, rather than across the later open-label period. The registry record’s description of the primary analysis population excludes randomized participants who received no investigational product and those with no post-treatment MAS wrist assessment.

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.

Only the first 6 of 8 groups are shown.

Double-Blind Phase (12 Weeks)

Reasons for not completing this period:

Open-Label Phase (36 Weeks)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS wrist score

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 Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Wrist Score to the End of the DB Phase (Week 12) in the High-dose Groups, measured over Baseline, Week 12.

The primary endpoint was the area under the curve (AUC) for change from baseline in Modified Ashworth Scale wrist score through the end of the double-blind phase at Week 12. MAS wrist score is recorded on a 6-point scale: 0, 1, 1+ (regarded as 1.5), 2, 3, and 4. The scale description defines 0 as no increase in muscle tone and 4 as the affected part being rigid in flexion or extension.

For each assessment time in the double-blind phase, the change from baseline was plotted against time, and the area between that change curve and the horizontal axis was calculated. The AUC, expressed in Score*week, serves as a summary index that incorporates the changes over the assessed period rather than using only a single assessment. Negative changes indicate improvement, and the AUC consequently has a negative sign when the accumulated changes are negative.

This endpoint was used to assess the wrist component of post-stroke upper limb spasticity over time. It does not directly summarize every aspect of spasticity or function. The registry record also lists secondary outcomes involving MAS finger score and Disability Assessment Scale domains, including hygiene, pain, dressing, limb posture, and the principal measure. Those measures address other aspects of the condition but are not part of the primary AUC definition.

7. Results Posted in the Registry

• High-Dose BTX: mean -10.40 versus -3.57 on control; difference -6.83 (95% CI -9.88 to -3.78), standardized effect d = -0.88; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Wrist Score to the End of the DB Phase (Week 12) in the Low-dose Groups

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Low-Dose BTX: mean -10.04 versus -6.23 on control; difference -3.81 (95% CI -9.91 to 2.29), standardized effect d = -0.47; z-test p = 0.221.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low-Dose BTX and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering MAS wrist and finger scores and Disability Assessment Scale measures, including principal measure, hygiene, pain, dressing, and limb posture. It also lists the low-dose AUC for MAS wrist score through Week 12. These outcomes extend the assessment beyond the primary high-dose wrist AUC, but the registry record does not provide numerical results for most of the listed secondary outcomes in the available results.

For the low-dose AUC comparison, the posted means are -10.04 for Low-Dose BTX and -6.227 for Low-Dose Placebo. The simple recalculation gives a mean difference of -3.809, a confidence interval from -9.911 to 2.293, and an unadjusted p-value of 0.221. The interval includes zero. This result is less precise than the high-dose primary comparison and does not provide clear evidence of a low-dose difference under the unadjusted calculation.

The secondary outcomes relate to the primary result by measuring other aspects of MAS wrist change, finger tone, and disability-related domains. They can offer broader context, but they do not independently confirm the primary finding merely because they appear in the same study. No overall pattern across the unreported secondary outcome results can be established from the registry record.

Unadjusted secondary results carry less weight because a study may examine multiple outcomes, creating more opportunities for apparently notable findings by chance. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting these secondary measures. The low-dose p-value should therefore be treated as an unadjusted result, and the absence of posted numerical values for the other outcomes prevents a fuller assessment of consistency across endpoints.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Wrist Score to the End of the DB Phase (Week 12) in the Low-dose Groups
• Mean Change From Baseline in MAS Wrist Score From Baseline to Week 12 of the Double-blind Phase
• Mean Change From Baseline in MAS Finger Score From Baseline to Week 12 of the Double-blind Phase
• Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Principal Measure From Baseline to Week 12 of the Double-blind Phase
• Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Hygiene From Baseline to week12 of the Double-blind Phase
• Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Pain From Baseline to Week 12 of the Double-blind Phase
• Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Dressing From Baseline to Week 12 of the Double-blind Phase
• Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Limb Posture From Baseline to Week 12 of the Double-blind Phase

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score-based summary, and the reported group summaries are means with standard deviations. A mean describes the center of the observed values, while the standard deviation describes how much individual values varied around that mean. For High-Dose BTX, the mean AUC was -10.4 and the standard deviation was 8.931; for High-Dose Placebo, the mean was -3.567 and the standard deviation was 4.719. These measures describe the observed analysis groups, not the precision of the difference between their means.

The registry reports a two-sided t-test and a mean difference (net). A t-test assesses whether the observed difference in group means is compatible with a null hypothesis of no mean difference, under the assumptions of the method. “Two-sided” means that evidence in either direction is considered. The reported mean difference is -6.830, with p < 0.001. A small p-value indicates that a difference at least as incompatible with the null would be unusual under that null and the test assumptions; it is not the probability that the null is true and does not state the probability that the result will replicate.

The sign matters because of the outcome definition. Negative MAS changes indicate improvement, and the AUC retains a negative sign when the change curve has negative accumulated area. Accordingly, the negative difference reflects a more negative average AUC in the High-Dose BTX group relative to High-Dose Placebo under the reported contrast. It is not a percentage change or a standardized scale. The unit is Score*week.

A confidence interval gives a range of values compatible with the observed data and the method used to construct the interval. It communicates uncertainty in the estimated mean difference. The registry-reported 95% interval is -10.567 to -3.093. A recalculation from the posted means, standard deviations, and group sizes gives -9.879 to -3.781. Both intervals lie below zero, although their widths and endpoints are not identical. The recalculation is an unadjusted calculation from summary statistics, so it cannot recreate every possible detail of the original analysis.

In general, the standard error of an estimated mean difference reflects both within-group variability and the amount of information in each group. More variable observations and smaller groups tend to make the estimate less precise. The reported group standard deviations and sizes therefore matter when interpreting how much uncertainty surrounds the point estimate. The displayed standard deviations should not be confused with the confidence interval: one describes variation among observed participants, while the other describes uncertainty about the group difference.

The primary analysis population is described as the Full Analysis Set. It includes randomized participants except those who received no investigational product and those without a post-treatment MAS wrist assessment. This definition clarifies who contributed to the primary endpoint analysis, but the registry record does not explain how any other missing follow-up observations were handled. It does not report whether imputation, a repeated-measures model, or another approach was used for incomplete measurements. Those details can affect an estimate when data are missing, so they cannot be reconstructed from the group summaries alone.

Randomization is intended to make treatment groups comparable on average with respect to factors known and unknown at assignment. Masking is intended to reduce the influence of expectations on care, assessment, and reporting. The registry labels the study randomized and quadruple-masked, but does not describe the specific implementation of either feature. The design is parallel-group, meaning the comparison is between assigned groups rather than a within-person crossover. The primary comparison is placebo controlled and was assessed in the double-blind phase.

The primary endpoint’s AUC is a time-integrated summary. In general, this can retain information about the trajectory of measurements across the period rather than relying only on the final visit. Its interpretation depends on the observed assessment schedule and the method used to calculate the curve; the registry record describes the broad calculation but does not provide the full computational details or participant-level values. It reports baseline and Week 12 as the timeframe and describes change at each time point in the double-blind phase.

The low-dose secondary analysis uses the same type of continuous AUC outcome. Its posted group means and standard deviations allow a simple recalculation of an unadjusted difference and interval. This is distinct from a sponsor-reported inferential analysis: no sponsor-reported analysis is listed for that secondary outcome in the registry record. The low-dose recalculation should therefore be read as a descriptive statistical supplement, not as a substitute for a prespecified trial analysis.

11. Confidence Intervals and Precision

Precision is conveyed most directly by the confidence interval around the mean difference. The registry-reported estimate for the high-dose comparison is -6.830, with a 95% confidence interval from -10.567 to -3.093. The interval is entirely below zero, indicating that the sponsor’s reported analysis places the mean difference on the negative side under its method. Its range also shows that the point estimate is not known without uncertainty.

The unadjusted recalculation from the posted summary statistics gives -6.83, with an interval from -9.879 to -3.781. The interval differs from the registry-reported interval, although both have negative endpoints and both are paired with p < 0.001. The recalculation uses the posted means, standard deviations, and group sizes; it is not an independent participant-level replication of the sponsor’s analysis. The registry record does not explain the reason for the difference in interval limits.

In general, a 95% confidence interval is produced by a procedure that, under its assumptions, would cover the true parameter in 95% of repeated applications. It is not a range that assigns a 95% probability to the true value for this particular study. The location and width of an interval are both informative: location conveys the direction and scale of compatible differences, while width conveys precision. The interval should be read in the score-week units of the AUC and alongside the endpoint’s negative-change convention.

The low-dose recalculated interval, -9.911 to 2.293, includes zero and is wider relative to its estimate than the high-dose intervals. This reflects greater uncertainty in that secondary comparison, whose group sizes were 21 and 11. The registry does not post a sponsor-reported interval for the low-dose comparison. Neither interval width nor statistical significance alone determines clinical relevance; the registry record does not report a threshold for a meaningful difference.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculation. For these continuous outcomes, the entries are participants per arm, not total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers an effect to detect equal to the stated fraction of the observed effect.

The columns for 80% and 90% power describe the number of participants per arm that a hypothetical future comparison would require, under those assumptions, to have the stated probability of detecting the specified effect if that effect were the true one. The 90% power column calls for more participants per arm than the 80% column for a given effect fraction. Rows that plan for 75% or 50% of the observed effect assume a smaller difference than the full observed effect; smaller effects need more participants to detect under otherwise unchanged assumptions.

For the high-dose comparison, the illustration lists 21 participants per arm for 80% power and 28 for 90% power when planning for 100% of the observed effect. Planning for 75% lists 37 and 49, and planning for 50% lists 82 and 110. These figures are not a report of the trial’s actual allocation target or its enrollment rationale. The registry record does not report the original sample-size assumptions or justification.

These figures are not observed power. They are prospective calculations using the observed effect as a planning input, and they do not measure the probability that the completed trial’s result is true. The planning illustration also assumes equal allocation, whereas the posted analysis-group sizes are not equal. The assumptions are simplified and do not incorporate any unreported features of the trial’s design or analysis.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -6.830; pooled standard deviation σ = 7.785.
2. n = 2 × (1.96 + 0.842)² × 7.785² / -6.830² = 20.4, rounded up to 21 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -6.83                      # observed difference in means
sigma <- 7.78469131458232                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(460564)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 21 (80% power), 28 (90% power)
 75% of observed effect: n per arm = 37 (80% power), 49 (90% power)
 50% of observed effect: n per arm = 82 (80% power), 110 (90% power)
power.t.test: 21.4 
Simulated power at n = 21 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s sponsor-reported analysis is a two-sided t-test of the high-dose groups. It reports a mean difference (net) of -6.830, a 95% confidence interval from -10.567 to -3.093, and p < 0.001. The simple recalculation from the posted summary statistics gives a mean difference of -6.83, a confidence interval from -9.879 to -3.781, and p < 0.001.

The reported and recalculated point estimates agree to the displayed precision, and their p-values are both below 0.001. The interval limits differ. The recalculated result is based only on the posted group means, standard deviations, and sizes, so it should be treated as a check using summary data rather than an attempt to reproduce the sponsor’s full analysis. The registry record does not explain the interval difference, and no reason should be inferred from the available statistics.

The sponsor analysis is the trial’s reported inferential result. The recalculation is useful for understanding what the posted summaries imply under a simple unadjusted approach, but it does not provide additional evidence from new participants or a more complete analysis. It also does not establish whether the original analysis used further specifications beyond the reported t-test.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome and lists secondary outcomes, but it does not report a multiplicity-control strategy. When several hypotheses are tested, the chance of at least one apparently notable result can increase. Statistical procedures for multiplicity can address that issue, but the registry record does not say whether adjustments, gatekeeping, or a prespecified hierarchy were used. The reported p-values should therefore be interpreted in light of the analysis they describe; the low-dose comparison is explicitly an unadjusted recalculation.

The primary analysis population is described as the Full Analysis Set: randomized participants except those who received no investigational product or had no assessment of post-treatment MAS wrist score. This is the population definition in the registry record, not a complete account of all data-handling decisions. The record does not report how missing assessments after treatment initiation were handled, whether participants with partial follow-up contributed to the AUC, or whether any imputation or sensitivity analyses were performed.

Missing data can affect both the estimated group difference and its uncertainty, particularly if the probability of missingness relates to participants’ outcomes. Without a reported missing-data method and participant-level follow-up information, the effect of missing observations cannot be assessed. The exclusion of participants with no post-treatment MAS wrist assessment is stated, but further assumptions about their outcomes would be speculative.

The registry record also does not report interim analyses, stopping rules, or a complete statistical analysis plan. Those details matter for assessing how the analyses were selected and whether the reported inference reflects prespecified decisions. Their absence from the record does not establish that such procedures were or were not used. The trial’s original sample-size justification is also not reported, so the planning illustrations based on observed effects should not be mistaken for the rationale behind the study’s enrollment.

16. 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: syncope (5.0%), emphysema (5.0%), herpes zoster (5.0%), muscular weakness (5.0%), bronchitis chronic (4.8%).

The registry reports serious adverse events by listed study group. In the double-blind high-dose groups, serious adverse events affected 6 of 51 participants in High-Dose BTX and 3 of 26 in High-Dose Placebo. The corresponding low-dose groups report 1 of 21 and 0 of 11. The later group labels include double-blind and open-label treatment sequences; their serious adverse event counts are reported separately and should not be combined with the initial group figures.

These are counts of participants affected, not counts of every event, and the group sizes are the reported at-risk counts for those listings. The registry also lists serious-event terms and percentages, including Syncope, Emphysema, Herpes zoster, and Muscular weakness at 5.0% each. The record does not attach those top-term percentages to a specific comparison in the information available, so they should not be read as direct group-specific rates.

Deaths are not reported as numeric values in the adverse-event information. That does not establish that there were no deaths. The listed serious-event counts alone do not determine comparative safety, and the registry information does not provide the detail needed to assess event timing, severity, causality, or statistical uncertainty.

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

The primary result describes a difference in mean AUC for change from baseline in MAS wrist score between the high-dose GSK1358820-labelled group and placebo during the double-blind phase through Week 12. The registry-reported estimate is negative, and its 95% confidence interval remains below zero. Under the endpoint’s sign convention, this is evidence of a more negative accumulated change in the high-dose group than in placebo in the primary analysis population.

The result does not, by itself, establish the clinical importance of that difference. The registry record does not report a threshold for a meaningful change in AUC, and the endpoint is a summary of MAS wrist score over time rather than a direct measure of every functional or patient-reported consequence. Other listed outcomes concern finger score and disability domains, but most of their numerical results are not reported in the registry record.

The primary finding also does not resolve the low-dose comparison. Its unadjusted recalculation has a confidence interval that includes zero, and the registry record does not report a sponsor analysis for that secondary comparison. The high-dose and low-dose analyses should not be combined into a dose-response claim, especially without a reported formal comparison across doses.

The trial’s primary endpoint covers the double-blind period, not the later open-label phase. It therefore does not describe longer-term results from open-label treatment. The posted group summaries do not show individual trajectories, the distribution of changes, or how unreported missing-data and multiplicity decisions may have affected inference. The result is a statistical comparison for a specified measure and period, not a complete account of treatment effects, safety, or individual outcomes.

Finally, a p-value below 0.001 is evidence against a no-difference hypothesis under the reported test assumptions; it is not a measure of treatment benefit, clinical relevance, or certainty that the finding will recur. The confidence interval provides the more direct description of the range and precision of the estimated difference, while the endpoint definition supplies its clinical measurement context.

18. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition is essential to interpreting a treatment comparison. AUC for MAS wrist score summarizes changes across the double-blind assessment period, and its negative sign has a specific meaning because negative changes from baseline indicate improvement. Reading the numerical direction without that sign convention could lead to a mistaken interpretation.

It also illustrates the distinction between the primary analysis and secondary exploration. The high-dose AUC is the primary comparison, while the registry includes low-dose AUC and several other MAS and disability-related outcomes. Those additional outcomes can broaden the clinical picture, but they do not carry the same confirmatory role when a multiplicity plan and complete outcome results are not reported.

The registry provides both a sponsor-reported analysis and enough summary statistics for a simple recalculation. Their point estimates and p-values are close, while their confidence intervals differ. This is a useful reminder that matching an estimate from summary data does not necessarily reproduce the original inferential method in every detail. Reporting the analysis population, interval, test, and endpoint units helps readers understand what has been estimated and what remains uncertain.

The sample-size illustrations show how planning requirements change when the target effect is reduced, but they are based on the observed effect rather than the original design assumptions. Keeping planning illustrations separate from the study’s own rationale prevents retrospective calculations from being mistaken for prospective design evidence or observed power.

19. 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 registry record does not provide the original sample-size justification, a complete statistical analysis plan, or details of interim analyses. It also does not explain the method used to handle missing observations beyond defining who was excluded from the Full Analysis Set. These omissions limit assessment of the prespecification and robustness of the primary estimate.

The primary outcome is a score-based AUC through Week 12. The record describes the scale and broad area calculation, but does not provide individual-level values, the full assessment schedule, or enough detail to independently reproduce the AUC. The posted means and standard deviations cannot show the distribution of participant responses or whether a smaller subset had unusually large changes.

The reported primary confidence interval and the interval from the simple summary-statistic recalculation have different limits. The registry does not explain that difference. The recalculation cannot resolve it because it does not use participant-level data or any unreported analysis specifications. The low-dose result is also only an unadjusted recalculation in the information available, rather than a listed sponsor-reported analysis.

Most listed secondary outcomes do not have numerical results in the registry record. Without those results and a reported multiplicity strategy, it is difficult to assess consistency across the outcome domains or distinguish confirmatory findings from exploratory ones. The top serious adverse event terms are not linked to a specific group in the record information, and death values are not reported. These limitations constrain conclusions about comparative safety and about the broader clinical profile beyond the primary statistical result.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study Of GSK1358820 In Patients With Post-Stroke Upper Limb Spasticity — NCT00460564.
• Registry record last updated 2017-05-30; status last verified 2017-05.
• Results first posted 2010-02-10.
• 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.

23. Record Summary

NCT00460564 is a completed, randomized, quadruple-masked, parallel-group Phase 3 study sponsored by GlaxoSmithKline. It evaluated GSK1358820 against placebo in patients with post-stroke upper limb spasticity, with a double-blind phase followed by open-label treatment.

The primary outcome was AUC for change from baseline in MAS wrist score through Week 12. The sponsor-reported high-dose comparison found a mean difference (net) of -6.830, with a 95% confidence interval from -10.567 to -3.093 and p < 0.001. The registry record does not report the original sample-size rationale, full missing-data procedures, or multiplicity plan.