Quantification of the Antidyskinetic Effect of Amantadine and Topiramate in Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Quantification of the Antidyskinetic Effect of Amantadine and Topiramate in Parkinson's Disease (NCT00794313), a randomized na study. The primary outcome is Forceplate AUC.

2. Clinical Question

The clinical question is therefore about measurement as well as treatment: how the forceplate outcome varies across the listed treatment conditions in a triple crossover study. The registry’s brief description says that objective measurement of these movements was the study’s purpose. It does not report a formal hypothesis, a defined treatment contrast, or a prespecified claim about the size of a clinically meaningful change. The posted endpoint summaries describe the three arms, but they do not establish whether observed differences are attributable to treatment, chance variation, or other factors. Because the record lists enrollment of 3 and provides no posted analyses, the available information supports a descriptive reading only.

3. Trial Design

The record describes a randomized, double-masked crossover study with a triple cross-over design. Its listed arms are amantadine, amantadine plus topiramate, and sugar pill. Enrollment was 3. The record lists amantadine 300 mg and topiramate as drug interventions, alongside a sugar pill. It does not give further details about the allocation sequence, the masking procedures, treatment-period length, or whether a washout period was used.

The study began in 2009-09, had a primary completion date of 2010-06, and is marked terminated. The phase is listed as NA. Oregon Health and Science University is the sponsor. These registry entries describe the study’s status and organization; they do not explain why the study was terminated. The reason for termination is not reported in the registry record.

In a crossover design, participants receive more than one study condition over time, so an individual can contribute observations under multiple conditions. This design can support within-participant comparisons, but interpretation depends on details such as treatment order, period effects, carryover, and which participants completed each period. Those details are not reported in the registry record. Although all three arm summaries list 3 participants, the record does not explain whether those counts represent the same participants measured repeatedly, nor does it give a participant flow description.

The registry reports continuous outcome summaries by arm but no posted analyses. The record does not report a sample-size justification, a statistical analysis plan, an interim analysis plan, or the reason for stopping. The design labels alone cannot establish how the planned comparisons were to be analyzed or whether all planned observations were collected.

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: triple cross-over study design.

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 Forceplate AUC, measured over Every 1/2 hour for 8 hour levodopa cycle.

The primary endpoint is titled Forceplate AUC, with units of (meters/second)*hours. The registry describes it as the area under the curve for root mean squared velocity in the anterior-posterior direction, measured by a forceplate. Measurements were scheduled every 1/2 hour for an 8 hour levodopa cycle. The endpoint is reported as a mean with standard deviation.

In general, an area-under-the-curve measure combines repeated measurements across a defined observation period into a single summary. Here, the described curve is based on forceplate velocity measurements during the levodopa cycle. A forceplate offers an instrument-based way to quantify movement, aligning with the study description’s aim to use an objective measure of dyskinesia. The registry does not report validation information for this particular endpoint, nor does it state what magnitude of change would be important to participants or clinicians.

The posted arm means are 10.4 for amantadine, 9.4 for amantadine plus topiramate, and 19.1 for sugar pill. Their corresponding standard deviations are 5.6, 3.5, and 18.8. These summaries describe the observed endpoint values; they do not by themselves quantify the uncertainty in treatment contrasts. The registry does not provide confidence intervals for the means or comparisons.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary outcome as a mean and standard deviation for each arm. A continuous measure can take a range of numeric values; in this study, it is the forceplate area-under-the-curve measure. The mean describes the center of the observed values, while the standard deviation describes their spread. Neither statistic alone is a treatment comparison, and neither gives the uncertainty around a contrast between arms.

What does a crossover design change?

In general, a crossover design measures participants under more than one condition. This can make within-participant comparisons informative because each person’s measurements across conditions can be related. Such analyses rely on the pattern of repeated observations, not just separate arm means and standard deviations. Period effects, carryover from an earlier condition, treatment order, and missing periods can matter. The registry identifies the study as randomized, double-masked, and crossover, and describes a triple cross-over design. It does not report the sequence, period structure, washout, completion pattern, or the statistical handling of these design features.

Why are no treatment comparisons interpreted?

The registry lists 0 analyses. It also indicates that values are missing or not estimable for a two-arm comparison of the continuous endpoint. Consequently, there is no posted treatment contrast, p-value, or confidence interval to interpret. A p-value, in general, summarizes how compatible observed data are with a specified statistical model and null hypothesis; it does not measure the size or importance of an effect. A confidence interval, in general, gives a range of estimates compatible with the data and model at a stated confidence level. Neither is reported for the primary endpoint comparison.

Comparing the three means informally would omit the uncertainty and, for a crossover study, the relationships between each participant’s measurements across treatment conditions. The arm summaries cannot reconstruct those relationships. The sponsor’s own analysis takes precedence when a discrepancy is present; the registry marks no discrepancy, but that does not supply an analysis that is absent from the posted results.

How should the spread be read?

Standard deviation is a measure of variation among observations, not a measure of precision in the estimated treatment effect. In general, a confidence interval for a contrast would require an appropriate analysis and information about the data structure. For repeated measurements, that analysis would need to account for the within-participant pattern. A standard deviation reported separately for each arm does not reveal the covariance or correlation between measurements from the same participant. The registry does not report those details or uncertainty intervals.

Over-dispersion is a general concern when the variability in data is larger than a model assumes. In a continuous endpoint, unusually large spread can make a simple model’s uncertainty estimates unreliable if the model does not accommodate that variation. The sugar-pill arm has a reported standard deviation of 18.8, compared with a mean of 19.1. This descriptive spread merits caution, but without individual observations and a posted model it is not possible to determine its source or its impact on a treatment comparison.

What do the planning illustrations mean?

The record describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The planning effect is defined as a stated fraction of the observed effect. These are illustrations, not the trial’s own design justification, and they are not observed power. The record does not report a sample-size justification from the trial protocol. A planned sample size is an assumption-based calculation about a future design; it is not evidence that the trial had adequate precision or that an effect was detected. The record does not report calculated planning values in the registry record for this analysis.

These methods points distinguish descriptive summaries from an analyzed treatment effect. The posted means and standard deviations can characterize the endpoint values in the arms, but without a reported analysis that accounts for the crossover design and gives uncertainty, they cannot establish the magnitude or precision of a treatment contrast. The record does not report the statistical plan, model, covariates, analysis populations, or handling of missing observations.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Amantadine", "Amantadine Plus Topiramate", "Sugar Pill")
n   <- c(3, 3, 3)
m   <- c(10.4, 9.4, 19.1)
sp  <- c(5.6, 3.5, 18.8)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Amantadine  3  10.400  5.600  -3.511  24.311
CARM  Amantadine Plus Topiramate  3  9.400  3.500  0.706  18.094
CARM  Sugar Pill  3  19.100  18.800  -27.602  65.802

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and identifies one secondary outcome: Modified Abnormal Involuntary Movement Scale Area Under the Curve. The primary outcome is Forceplate AUC. The record lists 0 analyses, so it does not provide posted results for a statistical comparison of either endpoint. It does not report a multiplicity strategy for handling inference across outcomes or treatment contrasts. In general, multiplicity refers to the increased chance of misleading findings when several hypotheses are tested; the registry information does not establish how this issue was addressed.

The registry does not report a statistical analysis plan, a prespecified hierarchy among outcomes, or a definition of which treatment comparisons were intended. It also does not report an analysis population, such as an intention-to-treat or per-protocol population. The arm summaries each list 3 participants, but the record does not describe participant flow, the number completing each period, or whether all participants contributed data to every arm summary.

Missing-data methods and reasons for missing observations are not reported in the registry record. Nor are details given about exclusions, protocol deviations, or how incomplete crossover sequences were handled. These omissions matter because incomplete repeated measurements can affect which participants contribute to each comparison and how precisely a contrast can be estimated. The available record supports a description of the posted arm summaries, but not a conclusion about the completeness or analysis population behind them.

12. 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 non-serious adverse event terms

The serious adverse event figures list 3 participants at risk in each arm and 0 affected by serious adverse events in each arm: amantadine, amantadine plus topiramate, and sugar pill. These are the posted counts, not evidence that serious harms are impossible or that the treatments have equivalent safety. With enrollment of 3 and no posted analysis, the figures offer limited information about the frequency of uncommon events.

The record also lists other, non-serious adverse events: 0 of 3 for amantadine, 2 of 3 for amantadine plus topiramate, and 3 of 3 for sugar pill. The registry does not provide event terms in the posted safety details, so these counts do not indicate what kinds of events occurred or their timing. Death counts are not reported in the registry record.

In general, adverse-event counts describe what was recorded among participants at risk during the study; they do not by themselves establish whether an event was caused by a treatment. The registry does not report an analysis comparing safety between arms, exposure duration, or details needed to interpret the event counts in the context of the crossover periods.

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

The posted primary outcome summaries show Forceplate AUC means of 10.4 for amantadine, 9.4 for amantadine plus topiramate, and 19.1 for sugar pill. The respective standard deviations are 5.6, 3.5, and 18.8. The values are descriptive summaries from a study with enrollment of 3 and a triple crossover design. They indicate how the reported endpoint values were distributed in the arm summaries; they do not provide a reliable estimate of a treatment effect by themselves.

The record does not post a treatment comparison, confidence interval, p-value, or analysis of the primary endpoint. It also does not report participant-level paired measurements, so readers cannot assess whether individual participants had a similar pattern across conditions. In a crossover design, that within-person pattern is important to interpreting comparisons. The available arm summaries do not show the contribution of treatment order, period effects, or possible carryover.

The study’s brief description frames the objective as measuring movement reduction using an objective measure. The posted forceplate outcome addresses that measurement aim, but the registry information does not establish that the endpoint is validated for this use or define a clinically meaningful difference. Nor does it establish that any observed difference in the arm means is attributable to treatment.

The study is marked terminated, but the reason for termination is not reported in the registry record. The record does not report the protocol’s sample-size justification, interim analyses, or statistical plan. Thus, the reported values should be read as limited descriptive results rather than a definitive treatment comparison. They neither demonstrate a treatment effect nor establish an absence of one. Further interpretation would require information not reported in the registry record, including the planned analysis, the crossover sequence and completion pattern, and uncertainty estimates for relevant contrasts.

14. Why This Trial Matters Statistically

This trial illustrates how an objective measurement strategy and a treatment-effect question are related but distinct. The registry describes a forceplate endpoint intended to quantify movement during a levodopa cycle. Reporting that endpoint as an area under the curve gives a numeric summary across repeated measurements. But a measurable outcome is not, by itself, evidence of a treatment effect. A study also needs an analysis that compares conditions in a way suited to its design and reports uncertainty around the result.

The crossover structure makes that distinction especially clear. When participants are observed under multiple conditions, the individual pattern across periods can carry important information. Arm-level means and standard deviations do not preserve the pairing between observations. Without a posted comparison, readers cannot tell how the repeated measurements were used or how the analysis addressed period and carryover considerations.

The record also demonstrates the limits of interpreting small descriptive datasets. Enrollment was 3, and the study is marked terminated. The reported arm means are accompanied by substantial variation, particularly for the sugar-pill arm, but no confidence intervals or inferential analyses are posted. This means that readers have no direct estimate of the precision of treatment contrasts from the registry results.

Finally, the record separates a study’s stated objective from what its posted results can support. The objective was to measure dyskinesia with an objective approach. The registry reports endpoint summaries and adverse-event counts, but not the planned analysis, the reason for termination, or the inferential findings. Statistically, the appropriate conclusion is bounded by that reporting: the data provide descriptive values, while the comparative treatment question remains unresolved in the posted results.

15. 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 details needed to assess this particular study are not reported in the registry record. The record does not state why the study was terminated, how many participants completed each treatment period, or whether each participant contributed to every arm summary. Although each arm lists 3 participants, the relationship between those arm counts and the repeated observations implied by the triple crossover design is not explained.

The registry does not report treatment order, period length, washout procedures, or methods for assessing period effects or carryover. These are relevant to interpreting a crossover study because measurements under one condition may be connected to measurements under another condition for the same participant. Without participant-level data or a stated model, those dependencies cannot be assessed from the means and standard deviations alone.

The record does not provide confidence intervals, p-values, adjusted estimates, or a statistical analysis plan for the primary endpoint. It also does not report the sample-size justification, the reasons for choosing the endpoint, or a threshold for a clinically meaningful difference. The summary description says measurements were scheduled every 1/2 hour for an 8 hour levodopa cycle, but completeness of those repeated measurements is not reported.

Safety interpretation is also constrained: death counts are not reported in the registry record, and the posted other-adverse-event counts are not accompanied by event descriptions in the record details available for this analysis. The registry does not describe exposure duration or a safety comparison. Together, these gaps limit conclusions about the endpoint, treatment contrasts, and safety. The reported values remain descriptive rather than a complete account of the study’s comparative findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Quantification of the Antidyskinetic Effect of Amantadine and Topiramate in Parkinson's Disease — NCT00794313.
• Registry record last updated 2018-02-01; status last verified 2018-01.
• Results first posted 2017-05-11.
• 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.

19. Record Summary

The registry describes NCT00794313, Quantification of the Antidyskinetic Effect of Amantadine and Topiramate in Parkinson's Disease, as a randomized, double-masked crossover study sponsored by Oregon Health and Science University. It lists enrollment of 3, a start date of 2009-09, primary completion in 2010-06, and status as terminated. The arms are amantadine, amantadine plus topiramate, and sugar pill.

The primary outcome is Forceplate AUC, a continuous measure reported as mean and standard deviation. The posted means are 10.4, 9.4, and 19.1, respectively, with standard deviations of 5.6, 3.5, and 18.8. The registry lists 0 analyses and says values are missing or not estimable for a two-arm comparison of the continuous endpoint. It also lists 2 outcome measures, including a secondary Modified Abnormal Involuntary Movement Scale Area Under the Curve outcome.

Serious adverse event counts are 0 affected among 3 at risk in each arm. Other adverse-event counts are 0 of 3, 2 of 3, and 3 of 3, respectively. The reason for termination and key analysis details are not reported in the registry record.