Sarizotan in Participants With Parkinson's Disease Suffering From Treatment Associated Dyskinesia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sarizotan in Participants With Parkinson's Disease Suffering From Treatment Associated Dyskinesia (NCT00105521), a randomized phase 3 study. The primary outcome is Change From Baseline in Diary-Based On-Time Without Dyskinesia at Week 12.

2. Clinical Question

The primary measure was recorded in hours per day. It counted periods when participants had no off-time symptoms, were awake, and had no difficulty performing voluntary movements because of dyskinesia. Off-time was defined by increased parkinsonian symptoms, such as immobility or difficulty moving with ease. Participants recorded on-time in a diary.

The registry record identifies the study as a randomized, double-blind, parallel-group Phase III trial. It lists an enrollment of 398. The primary question is dose-specific: the three sarizotan groups are each compared with placebo, rather than being combined into one sarizotan group. The posted primary outcome gives group means and standard deviations for change from baseline, along with unadjusted recalculated comparisons with placebo.

The clinical question is about the measured diary outcome over the stated study period. It does not, by itself, address every aspect of Parkinson’s disease or dyskinesia, and it does not establish how participants’ outcomes might differ beyond the registry’s recorded measures and follow-up.

3. Trial Design

The registry describes a randomized, double-blind, parallel-group Phase III study sponsored by EMD Serono. Its official title describes a multicenter, multinational study. The record lists 398 enrolled participants and a completed status. The listed study start is 2004-09-30, and primary completion is 2006-03-31.

Participants were allocated to placebo or one of three sarizotan daily-dose groups: 2 mg/day, 4 mg/day, or 10 mg/day. Sarizotan was given in two divided daily doses, up to Week 12. Placebo was matched to sarizotan and taken orally twice daily up to Week 12. Randomization and double masking are stated in the record; details of the allocation sequence, concealment, and how masking was maintained are not reported in the registry record.

The primary outcome was change from baseline in diary-based on-time without dyskinesia at Week 12. The primary population was defined as the modified intent-to-treat population, comprising randomized participants who received at least one treatment dose and had at least one follow-up visit assessment for an efficacy target outcome. This is narrower than a definition that includes every randomized participant, because it requires treatment exposure and follow-up assessment.

The registry lists three secondary outcomes: change in the Modified Abnormal Involuntary Movement Scale score, change in the UPDRS Items 32 and 33 composite score, and change in the UPDRS Part III total score, each at Week 12. Results for three secondary outcomes are posted. The original sample-size justification, detailed statistical analysis plan, and protocol-defined approach to missing data are not reported in the registry record. The record also does not list reported analyses for the primary or secondary outcomes, so the comparisons discussed are recalculations from the posted group summaries rather than reported sponsor-model estimates.

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: Modified intent-to-treat (ITT) population included all randomized participants who received at least one treatment dose and who had at least one follow-up visit assessment for an efficacy target outcome.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Diary-Based On-Time Without Dyskinesia at Week 12, measured over Baseline, Week 12.

The primary endpoint is change from baseline in diary-based on-time without dyskinesia at Week 12, measured in hours per day. The diary definition combines several conditions: a participant had no off-time symptoms, was not asleep, and had no difficulty performing voluntary movements due to dyskinesia. Off-time referred to a period of increased parkinsonian symptoms, such as immobility or difficulty moving with ease. Participants recorded on-time in a diary.

Change from baseline expresses how the recorded measure differed at Week 12 from the participant’s baseline value. A positive group mean change indicates an average increase in recorded on-time without dyskinesia over baseline; the comparison with placebo helps describe whether the average changes differed between groups. The outcome is continuous, so the registry reports means and standard deviations rather than event counts.

A diary-based measure captures participants’ recorded experience across time rather than relying only on a single clinic assessment. That can be relevant when the outcome varies during the day. As a general measurement consideration, diary results depend on participants completing and interpreting the diary consistently. The registry record does not report diary-completion rates or additional validation details. Nor does the endpoint alone capture every possible effect of treatment; the other registered outcomes address different scales and aspects of Parkinson’s disease or dyskinesia.

7. Results Posted in the Registry

• Sarizotan 2 mg/Day: mean 1.90 versus 1.60 on control; difference 0.30 (95% CI -0.71 to 1.31), standardized effect d = 0.08; z-test p = 0.560.
• Sarizotan 4 mg/Day: mean 1.70 versus 1.60 on control; difference 0.10 (95% CI -0.80 to 1.00), standardized effect d = 0.03; z-test p = 0.828.
• Sarizotan 10 mg/Day: mean 1.80 versus 1.60 on control; difference 0.20 (95% CI -0.71 to 1.11), standardized effect d = 0.06; z-test p = 0.665.

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 in Unified Parkinson's Disease Rating Scale (UPDRS) Items 32 and 33 Composite Score at 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:
  • Sarizotan 2 mg/Day: mean -1.40 versus -1.00 on control; difference -0.40 (95% CI -0.83 to 0.03), standardized effect d = -0.27; z-test p = 0.066.
  • Sarizotan 4 mg/Day: mean -1.10 versus -1.00 on control; difference -0.10 (95% CI -0.50 to 0.30), standardized effect d = -0.07; z-test p = 0.624.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sarizotan 2 mg/Day and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sarizotan 4 mg/Day and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists three secondary measures at Week 12: change in the UPDRS Items 32 and 33 composite score, change in the Modified Abnormal Involuntary Movement Scale score, and change in UPDRS Part III total score. Results are posted for three secondary outcomes, although the registry record reports no analyses. The posted results therefore require the same distinction as the primary outcome: descriptive group summaries are available, while the inferential comparisons are recalculations rather than reported sponsor analyses.

Across secondary measures, the broad interpretive question is whether they offer a consistent picture alongside the primary diary result. They assess related but distinct aspects of symptoms and functioning, so they need not move in lockstep with diary-based on-time. The primary endpoint comparisons are small in point estimate relative to their uncertainty, and their confidence intervals include zero. Secondary results should be considered as additional context rather than as a substitute for the primary outcome.

Each secondary outcome can generate multiple dose comparisons, and multiple outcomes add further opportunities for chance findings. The registry does not report a multiplicity strategy or adjusted secondary analyses. Unadjusted results therefore carry less weight for confirmatory claims than results from a prespecified analysis that accounts for the family of comparisons. A nominal p-value on one secondary comparison would not, by itself, resolve the overall pattern.

General statistical consideration: secondary endpoints can help assess whether an observed pattern is coherent across measures, but coherence must be judged with attention to measurement differences, uncertainty, and the analysis plan. The record does not provide the protocol’s hierarchy of outcomes, stopping or decision rules, or a prespecified procedure for interpreting secondary tests. Consequently, the secondary results are best treated as descriptive and exploratory evidence within the posted registry information, not as independent confirmation of the primary comparison.

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

• Change From Baseline in Modified Abnormal Involuntary Movement Scale (AIMS) Score at Week 12
• Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Items 32 and 33 Composite Score at Week 12
• Change From Baseline in UPDRS Part III Total Score at Week 12

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant’s change in diary-based on-time without dyskinesia is expressed in hours per day, and the registry reports a mean and standard deviation for each group. A mean describes the group’s average recorded change. A standard deviation describes how spread out individual values are around that mean. It is not the same as the standard error, which describes the precision of an estimated mean.

What does a mean difference describe?

The posted comparisons subtract the placebo mean change from the mean change in each sarizotan group. A positive difference means the active group’s average change was numerically higher than placebo; a negative difference means it was numerically lower. For 2 mg/day, the recalculated difference was 0.3 hours/day; for 4 mg/day, it was 0.1 hours/day; and for 10 mg/day, it was 0.2 hours/day. These are unadjusted comparisons based on the group summaries, not estimates from a reported adjusted model.

Group means are useful for describing average outcomes, but they do not show the full distribution of participant results. The reported standard deviations—3.3 for placebo, 3.8 for 2 mg/day, 3.0 for 4 mg/day, and 3.1 for 10 mg/day—show that values varied across participants. In general, variation among individual outcomes can make a group mean difference less precisely estimated unless the sample contains enough information to narrow the uncertainty.

How should the confidence intervals be read?

A confidence interval gives a range of values reasonably compatible with the data and the calculation’s assumptions. The primary comparisons have 95% confidence intervals: -0.709 to 1.309 hours/day for 2 mg/day, -0.801 to 1.001 hours/day for 4 mg/day, and -0.706 to 1.106 hours/day for 10 mg/day. Because each interval includes zero, the summaries do not isolate a nonzero difference from placebo. The intervals also include values in both directions, so they do not establish that any dose is equivalent to placebo.

Confidence intervals are not guarantees about the true effect, nor do they show the probability that the true effect lies in the observed interval. Their interpretation depends on the statistical method and assumptions used. The registry record does not report a sponsor analysis or its modeling assumptions for these outcomes; the intervals discussed are unadjusted recalculations from posted summaries.

What does an unadjusted p-value say?

A p-value describes how unusual results at least as discrepant as those observed would be under a specified null model and its assumptions. The posted unadjusted values are 0.56, 0.828, and 0.665 for the three dose comparisons. They are not probabilities that the null hypothesis is true, and they do not quantify the size or clinical importance of an effect. A p-value also does not remove uncertainty around the estimate; the confidence interval is useful for seeing the range of compatible differences.

“Unadjusted” matters because the record includes three dose comparisons and multiple outcomes. When many statistical tests are considered, the chance of observing a nominally small p-value by chance can increase. No multiplicity adjustment is reported in the registry record, so these recalculated p-values should be read as individual comparisons rather than as a family-wise analysis.

Why can spread and over-dispersion matter?

For a continuous outcome, large between-participant variation relative to the average difference generally makes it harder to estimate that difference precisely. General statistical explanation: over-dispersion is most often discussed for count data, when observed variability exceeds what a simple count model expects. The primary outcome is continuous rather than a count, so the relevant registry summaries are the standard deviations and confidence intervals, not a count-model over-dispersion parameter. The sizable standard deviations relative to the mean differences help explain why the estimated differences are imprecise.

The reported comparisons use each group’s posted mean, standard deviation, and sample size for a simple two-group calculation. The registry does not report whether the planned sponsor analysis used baseline adjustment, repeated-measures methods, or other model-based techniques. The recalculated results should not be mistaken for those unreported methods or for a reconstruction of the original analysis plan.

The registry identifies the modified intent-to-treat population for the primary outcome. It includes randomized participants who received at least one dose and had at least one follow-up efficacy assessment. General statistical consideration: restricting analysis to participants with some post-baseline information can affect interpretation if the availability of follow-up is related to outcomes or treatment. The record does not report the extent or pattern of missing outcome data, how missing values were handled, or sensitivity analyses. Consequently, the posted summaries cannot answer whether missingness influenced the comparisons.

Finally, statistical evidence and clinical importance are distinct. A mean difference describes the numerical contrast on the endpoint’s scale, while its uncertainty describes precision. The registry record does not state a threshold for a clinically important difference, so the recalculated contrasts cannot be classified against such a threshold from this record alone.

11. Confidence Intervals and Precision

The primary comparisons are imprecise enough to include values both below and above zero. For sarizotan 2 mg/day, the recalculated mean difference was 0.3 hours/day, with a 95% confidence interval from -0.709 to 1.309. For 4 mg/day, it was 0.1 hours/day, with an interval from -0.801 to 1.001. For 10 mg/day, it was 0.2 hours/day, with an interval from -0.706 to 1.106. Each interval includes zero, so the registry summaries do not establish a direction of average difference from placebo.

A confidence interval expresses uncertainty around an estimate under the calculation’s assumptions. In general, narrower intervals indicate greater precision, while wider intervals indicate that a broader range of values remains compatible with the data. These intervals are broad in relation to the point estimates. They do not support a precise estimate of the size of a difference, and they do not demonstrate equivalence. Equivalence would require a prespecified margin and a suitable analysis; no margin is reported in the registry record.

The group standard deviations were 3.3 for placebo, 3.8 for 2 mg/day, 3.0 for 4 mg/day, and 3.1 for 10 mg/day. This variation is substantial relative to the reported mean differences. The primary population sample sizes were 95 for placebo, 96 for 2 mg/day, 93 for 4 mg/day, and 97 for 10 mg/day. The combination of group variability and observed sample sizes is reflected in the uncertainty of the recalculated comparisons.

The intervals are unadjusted recalculations from posted summary statistics. The registry record does not report an inferential sponsor analysis for the primary endpoint, so it is not possible from the record to compare these intervals with intervals from a planned adjusted model. Their precision should be understood as belonging to the simple recalculation, rather than assumed to represent every analysis the trial may have conducted.

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 planning figures are illustrations based on the observed effect, not the trial’s original design calculations. For these continuous outcomes, each figure is the number of participants per arm, not a total across the two groups and not a total number of events. The stated 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 set as the stated fraction of the observed effect. The original trial’s sample-size assumptions are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a planning scenario with an 80% chance of detecting the selected effect under the stated assumptions, if that effect were the true one. The 90% power column gives the corresponding planning figure for a 90% chance. These are prospective planning concepts, not measures of how likely the trial’s observed result was to be correct. For example, for the sarizotan 2 mg/day comparison, planning for 100% of the observed effect gives 2,211 participants per arm for 80% power and 2,960 participants per arm for 90% power.

Rows that plan for 75% or 50% of the observed effect use smaller target differences than the full observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants under the same assumptions. Accordingly, the planning figures rise as the assumed effect becomes smaller. The numbers are illustrations that depend on the observed effect and the listed assumptions; they are not prescriptions for a future study.

This is not observed power. It does not describe the probability that the completed trial detected an effect, and it does not replace interpretation of the estimates and confidence intervals.

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 = 0.300; pooled standard deviation σ = 3.560.
2. n = 2 × (1.96 + 0.842)² × 3.560² / 0.300² = 2,210.7, rounded up to 2,211 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 <- 0.3                      # observed difference in means
sigma <- 3.56011116882486                     # 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(105521)
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 = 2,211 (80% power), 2,960 (90% power)
 75% of observed effect: n per arm = 3,931 (80% power), 5,262 (90% power)
 50% of observed effect: n per arm = 8,843 (80% power), 11,838 (90% power)
power.t.test: 2211.6 
Simulated power at n = 2,211 per arm: 0.796 (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. Multiplicity, Missing Data and Analysis Populations

The registry records a primary outcome and several secondary outcomes, with three sarizotan dose groups compared against placebo. This creates multiple opportunities for statistical testing. The record does not report whether the original analysis used a multiplicity adjustment, a hierarchical testing sequence, or another method to control the chance of false-positive findings across comparisons.

The primary comparisons discussed are unadjusted recalculations. Their p-values are for individual comparisons and do not account for the presence of other doses or endpoints. The registry record lists no reported analyses, and the detailed statistical analysis plan is not reported in the registry record. It is therefore not possible to determine from this record whether the trial’s original analysis treated any comparisons as confirmatory or how it intended to interpret secondary findings.

The primary population is defined as randomized participants who received at least one dose and had at least one follow-up assessment for an efficacy target outcome. The record does not report how many participants lacked a Week 12 measurement, why measurements were missing, or what methods were used to address missing data. It also does not report sensitivity analyses assessing whether assumptions about missing values changed the results. General statistical consideration: when outcome availability is related to participant status or treatment, analysis of observed values alone may not fully represent the randomized groups.

The registry’s population definition and the posted group sample sizes describe who contributed to the primary summaries, but they do not fully explain participant flow or missingness. Details of exclusions after randomization, adherence, and the handling of incomplete diaries are not reported in the registry record. Without those details, the recalculated contrasts cannot establish how robust the results are to different assumptions about missing outcomes.

These reporting gaps limit interpretation of statistical significance and generalizability. They do not prove that a particular method was or was not used outside the registry record; they mean only that the record does not document it.

15. 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

The registry reports serious adverse events among participants at risk in each group. The figures are 5 of 98 for placebo, 8 of 101 for sarizotan 2 mg/day, 7 of 97 for sarizotan 4 mg/day, and 2 of 102 for sarizotan 10 mg/day. These are counts of participants affected and the corresponding group sizes at risk; they are not rates calculated. No top serious adverse event terms are listed in the registry record.

These figures describe the posted serious adverse event counts. They do not establish whether an event was caused by treatment, and they do not by themselves provide a complete comparison of safety. The registry record does not report death counts. It also does not provide event timing, duration, severity details beyond the serious classification, or a narrative account of individual events in the information recorded for this endpoint.

Other adverse events affected 81 of 98 participants in the placebo group, 78 of 101 in the 2 mg/day group, 75 of 97 in the 4 mg/day group, and 85 of 102 in the 10 mg/day group. These are separate counts from the serious-event figures. The registry summaries should be read as descriptive safety information, not as proof of a causal difference between groups.

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

The posted primary outcome shows mean increases from baseline in diary-based on-time without dyskinesia in all four groups: 1.6 hours/day for placebo, 1.9 hours/day for sarizotan 2 mg/day, 1.7 hours/day for 4 mg/day, and 1.8 hours/day for 10 mg/day. The recalculated differences from placebo were 0.3, 0.1, and 0.2 hours/day, respectively. Each 95% confidence interval includes zero and spans values on either side of it. The available summaries therefore leave uncertainty about the direction and size of the average differences.

This does not establish that sarizotan and placebo are equivalent. A failure to distinguish a difference from zero is not the same as demonstrating that any difference is sufficiently small to be unimportant. An equivalence or non-inferiority conclusion would require an appropriate design, prespecified margin, and analysis; the registry record does not report such a margin or analysis.

Nor do these results establish that there is no effect. The confidence intervals include a range of possible differences, and the registry provides no reported sponsor analysis to add model-based context. The point estimates are simple unadjusted recalculations from posted summary data. They describe group averages, not the experience of every participant.

The outcome is specifically diary-recorded on-time without dyskinesia at Week 12. It is not a complete measure of disease status, quality of life, or all potential treatment effects. Secondary scales and safety summaries address other questions, but the record does not report a multiplicity plan or detailed missing-data methods. Those omissions limit how firmly results across outcomes can be combined into a single conclusion.

In general, statistical results are most informative when effect estimates, uncertainty, outcome definitions, and analysis methods are considered together. Here, the registry supports a descriptive account of group changes and unadjusted comparisons, with substantial uncertainty around the differences. It does not, on its own, justify a broad claim about treatment effectiveness or lack of effectiveness.

17. Why This Trial Matters Statistically

This trial is statistically informative because it compares three dose groups separately with a placebo group and reports a continuous, diary-based primary outcome. The design makes the dose-specific contrasts visible rather than collapsing the doses into one treatment category. The endpoint also has a clear operational definition involving on-time, off-time symptoms, sleep, and dyskinesia-related difficulty with voluntary movement.

The posted summary illustrates why point estimates should not be interpreted without precision. The mean differences from placebo are close to zero in the reported units, while the confidence intervals extend across zero and include values in both directions. The group standard deviations are substantial relative to those estimates. Taken together, these features show that the recalculated comparisons are not precise enough to isolate a clear average difference.

The record also provides a useful distinction between trial design and retrospective planning illustrations. The planning figures are based on observed effects under stated assumptions, whereas the trial’s own design assumptions are not reported in the registry record. These illustrations should not be mistaken for the original sample-size rationale or as evidence of observed power.

Finally, the record highlights the limits of registry reporting for statistical interpretation. It identifies the primary population and outcomes, but does not report the analysis plan, multiplicity procedure, or missing-data methods. Reading the results with those omissions in mind helps keep descriptive summaries separate from confirmatory inference. That distinction matters when several doses and outcomes are considered together.

18. 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’s primary outcome summaries do not include a reported sponsor analysis. The comparisons and confidence intervals discussed are unadjusted recalculations from posted group means, standard deviations, and sample sizes. The original statistical model, any baseline adjustment, and any handling of repeated observations are not reported in the registry record.

The modified intent-to-treat population requires treatment exposure and at least one follow-up efficacy assessment. The record does not report participant flow by arm for the primary analysis beyond the posted sample sizes, reasons for missing follow-up, diary completion, or methods used for missing outcome data. These details matter because the available summaries may not represent every randomized participant in the same way.

The endpoint relies on participant diary entries. The registry defines the recorded concept but does not report diary adherence, validation information, or how incomplete or inconsistent entries were treated. The primary follow-up is at Week 12; longer-term results for this endpoint are not reported in the registry record.

Several doses and outcomes are listed, but the registry does not report the original multiplicity plan or outcome hierarchy. The unadjusted comparisons therefore do not account for all the tests that might have been considered. No equivalence margin or clinically important difference is reported, so neither a claim of equivalence nor a threshold-based assessment of clinical importance can be made from the record.

The serious adverse event summaries give participant counts but do not list serious-event terms, and death counts are not reported in the registry record. Event timing and attribution are also not described in the posted information. These limitations constrain interpretation of safety alongside the efficacy summaries.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Sarizotan in Participants With Parkinson's Disease Suffering From Treatment Associated Dyskinesia — NCT00105521.
• Registry record last updated 2018-04-02; status last verified 2017-09.
• Results first posted 2018-04-02.
• 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.

22. Record Summary

NCT00105521 is a completed randomized, double-blind, parallel-group Phase III study of sarizotan in participants with Parkinson’s disease and treatment-associated dyskinesia. The record lists 398 enrolled participants and four groups: placebo and sarizotan at 2 mg/day, 4 mg/day, or 10 mg/day, administered up to Week 12.

The primary endpoint was change from baseline in diary-based on-time without dyskinesia at Week 12. Posted group means ranged from 1.6 to 1.9 hours/day. The unadjusted recalculated mean differences versus placebo were 0.3, 0.1, and 0.2 hours/day, with confidence intervals that include zero. The registry does not report sponsor analyses, the original statistical plan, multiplicity handling, or missing-data methods.

Secondary outcomes and serious adverse event counts are also recorded. These summaries offer descriptive context but do not resolve the uncertainty in the primary comparisons or replace detailed analysis and safety reporting.