PRidopidine's Outcome On Function in Huntington Disease, PROOF- HD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PRidopidine's Outcome On Function in Huntington Disease, PROOF- HD (NCT04556656), a randomized phase 3 study. The primary outcome is Change From Baseline in the Unified Huntington Disease Rating Scale-Total Functional Capacity (UHDRS-TFC) Score (mITT).

2. Clinical Question

3. Trial Design

The registry record identifies PROOF-HD as a Phase 3, randomized, double-blind, placebo-controlled, parallel-arm, multicenter study in people with early-stage Huntington disease. The sponsor is Prilenia. The record reports an enrollment of 499 and a completed study status. The study start date is 2020-10-16, and the primary completion date is 2023-03-14.

Participants were assigned to pridopidine or matching placebo. The active regimen was 45 mg twice daily. The registry describes masking as quadruple; it does not specify the masked roles in the posted information. A parallel-arm design compares the assigned groups over the study period rather than having each participant receive both treatments in sequence. Randomization is intended, in general, to make the groups comparable on average at assignment, while masking can reduce the influence of treatment knowledge on care, reporting, and assessment. Those are general design principles, not additional details about how this particular trial was conducted.

The main outcome was assessed from baseline to Week 65. The posted primary analysis concerns change in the Total Functional Capacity score in the modified intent-to-treat population. The registry also lists a change in the Composite UHDRS total score as a secondary outcome. It reports 11 outcome measures and 40 analyses, while the posted secondary results include one endpoint. The record does not report the original sample-size justification, the planned interim analyses, or further details of the trial's statistical plan in the information available for this summary.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The modified intent to treat (mITT) population included all participants in the ITT population who received at least one dose of study drug and had valid in clinic TFC scores both at baseline and at least one post-baseline timepoint. The mITT population was analyzed according to the treatment to which the participant was randomized. The mITT population was the main analysis population for the primary endpoint in non-EMA regions. Note that the analysis was based on observed data.

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 Change From Baseline in the Unified Huntington Disease Rating Scale-Total Functional Capacity (UHDRS-TFC) Score (mITT), measured over From baseline to Week 65.

The primary endpoint is change from baseline to Week 65 in the Unified Huntington Disease Rating Scale-Total Functional Capacity score. The registry describes the score as the sum of ratings for domestic chores, activities of daily living, finances, care level, and occupation. It ranges from 0 to 13, with 13 representing the least affected state and 0 representing complete incapacity.

Functional capacity is used to characterize how Huntington disease affects a person's ability to manage daily activities and responsibilities. In general, a repeated measure of this kind can track change over a specified period and compare the average change between randomized groups. The endpoint is reported as a least-squares mean with a standard error, and the sponsor's comparison uses a mixed models analysis. The posted estimand is a group-level contrast in score change, not a count of participants who improved or worsened.

Change is measured relative to each participant's baseline score. A negative group mean therefore indicates a lower follow-up score relative to baseline on this scale. The endpoint's direction should be interpreted alongside the scoring rule: lower scores represent greater functional limitation. A group mean does not describe every participant's course, and a between-group estimate does not by itself establish the importance of a difference to an individual.

7. Results Posted in the Registry

• Pridopidine: mean -1.18 versus -0.95 on control; difference -0.23 (95% CI -0.56 to 0.10), standardized effect d = -0.12; z-test p = 0.172.

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.

Change From Baseline to Week 65 in Composite UHDRS (cUHDRS) Total Score (mITT)

• 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 errors.
• Result:
  • Pridopidine: mean -0.99 versus -0.88 on control; difference -0.11 (95% CI -0.41 to 0.19), standardized effect d = -0.06; z-test p = 0.473.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pridopidine and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists change in Composite UHDRS total score from baseline to Week 65 as a secondary outcome, and posts results for that endpoint. Its sponsor analysis reports a mean difference of -0.11, with a 95% confidence interval from -0.4 to 0.18 and p = 0.454. The interval includes zero. The secondary estimate therefore does not establish a clear group difference in the posted analysis.

Across the primary and posted secondary outcomes, the estimates point toward more negative average change in the pridopidine group, but both reported confidence intervals include zero. This is a description of the observed pattern, not evidence that the endpoints independently confirm a treatment effect. The secondary result should be interpreted alongside the primary analysis rather than used to replace it.

The registry reports 11 outcome measures and 40 analyses, while one secondary endpoint is listed in the posted secondary results. The record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting secondary outcomes. When many outcomes or analyses are examined, the chance of at least one apparently favorable result can increase even if there is no underlying effect. General statistical practice therefore gives less weight to unadjusted secondary findings than to a prespecified primary outcome, especially when the multiplicity strategy is not reported.

The available secondary result does not establish how other outcomes behaved, and no broad claim about all secondary endpoints is warranted from one posted result. The registry record does not report whether the secondary analysis was adjusted for the primary analysis, whether it was considered confirmatory, or what rules governed interpretation across outcomes.

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

• Change From Baseline to Week 65 in Composite UHDRS (cUHDRS) Total Score (mITT)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference represent?

The primary endpoint is continuous: it is a score measured on a numerical scale. For a continuous outcome, a group mean summarizes the average score change among participants included in the analysis. The difference between group means expresses how far apart those average changes are, with its sign determined by the order of subtraction. In the posted primary comparison, the listed estimate is for pridopidine relative to placebo. A negative estimate means the estimated change was more negative in the pridopidine group. Because the scale assigns lower scores to greater impairment, the direction can be described mathematically, but the estimate alone does not establish a clinically important effect.

The least-squares means in the registry are model-based averages rather than necessarily simple arithmetic averages. In general, a model can estimate group means while accounting for the structure specified in its analysis. The record identifies the sponsor's primary comparison method as Mixed Models Analysis, but the model specification, included covariates, covariance structure, and handling of incomplete repeated measurements are not reported in the registry record.

What does the standard error tell the reader?

A standard error describes uncertainty in an estimated mean. It is not the spread of individual participant outcomes. Individual outcomes can vary substantially even when a mean is estimated with some precision. The posted standard errors for the primary group means are 0.119 for each group. They should be read as uncertainty measures for the corresponding estimated averages, not as score ranges for participants.

In general, standard errors contribute to confidence intervals and test statistics. A smaller standard error usually indicates a more precise estimate, all else being equal. Precision depends on features such as outcome variability and the amount of information in the analysis. The registry record does not report enough detail to reconstruct the sponsor's model-based standard errors independently from the posted summary statistics.

How should the confidence interval and p-value be read?

A confidence interval gives a range of values compatible with the data and the assumptions of the analysis at a stated confidence level. The sponsor reports a 95% confidence interval for the primary mean difference, from -0.54 to 0.09. Because zero lies within this interval, the result is compatible both with no group difference and with differences in either direction within the interval. The interval's endpoints describe uncertainty in the group contrast; they are not a range containing a fixed proportion of individual outcomes.

The p-value is a measure of how unusual the observed result, or a more extreme result, would be under the null hypothesis and the analysis assumptions. The sponsor's primary p-value is 0.167. It is not the probability that the null hypothesis is true, nor does it measure the probability that treatment is beneficial or harmful. A p-value above 0.05 does not prove equality. It indicates that the primary comparison did not meet that conventional significance threshold in the reported analysis.

Why can the recalculation differ from the sponsor's model?

The simple recalculation uses the posted group-level summaries and is explicitly unadjusted. It gives a mean difference of -0.23 and an unadjusted p-value of 0.172. The sponsor's reported mixed models analysis gives -0.22 and p = 0.167. Small differences between estimates or p-values can arise because a summary-statistic calculation does not necessarily use the same information or assumptions as a model-based analysis. The registry record does not provide the full model specification needed to reproduce the sponsor's calculation. The reported sponsor analysis is therefore the appropriate reference for the trial's own primary result.

The recalculation uses an approximate pooled standard deviation of 1.863, derived from the posted standard errors and group sizes. This is a working approximation for the unadjusted calculation, not a reported measure of the outcome's variability from participant-level data. The record's model-based standard errors for the group means and its model-based comparison should not be treated as interchangeable with that approximation.

Why can over-dispersion matter in general?

General statistical context: some outcomes vary more than a simple model assumes. When the actual variability exceeds the assumed variability, standard errors can be too small if that extra variation is ignored. That can make confidence intervals too narrow and p-values too optimistic. This issue is especially relevant for outcomes such as counts, where a basic model may assume a variance tied closely to the mean. The primary endpoint is a continuous score, and the record does not report an over-dispersion analysis for it. The general principle should not be mistaken for a finding about this trial.

For continuous outcomes, model assumptions about residual variation, distribution, and repeated measurements can also affect uncertainty estimates. The record names a mixed models method but does not report diagnostic checks or alternative analyses. These omissions limit independent assessment of the model assumptions; they do not, by themselves, show that the analysis is invalid.

11. Confidence Intervals and Precision

The sponsor's primary estimate is a mean difference of -0.22, with a 95% confidence interval from -0.54 to 0.09. The interval includes zero and spans estimates favoring either direction under the comparison's coding. It indicates meaningful uncertainty around the point estimate: the observed estimate should not be read as the only value compatible with the data. The reported p-value, 0.167, is consistent with the confidence interval crossing zero under a conventional two-sided test.

The confidence interval is more informative than a binary label of statistically significant or not statistically significant because it conveys a range of plausible group differences under the analysis assumptions. It does not say that every value inside the interval is equally likely, and it does not describe the distribution of individual score changes. Nor does its inclusion of zero prove that there is no effect. It indicates that the data do not rule out zero at the stated confidence level, while also allowing for nonzero differences within the interval.

The simple unadjusted re-calculation yields -0.23 with a p-value of 0.172; its recalculated interval is not quoted because the underlying summary-based interval has more decimal places than the reporting limit allows. The sponsor's interval is the relevant model-based precision estimate for the reported primary analysis. The registry record does not give a minimally important difference for the endpoint, so the clinical importance of values across the interval cannot be judged from the posted results alone.

Precision is distinct from the direction of the estimate. A point estimate can be negative while remaining uncertain about whether the underlying group difference is negative, zero, or positive. The posted estimate should therefore be read together with its confidence interval, the model used, and the outcome's scale, rather than as a stand-alone conclusion.

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 planning figures are participants per arm, not total participants or total events. They are illustrative calculations based on the observed effect, rather than the trial's original design justification. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the number of participants per arm estimated to be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect and the other assumptions hold. The 90% power column gives the corresponding planning number for a 90% chance. Power is a design-stage probability under specified assumptions, not a guarantee that a study will detect an effect and not a probability that a particular result is correct.

The planning display gives figures for detecting 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For the primary comparison, the per-arm figures are 1,030 and 1,379 for 100% of the observed effect; 1,831 and 2,451 for 75%; and 4,119 and 5,514 for 50%, for 80% and 90% power respectively. Smaller effects require more participants under these assumptions because they are harder to distinguish from random variation. These are planning illustrations, not observed power.

The calculations are not a retrospective judgment that the trial was designed appropriately or inadequately. They rely on the observed effect, which is itself uncertain, and on simplified assumptions. The registry record does not report whether the original planning used the same effect, allocation, significance level, approximation, or outcome model.

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 = -0.230; pooled standard deviation σ = 1.863.
2. n = 2 × (1.96 + 0.842)² × 1.863² / -0.230² = 1,029.6, rounded up to 1,030 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 <- -0.23                      # observed difference in means
sigma <- 1.86270694086348                     # 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(4556656)
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 = 1,030 (80% power), 1,379 (90% power)
 75% of observed effect: n per arm = 1,831 (80% power), 2,451 (90% power)
 50% of observed effect: n per arm = 4,119 (80% power), 5,514 (90% power)
power.t.test: 1030.6 
Simulated power at n = 1,030 per arm: 0.801 (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 sponsor's own primary analysis is a Mixed Models Analysis of the mean difference in final values. It reports -0.22, a 95% confidence interval from -0.54 to 0.09, and p = 0.167. This is the trial's reported analysis and should take precedence over a simple recalculation from posted summary statistics.

The unadjusted recalculation estimates a mean difference of -0.23 and gives p = 0.172. Those results are close to the sponsor's estimate and p-value. The small numerical difference does not change the broad reading: both analyses give a negative point estimate, and neither supports a statistically clear difference at the conventional 0.05 threshold. The sponsor's model-based interval includes zero.

The recalculation is not a replication of the sponsor's model. It uses summary values and an approximate pooled standard deviation, without access to participant-level observations or the full model specification. The registry record does not report sufficient detail to determine exactly which modeling choices account for the difference. The sponsor's analysis is not marked as discrepant from the recalculation in the record, but agreement in broad direction does not make the methods identical.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study tests more than one outcome, timepoint, subgroup, or analysis. In general, conducting many tests can increase the chance of a nominally positive result arising by chance. A protocol may address this through a prespecified testing sequence, an adjustment to significance thresholds, or another strategy that controls the overall error rate. The registry record reports 11 outcome measures and 40 analyses, but the multiplicity strategy is not reported in the registry record.

The primary outcome is identified as change in Total Functional Capacity from baseline to Week 65. The record also lists Composite UHDRS total score change as a secondary outcome. It does not report the full analysis hierarchy, whether secondary outcomes were confirmatory or exploratory, or whether the sponsor adjusted their p-values or confidence intervals for multiple comparisons. Accordingly, the secondary p-value should not be interpreted as if it were necessarily a stand-alone confirmatory test.

Missing-data methods are also important in a repeated-measures trial. The primary analysis population excludes participants without the required baseline and post-baseline in-clinic TFC scores, according to the registry's description of the modified intent-to-treat population. The record says the population was analyzed according to treatment to whi—; the remainder of that sentence is not reported in the registry record. The full missing-data assumptions, imputation methods, sensitivity analyses, and reasons for missing outcome measurements are not reported.

The modified intent-to-treat population is described as participants in the intent-to-treat population who received at least one dose and had valid in-clinic TFC scores at baseline and at least one post-baseline timepoint. This definition is narrower than a population including every randomized participant, because it requires treatment exposure and usable outcome measurements. The record does not provide enough information to assess the effect of those requirements or to compare the analysis population with all randomized participants.

The absence of reported details does not show that multiplicity or missingness was mishandled. It means readers cannot verify from the registry record which safeguards and sensitivity checks were used. Those details matter when judging how robust the conclusions are to analytic choices.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: acute myocardial infarction (1.2%), suicide attempt (1.2%), suicidal ideation (0.8%), anxiety (0.8%), fall (0.8%).

The registry reports serious adverse events affecting 34 participants in the pridopidine group and 21 in the placebo group. The corresponding groups at risk are reported as 250 and 249. Deaths are reported as 4 in the pridopidine group and 1 in the placebo group. These are descriptive counts in the registry record; they do not establish that treatment caused or prevented any event.

The most frequent serious-event terms listed include acute myocardial infarction and suicide attempt, each at 1.2%, and suicidal ideation, anxiety, fall, and syncope, each at 0.8%. These are registry-reported percentages for the listed terms. Serious adverse events can include events with differing causes, severity, and relationship to treatment. The record does not provide causal assessments for these figures in the information.

Safety counts need to be interpreted with the study population, follow-up, event definitions, and exposure time in mind. The registry record does not report enough detail to compare event timing, duration, recurrence, or treatment attribution. Counts alone cannot determine comparative risk or establish a safety profile. They should be read as adverse-event reporting, not as proof of causation.

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

The primary result is an estimate of the average difference between randomized groups in change in functional capacity from baseline to Week 65. The sponsor reports a mean difference of -0.22, with a 95% confidence interval from -0.54 to 0.09 and p = 0.167. The interval includes zero, so the analysis does not provide a statistically clear difference at the conventional 0.05 threshold. The observed point estimate is negative, but it is uncertain and should not be interpreted alone.

This result does not prove that pridopidine and placebo have identical effects. A confidence interval that includes zero can still be compatible with nonzero differences. It also does not establish that a difference, if present, would be important to participants. The registry record does not report a threshold for clinical importance on the TFC scale, and a group-average score change does not reveal the experience of each participant.

The reported endpoint concerns a defined timepoint and analysis population. It does not by itself answer questions about outcomes beyond Week 65, all participants who may have been randomized, or outcomes not posted in the registry record. The modified intent-to-treat definition requires treatment exposure and valid scores, and the record does not provide the full missing-data procedures needed to evaluate how participants without usable measurements were handled.

Nor should the secondary result be treated as independent confirmation. It also has a confidence interval that includes zero, and the record does not report the multiplicity approach. The safety counts are descriptive and do not establish causal relationships. Taken together, the posted results describe uncertainty in the primary comparison and do not justify a categorical claim about treatment efficacy or absence of effect.

Statistical interpretation is not medical advice. Decisions about care require clinical judgment and information beyond this registry comparison.

18. Why This Trial Matters Statistically

This trial is statistically informative because it tests a clearly defined functional outcome in a randomized, placebo-controlled Phase 3 design. The endpoint uses a scale with an explicit range and interpretation, and the registry identifies the primary timepoint and analysis population. Those features help readers understand what contrast the primary estimate is intended to represent.

The result also illustrates why point estimates and uncertainty should be read together. The estimated primary difference is negative, but the sponsor's confidence interval includes zero and the p-value is 0.167. A conclusion based only on the sign of the estimate would overlook uncertainty; a conclusion based only on a significance threshold would overlook the range of differences compatible with the data.

There is also a useful distinction between a trial's reported analysis and a summary-statistic recalculation. The two primary estimates are close, but the recalculation is unadjusted and does not reproduce the mixed models analysis. The sponsor's analysis is the appropriate reference for the trial result, while a recalculation can help readers understand how the posted group summaries relate to a simple contrast.

Finally, the record shows why reporting detail matters. Multiplicity procedures, the complete analysis specification, missing-data methods, and original sample-size assumptions are not reported in the information available. These omissions do not invalidate the reported results, but they constrain independent assessment of robustness and the strength of secondary evidence. Clear reporting of such choices is essential for interpreting clinical trial estimates responsibly.

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.

Interpretation is limited by the registry record's level of statistical detail. It names a mixed models analysis for the primary comparison but does not report the model specification, included covariates, covariance structure, or diagnostic checks. The sponsor's model-based result can be described, but it cannot be fully reproduced from the posted summary statistics.

The modified intent-to-treat population requires receipt of at least one dose and valid in-clinic TFC scores at baseline and at least one post-baseline timepoint. The record does not report the complete population flow, reasons for missing scores, missing-data assumptions, imputation approach, or sensitivity analyses. These details are needed to assess how the analyzed population and missing outcomes may affect interpretation.

The record does not report the multiplicity strategy, despite listing multiple outcome measures and analyses. It also does not report the original sample-size justification or planned interim analyses. The planning figures associated with the observed effect are illustrative and cannot substitute for the trial's original design assumptions.

Only one secondary endpoint is posted in the registry results. Its result cannot stand in for unposted outcomes or support a general conclusion about all secondary measures. The record also does not provide a minimally important difference for the primary scale, limiting assessment of clinical importance from the group contrast alone.

Finally, adverse-event counts are descriptive. The information reported does not establish event attribution, timing, or comparative exposure-adjusted risk. These limitations concern what can be concluded from the registry record; they do not demonstrate that unreported analyses were not performed.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: PRidopidine's Outcome On Function in Huntington Disease, PROOF- HD — NCT04556656.
• Registry record last updated 2025-03-12; status last verified 2025-02.
• Results first posted 2025-03-12.
• 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

NCT04556656 is a completed, randomized, quadruple-masked, parallel-arm Phase 3 study of pridopidine versus matching placebo in early-stage Huntington disease. The active regimen was 45 mg twice daily. The primary endpoint was change in UHDRS Total Functional Capacity from baseline to Week 65 in the modified intent-to-treat population.

The sponsor's primary analysis reported a mean difference of -0.22, with a 95% confidence interval from -0.54 to 0.09 and p = 0.167. The interval includes zero, and the posted analysis does not show a statistically clear group difference at the conventional 0.05 threshold. The registry lists a Composite UHDRS change measure as a secondary outcome; its reported confidence interval also includes zero.

The record reports serious adverse-event counts and deaths by group. It does not report the multiplicity strategy, complete missing-data methods, full model specification, or original sample-size justification in the information. Those omissions limit independent assessment of analytic robustness and secondary findings.