First Time Use of SD-809 in Huntington Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for First Time Use of SD-809 in Huntington Disease (NCT01795859), a randomized phase 3 study. The primary outcome is Change From Baseline (Average of Screening and Day 0) in the Average TMC Scores From Weeks 9 & 12.

2. Clinical Question

The trial was intended to assess SD-809 tablets for chorea associated with Huntington disease. Its primary outcome was a continuous score, so the central comparison concerns the amount of change in the score rather than the number of participants meeting a responder threshold. The registry reports group estimates and an adjusted comparison for that outcome.

The TMC score sums chorea scores on a scale ranging from 0-28. The primary comparison is therefore interpretable in the scale’s units: more negative change represents a greater decrease in the score. The registry’s results describe the observed group estimates and their uncertainty; they do not establish whether a particular score change is clinically important, because a threshold for clinical importance is not reported in the registry record.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase 3 study titled First Time Use of SD-809 in Huntington Disease. Its official title describes a randomized, double-blind, placebo-controlled study of SD-809 extended release for chorea associated with Huntington disease. The sponsor was Teva Branded Pharmaceutical Products R&D, Inc.

The registry reports enrollment of 90. Participants were assigned to SD-809 tablets or placebo; each reported primary-outcome group has 45.0 participants. The record marks the study as completed. Its start date is 2013-08-05 and its primary completion date is 2014-12-05. These dates describe the registered study timeline and do not, by themselves, provide information about the timing of analyses or the duration of follow-up for every participant.

The intervention description identifies SD-809 extended-release tablets in 6, 9 and 12 mg strengths, taken three times a day. It also describes the final 6 mg dose as placebo. The placebo is listed as the comparator intervention. The record does not report the actual dose each participant received over time, adherence, or details of any dose adjustments, so those aspects cannot be characterized from the registry information.

Randomization is intended, in general, to reduce systematic differences between groups at the point of assignment. Masking is intended, in general, to limit the influence of treatment knowledge on participant experience, care, and outcome assessment. The registry identifies quadruple masking but does not specify the four roles masked. The precise randomization procedure, allocation concealment method, and original sample-size justification are not reported in the registry record.

The study’s stated purpose was to determine whether SD-809 tablets are effective in treating chorea associated with Huntington disease. The statistical results address measured outcomes in the trial; they do not by themselves answer questions about longer-term outcomes or populations not described in this 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The Modified ITT (mITT) Population was defined as all subjects in the ITT Population who received study drug and had at least one postbaseline assessment. For subjects who missed both Week 9 or Week 12 scores, the last available assessment was used

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 (Average of Screening and Day 0) in the Average TMC Scores From Weeks 9 & 12, measured over Screening, Day 0, Weeks 9, 12.

The primary endpoint was change from baseline in the average TMC scores from Weeks 9 and 12. Baseline was defined as the average of Screening and Day 0. TMC is a continuous measure: the total score is the sum of chorea scores on a scale ranging from 0-28, and a decrease indicates improvement in chorea.

A continuous score retains information about the size and direction of measured changes rather than reducing each participant’s result to a yes-or-no category. Comparing average change between randomized groups can therefore describe the difference in the amount of score change over the assessment period. The endpoint’s repeated assessment at Weeks 9 and 12 is reflected in the average used for the primary outcome; it should not be read as two separate primary results.

The registry reports least-squares means for the groups and a least-squares mean difference from an ANCOVA analysis. Least-squares means are model-based group estimates, rather than simple raw averages. The registry also defines the primary analysis population as participants in the intention-to-treat population who received study drug and had at least one postbaseline assessment. For participants missing both Week 9 and Week 12 scores, the last available assessment was used.

This outcome was selected to quantify change in chorea using a score directly related to the condition under study. The registry does not report a threshold that would define a clinically important change, so the numerical difference should be interpreted as a difference in score units, not as proof of a specified level of benefit.

7. Results Posted in the Registry

• SD-809 Tablets: mean -4.42 versus -1.93 on control; difference -2.49 (95% CI -3.65 to -1.33), standardized effect d = -0.89; 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.

Number of Participants With Treatment Success at the End of Therapy as Measured by the Patient Global Impression of Change (PGIC)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • SD-809 Tablets: 51.1% (23/45) versus 20.0% (9/45) on control; risk difference 31.1 percentage points (95% CI 12.4 to 49.8), risk ratio 2.56 (1.33–4.90); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for SD-809 Tablets than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants With Treatment Success at the End of Therapy Based on Clinical Global Impression of Change (CGIC)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • SD-809 Tablets: 42.2% (19/45) versus 13.3% (6/45) on control; risk difference 28.9 percentage points (95% CI 11.4 to 46.4), risk ratio 3.17 (1.40–7.19); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for SD-809 Tablets than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in the Short Form 36 Health Survey (SF-36) Physical Functioning Score (Based on Items 3a to 3j) From Baseline to Week 12

• 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:
  • SD-809 Tablets: mean 0.74 versus -3.61 on control; difference 4.35 (95% CI 0.29 to 8.41), standardized effect d = 0.45; z-test p = 0.036.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for SD-809 Tablets than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary results cover participant-rated treatment success, clinician-rated treatment success, physical functioning, and balance. Among the secondary results with numerical estimates posted, the numerical pattern generally favors SD-809 in the direction of more participants classified as successful or a more favorable average physical-functioning change. The balance outcome is listed among the secondary outcomes, but its result is not reported in the registry record.

These outcomes complement the primary TMC result by addressing different aspects of change: perceptions of overall improvement, physical functioning, and balance rather than the primary chorea score alone. Agreement in direction across measures can be informative, but secondary outcomes do not independently establish the primary finding or determine whether changes are clinically meaningful. They also differ in scale and analysis, so their effect estimates should not be compared as if they measured the same quantity.

Each secondary result has its own uncertainty and analysis. The registry reports unadjusted p-values for the posted secondary comparisons, as well as its own reported analyses. When several outcomes are tested, the chance of at least one apparently notable finding can rise if no multiplicity adjustment is used. The registry record does not report an adjustment procedure, a hierarchy of hypotheses, or a prespecified strategy for interpreting the secondary outcomes. Their results therefore carry less confirmatory weight than a single primary outcome tested under a documented plan.

The number of participants contributing data can also differ by outcome. The physical-functioning comparison reports 45.0 participants in the SD-809 group and 43.0 in the placebo group. Reasons for the difference in available outcome data and the missing-data handling for secondary measures are not reported in the registry record. These gaps limit direct evaluation of whether missing observations could affect the pattern of secondary estimates.

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

• Number of Participants With Treatment Success at the End of Therapy as Measured by the Patient Global Impression of Change (PGIC)
• Number of Participants With Treatment Success at the End of Therapy Based on Clinical Global Impression of Change (CGIC)
• Change in the Short Form 36 Health Survey (SF-36) Physical Functioning Score (Based on Items 3a to 3j) From Baseline to Week 12
• Change in Berg Balance Test (BBT)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary comparison is an analysis of a continuous outcome. In general, a continuous measure can take a range of values, and a group mean summarizes its central tendency. The primary endpoint is change in TMC score, so its group estimates describe average changes from baseline rather than final scores alone. A negative change indicates a decrease in TMC score, which the registry describes as indicating improvement in chorea.

What does the adjusted analysis estimate?

The registry reports an ANCOVA analysis with a least-squares mean difference. In general, analysis of covariance estimates a group contrast while accounting for covariates included in the model. A least-squares mean is a model-based estimate, typically adjusted for the model’s specified terms; it is not automatically identical to a raw group average. The covariates, model specification, and handling of assumptions for the registry’s ANCOVA are not reported in the registry record. Therefore, the adjusted result can be described as the registry’s reported analysis, but its exact adjustment cannot be reconstructed from the posted information.

The primary result is also accompanied by a recalculated unadjusted difference based on the posted group summary statistics. In general, an unadjusted contrast uses the available group summaries without reproducing an adjustment model. It provides a useful check on the direction and approximate magnitude of the reported comparison, but it is not a replacement for the sponsor’s prespecified or model-based analysis. The discrepancy flag is false, and the sponsor’s result is close to the recalculation.

How should the p-value be understood?

In general, a p-value describes how incompatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The primary registry analysis reports p < 0.001, while the recalculation reports p < 0.001. These are both small p-values, but their interpretation remains conditional on the analysis methods and assumptions. The registry does not report whether the primary hypothesis or analysis was prespecified in a detailed statistical analysis plan.

Randomized allocation helps make a between-group comparison meaningful by assigning participants without relying on clinician or participant selection of treatment. In general, randomization does not ensure that every characteristic is exactly balanced, particularly in a study with a limited number of participants. The baseline characteristics and details of the randomization procedure are not reported in the registry record, so balance and implementation cannot be evaluated from these results alone.

What is the role of the confidence interval?

In general, a confidence interval presents a range of values compatible with the data and method at a stated confidence level. It conveys both the estimated direction and the precision of a comparison. The registry reports a 95% interval for the primary least-squares mean difference, from -3.69 to -1.29. The recalculated 95% interval is from -3.652 to -1.328. The intervals are close but not identical because one comes from the registry’s ANCOVA model and the other from an unadjusted summary-statistic calculation.

For a mean difference, zero represents no difference between the compared group means on the scale of the measure. In general, an interval that does not include zero is evidence against a zero difference under the interval’s method and assumptions. This statistical interpretation does not supply a clinical-importance threshold. Such a threshold, along with the protocol’s rationale for the selected endpoint, is not reported in the registry record.

Why can group variability matter?

In general, standard deviations describe the spread of individual measurements around a group mean. Greater variability can make a group mean difference less precisely estimated, while lower variability can make the same difference more precise, all else being equal. The primary group standard deviations are 2.953 for SD-809 tablets and 2.666 for placebo. These summarize observed spread, not uncertainty in the group mean itself. The recalculation uses a pooled standard deviation of 2.813 and reports an approximate standardized effect size of -0.885. A standardized effect expresses a difference relative to a measure of variability; it does not replace interpretation in TMC score units.

Some recalculated standard errors are marked approximate. In general, a standard error estimates the variability of an estimator across repeated samples under a statistical model. It is used to describe precision and to form inferential quantities such as confidence intervals. Approximation means the calculation relies on simplifying assumptions or summary-statistic methods; it should not be mistaken for a reproduction of participant-level analysis. The detailed calculation procedure and underlying participant-level data are not reported in the registry record.

What can be inferred from the secondary analyses?

Binary secondary outcomes count participants classified as treatment successes, while the physical-functioning measure is continuous. In general, a risk difference expresses a difference in proportions between groups, whereas a mean difference expresses a difference in average scale values. These quantities have different units and should not be compared by magnitude alone. The registry also reports model-based results for the physical-functioning outcome.

The posted secondary analyses include unadjusted comparisons and p-values. In general, testing several outcomes increases the chance that at least one result may appear statistically notable by chance if no adjustment is made. A multiplicity procedure may control that issue, but the registry record does not report one. Secondary p-values should therefore be viewed as exploratory or supportive unless a prespecified testing strategy is documented; no such strategy is reported in the registry record.

These methods explain the scope of the posted estimates, not every choice made in the original trial analysis. The full statistical analysis plan, covariate list, detailed model diagnostics, and protocol-level analysis assumptions are not reported in the registry record.

11. Confidence Intervals and Precision

The primary registry analysis estimates a least-squares mean difference of -2.49 TMC score units, with a 95% confidence interval from -3.69 to -1.29. The unadjusted recalculation also estimates -2.49, with a 95% confidence interval from -3.652 to -1.328. Both intervals fall below zero, consistent with a greater decrease in the SD-809 group under the direction of the comparison used. Their slightly different limits reflect the distinction between the registry’s adjusted ANCOVA analysis and a recalculation from summary statistics.

In general, the width of a confidence interval conveys precision: narrower intervals indicate a more tightly estimated value under the method, while wider intervals allow a broader range of compatible values. An interval is not a guarantee that the true effect lies within its limits, and its coverage interpretation depends on the statistical assumptions and procedure. A confidence interval also does not indicate whether an effect is clinically important. The registry record does not report a threshold for a meaningful TMC score change.

The primary interval gives information about the average group contrast, not the range of individual responses. Individual participants may have changes above or below the group averages. The group standard deviations describe variability among observations, while the confidence interval describes uncertainty about the estimated group difference; these are distinct quantities.

Precision should also be interpreted in the context of the analysis population and missing data. The primary analysis included participants in the defined modified intention-to-treat population who received study drug and had at least one postbaseline assessment. For participants missing both Week 9 and Week 12 scores, the last available assessment was used. The number affected by that rule and the amount of missing information are not reported in the registry record, limiting assessment of how missingness may relate to the estimated precision.

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 estimates are planning illustrations based on the observed effect, not the original design assumptions for this trial. The estimates are participants per arm for the continuous and binary outcomes; they are not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For time-to-event outcomes, the stated convention would be total events, but the posted outcomes are not time-to-event outcomes.

The 80% power column describes the estimated number of participants per arm for a hypothetical study to have an 80% chance of detecting the selected effect under the planning assumptions, if that effect is real and the assumptions hold. The 90% power column describes the corresponding planning target for a 90% chance. These are design calculations, not a probability that the observed trial result is correct and not a measure of the probability that treatment is effective.

Each row uses a different fraction of the observed effect as the effect to detect. Planning for 75% of the observed effect requires more participants than planning for the full observed effect; planning for 50% requires still more. This illustrates the general relationship: smaller effects are harder to distinguish from random variation and need more participants for a given power target, all else being equal.

These figures are not observed power. They are conditional planning estimates derived from the observed effects and the stated assumptions. The trial’s original sample-size justification, design effect assumption, and any original power calculation are not reported in the registry record. The estimates should therefore be read as illustrations of how design targets change when the assumed effect changes, not as evidence that the completed study was adequately or inadequately sized.

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 = -2.490; pooled standard deviation σ = 2.813.
2. n = 2 × (1.96 + 0.842)² × 2.813² / -2.490² = 20.0, 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 <- -2.49                      # observed difference in means
sigma <- 2.81316236644812                     # 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(1795859)
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), 27 (90% power)
 75% of observed effect: n per arm = 36 (80% power), 48 (90% power)
 50% of observed effect: n per arm = 81 (80% power), 108 (90% power)
power.t.test: 21 
Simulated power at n = 21 per arm: 0.798 (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 primary analysis used ANCOVA and reported a least-squares mean difference of -2.49, with a 95% confidence interval from -3.69 to -1.29 and p < 0.001. The recalculation from posted group summaries gives an unadjusted mean difference of -2.49, with a 95% confidence interval from -3.652 to -1.328 and p < 0.001. Both analyses indicate a negative difference in the comparison’s stated direction, and their estimates are close.

The registry analysis and the recalculation are not interchangeable. ANCOVA is model-based and may account for covariates, while the recalculation uses summary statistics and is unadjusted. The registry does not report the ANCOVA covariates or full model specification, so the adjusted estimate cannot be independently reconstructed from the summary information. Small differences in confidence limits and p-values are therefore unsurprising.

The discrepancy indicator is false, and the estimates do not show a substantive disagreement in the reported direction or point estimate. The sponsor’s own analysis remains the relevant reported trial analysis; a recalculation is a transparent comparison based on summary statistics, not a substitute for participant-level analysis or the original statistical analysis plan.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and several secondary outcomes, but it does not report whether the analysis plan used a multiplicity adjustment. In general, multiplicity arises when several hypotheses are tested: even if each test uses a conventional significance threshold, the chance of at least one false-positive result across the set can increase. Common approaches include adjusting thresholds or organizing hypotheses in a prespecified sequence. Whether any such strategy was planned or used is not reported in the registry record.

The primary finding should be distinguished from the secondary findings for this reason. The registry reports a primary ANCOVA result and separate secondary analyses, but the record does not describe a formal hierarchy that would define which secondary tests, if any, were confirmatory. The unadjusted secondary p-values may be useful as descriptive evidence, but they should not be interpreted as if they had been protected against multiplicity.

Missing-data information is also incomplete. For the primary outcome, the modified intention-to-treat population is defined as participants in the intention-to-treat population who received study drug and had at least one postbaseline assessment. If a participant missed both Week 9 and Week 12 scores, the last available assessment was used. The registry does not report the number of participants for whom this rule was applied, the amount or pattern of missing primary data, or sensitivity analyses using alternative assumptions.

The registry does not state the analysis populations used for each secondary outcome or describe how missing secondary measurements were handled. The full statistical analysis plan, the original sample-size justification, and details of interim analyses are not reported in the registry record. It is therefore not possible to determine from the registry alone whether every analysis followed a prespecified plan or how robust the results are to alternative missing-data assumptions.

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: cholecystitis chronic (2.2%), agitated depression (2.2%), chronic obstructive pulmonary disease (2.2%).

The registry reports serious adverse events for both groups: 1 participant in the placebo group and 1 participant in the SD-809 group, with 45 participants at risk in each group. It also reports other adverse events for 21 participants in the placebo group and 18 participants in the SD-809 group, again with 45 participants at risk in each group. These are descriptive counts from the registry record.

The serious-event terms listed as top terms are Cholecystitis chronic, Agitated depression, and Chronic obstructive pulmonary disease, each reported as 2.2%. The record does not assign these terms to a specific treatment group in the listed summary. Deaths are not reported in the registry record.

Counts alone do not show whether events were caused by treatment, how severe non-serious events were, or whether the groups had comparable exposure and follow-up. The summary also does not establish equivalence or rule out uncommon harms. A fuller safety interpretation would require event definitions, timing, exposure information, and detail about the circumstances of each event, which are not reported in the registry record.

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

The primary result describes a difference in average change in TMC score between SD-809 tablets and placebo over the assessed period. The registry’s adjusted estimate is -2.49, and the reported 95% confidence interval is from -3.69 to -1.29. The point estimate and interval indicate that the average change favored a greater decrease in TMC score in the SD-809 group under the registry’s comparison. The result is statistically precise enough to place the reported interval below zero under the stated analysis, but statistical evidence is not the same as proof of clinical importance.

The outcome is a score for chorea, and the registry states that a decrease indicates improvement. However, the registry does not report a threshold that defines an important change for participants, nor does it report how the score difference relates to daily functioning or longer-term outcomes. The numerical result should therefore be interpreted in its measured units and within the duration and population studied, not translated into a broader claim about the experience of every participant.

The result also does not establish that every participant’s score improved. Group means can conceal variation in individual responses, and the primary standard deviations indicate that participants’ changes were spread around those averages. The available summaries do not describe the distribution of individual changes or the proportion meeting a clinically defined response threshold for the primary outcome.

Secondary outcomes and adverse-event counts provide additional context but have their own limitations. Secondary findings are subject to uncertainty and possible multiplicity, while the safety summary is descriptive and does not establish causation. Missing-data details, the full analysis plan, and clinical-importance thresholds are not reported in the registry record.

Accordingly, the registry supports a statistical description of the measured primary comparison in this completed trial. It does not, by itself, establish how durable the observed difference is, how it applies beyond the studied participants and assessment period, or what treatment choice is appropriate for any individual.

18. Why This Trial Matters Statistically

This trial illustrates why interpreting a clinical result requires more than reading a p-value. The primary outcome is a continuous chorea score, and the registry reports both the estimated group difference and its confidence interval. Together, these quantities show the direction and scale of the measured contrast and how precisely it was estimated under the analysis method.

It also illustrates the distinction between a sponsor-reported adjusted analysis and an unadjusted recalculation from summary statistics. The point estimates are close, while confidence limits and p-values are not identical. That distinction matters because adjusted and unadjusted analyses answer related but not necessarily identical questions. Summary statistics allow a useful consistency check, but do not reproduce a participant-level model whose full specification is not reported.

The registry’s secondary outcomes show why a set of related results needs a clear interpretation plan. Outcomes can measure different experiences and functions, and testing multiple outcomes without a reported multiplicity strategy makes individual secondary p-values less conclusive. Missing-data rules and analysis populations also matter: the primary analysis used a defined modified intention-to-treat population and a last-available-assessment rule for a specified missing-score situation, while other details are not reported.

Finally, sample-size illustrations based on observed effects should not be confused with the trial’s original design rationale or with observed power. They can help explain how smaller target effects require larger planned samples under stated assumptions. They cannot establish whether the original design was adequate when the original assumptions are not reported in the registry record.

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.

Several trial-specific details needed for a fuller statistical assessment are not reported in the registry record. The randomization sequence, allocation concealment, masked roles, baseline characteristics, and treatment adherence are not described in the results information. The record identifies quadruple masking but does not specify which groups of people were masked.

The primary endpoint is reported as an average of Week 9 and Week 12 assessments, with a last-available-assessment rule for participants missing both scores. The number of participants affected, the overall amount and pattern of missing data, and sensitivity analyses are not reported. The registry’s modified intention-to-treat definition also means the exact analysis population cannot be evaluated without participant-flow details.

The ANCOVA result is reported, but the model covariates, diagnostics, and other specifications are not reported in the registry record. The primary estimate can be quoted, but the adjustment cannot be independently reproduced from the group summaries. The full statistical analysis plan and the original sample-size justification are also not reported.

Secondary outcomes have incomplete analysis detail. The registry does not report a multiplicity-control procedure or a formal hierarchy for the secondary hypotheses, and the balance outcome result is not reported in the registry record. Secondary missing-data handling and analysis populations are likewise not described. These omissions limit how strongly the secondary findings can be interpreted as confirmatory.

Finally, a threshold for a clinically important TMC change is not reported. The safety summary provides counts and selected serious-event terms but does not provide detailed event narratives, exposure-adjusted comparisons, or deaths. These limitations constrain interpretation of clinical importance and safety beyond the reported counts.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: First Time Use of SD-809 in Huntington Disease — NCT01795859.
• Registry record last updated 2017-09-20; status last verified 2017-08.
• Results first posted 2017-08-11.
• 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

NCT01795859 is a completed randomized, quadruple-masked, parallel-group phase 3 trial of SD-809 extended release versus placebo for chorea associated with Huntington disease. The registry reports enrollment of 90 and dates of 2013-08-05 for study start and 2014-12-05 for primary completion.

The primary endpoint was change from baseline in average TMC score at Weeks 9 and 12. The registry reports an ANCOVA least-squares mean difference of -2.49, with a 95% confidence interval from -3.69 to -1.29 and p < 0.001. The recalculated unadjusted estimate is also -2.49, with a 95% confidence interval from -3.652 to -1.328 and p < 0.001.

Secondary results are available for participant-rated treatment success, clinician-rated treatment success, and physical functioning; a balance outcome is listed but its result is not reported in the registry record. The registry also reports serious and other adverse-event counts. Multiplicity procedures, several missing-data details, the original sample-size rationale, and a clinical-importance threshold are not reported in the registry record.