Efficacy and Safety of Amantadine Hydrochloride (HCl) ER Tablets to Treat Parkinson's Disease Patients With LID.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Amantadine Hydrochloride (HCl) ER Tablets to Treat Parkinson's Disease Patients With LID. (NCT02153645), a randomized phase 3 study. The primary outcome is Unified Dyskinesia Rating Scale.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, parallel-group, placebo-controlled study described as multicenter and double-blind. The registry lists quadruple masking. It does not specify which people or study roles were masked, the method used to create the randomization sequence, or whether allocation was stratified. The allocation ratio is not reported in the registry record.

The study compared two daily dose levels of amantadine hydrochloride extended-release tablets, 240mg and 320mg, with matching placebo tablets. For the active-dose groups, the descriptions specify a two-week titration phase followed by 12 weeks at the target daily dose. Placebo was taken daily for 16 weeks. The overall study duration is described as 16 weeks, and the primary outcome timeframe is baseline to Day 98.

The registry reports 87 participants enrolled, against 162 planned. It states that the study was terminated early because enrollment was slow. This enrollment shortfall is important context when considering how much information the trial could contribute, but the record does not give the original statistical power calculation, the planned allocation by arm, or an explanation of how early termination affected the analysis.

The primary outcome was the change in UDysRS score from baseline to Day 98. A secondary outcome was Mobility State Self-Assessment using subject diary cards. The registry lists two outcome measures and two analyses, but further detail on the analyses is not reported in the registry record. The record does not identify analysis populations, describe handling of missing observations, or provide the statistical model used for the primary comparison.

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

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 Unified Dyskinesia Rating Scale, measured over From baseline to Day 98.

The primary endpoint was change from baseline to Day 98 in the sum of the 26 questions of the Unified Dyskinesia Rating Scale. The UDysRS is described as a validated tool for assessing dyskinesia, or involuntary movements, in people with Parkinson’s disease. Its questions cover time spent with and without dyskinesia, difficulties in everyday activities, impairment across body parts, and disability in activities such as communication, drinking from a cup, dressing, and walking.

Each question is rated on a five-point scale from 0 to 4. The total score ranges from 0, which is better, to 130, which is worse. A change score therefore expresses how the total rating differs between baseline and Day 98; interpreting that change requires knowing the direction used in the analysis as well as the numerical estimate. The registry describes the endpoint as a mean of a continuous measure with standard deviation as its dispersion, but numerical group summaries are not reported in the registry record.

A scale covering several aspects of dyskinesia can represent more than a single symptom or activity. However, a total score alone does not show which specific experiences account for a change. The registry record does not report the primary endpoint’s numerical results, so it is not possible to describe the size or precision of any group difference from the primary outcome information recorded.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a mean of a continuous measure, with standard deviation as the dispersion measure. A continuous score can take a range of numerical values rather than belonging only to a set of categories. The UDysRS total is formed from multiple ratings, and the endpoint is its change from baseline to Day 98. The registry does not provide the observed means, standard deviations, or group comparisons.

What does a mean and standard deviation describe?

In general, a mean describes the center of a set of numerical observations. A standard deviation describes how spread out individual observations are around that center. These answer different questions: two groups can have similar means but different variability, or different means with substantial overlap in individual scores. A mean difference alone does not show the range of individual experiences. In this study, the registry identifies mean and standard deviation as the summary approach, but does not report their numerical values for the primary outcome.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the analysis. Its width conveys precision: a wider interval indicates greater uncertainty about the estimated effect than a narrower interval. A confidence interval is not a guarantee that the true effect lies within the particular interval. The registry record does not report confidence intervals for the primary endpoint, so the precision of the planned treatment comparisons cannot be assessed from those results.

How should a p-value be understood?

In general, a p-value describes how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. A small p-value, by itself, would not establish that a difference matters in practice; a larger p-value would not establish that groups are equivalent. Primary endpoint p-values are not reported in the registry record.

What does the planning illustration mean?

The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The planned effect to detect is described as a stated fraction of the observed effect. These are assumptions for planning illustrations, not a report of the trial’s own design justification. The registry record does not report the trial’s original sample-size justification or the numerical results of those illustrations. Any sample-size illustration is a planning quantity, not observed power and not evidence that a trial did or did not detect an effect.

In general, sample-size planning depends on the effect size selected for planning, outcome variability, the chosen significance level, the desired power, and the design. If the actual enrolled group is smaller than planned, estimates may be less precise than anticipated, but the degree of change cannot be calculated from enrollment alone. The registry does not report all inputs needed to reconstruct the original design calculation. The planned enrollment was 162 and reported enrollment was 87; the reason given for termination was slow enrollment.

Why does multiplicity matter?

In general, testing multiple outcomes, time points, dose comparisons, or subgroups can increase the chance of at least one apparently notable result arising by chance if no adjustment or prespecified hierarchy is used. A statistical plan may address this through a testing sequence or other adjustment. The record identifies a primary endpoint, a secondary diary-card outcome, two outcome measures, and two analyses, but does not report a multiplicity strategy or a testing hierarchy. It is therefore not possible to determine from the record how multiple statistical questions were handled.

Why can over-dispersion matter?

In general, over-dispersion means that the observed variability is greater than a statistical model expects. It is especially relevant to some count or binary-outcome models because underestimated variability can make uncertainty intervals too narrow and tests too optimistic. The primary endpoint is a continuous scale score, and the registry specifies standard deviation as its dispersion summary. It does not report a model or an assessment of over-dispersion; no claim about over-dispersion in this trial can be made from the record.

Other important methodological details are not reported in the registry record, including the exact primary analysis model, covariate adjustment, the analysis population, missing-data methods, and sensitivity analyses. General statistical principles can explain why these details matter, but they cannot substitute for the trial’s actual analysis plan or results.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies change in UDysRS score from baseline to Day 98 as the primary endpoint and Mobility State Self-Assessment using subject diary cards as a secondary outcome. It lists two outcome measures and two analyses. These registry entries do not establish which analyses correspond to which comparisons, whether there were additional time points or dose comparisons, or whether the analyses followed a prespecified hierarchy.

In general, multiplicity arises when several statistical questions are examined, such as comparisons across multiple arms or endpoints. Without a prespecified approach, the chance of at least one chance finding can increase. A testing hierarchy or adjustment can help control that issue, but the registry record does not report whether either was used. The record also does not report an interim-analysis plan or whether any interim analyses took place. No interim process should be inferred from early termination alone.

Missing-data handling is also not reported in the registry record. It does not state how many participants had a Day 98 UDysRS measurement, how incomplete diaries were handled, or what assumptions or sensitivity analyses were used for missing observations. The analysis population is not reported: the record does not say whether the primary analysis used all randomized participants, only participants with outcome measurements, or another defined group.

These omissions limit interpretation because missingness and analysis choices can affect both the estimate and its uncertainty. The enrollment total alone does not establish how many participants contributed to each outcome analysis. The record’s early-termination explanation is slow enrollment; it does not describe whether incomplete follow-up or any statistical review contributed to the decision.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: impulse-control disorder (3.6%), arrhythmia supraventricular (3.6%), syncope (3.4%), traumatic haemothroax (3.3%), megacolon multi-organ failure (3.3%).

The serious adverse-event figures are reported by treatment group. In the 240mg amantadine group, 3 of 30 participants were affected; in the 320mg group, 1 of 29 was affected; and in the placebo group, 2 of 28 were affected. The separate other-adverse-event counts were 20 of 30, 24 of 29, and 15 of 28, respectively. Recorded deaths were 1 in the 240mg group, 0 in the 320mg group, and 0 in the placebo group.

These are counts of participants recorded in each category, not estimates of the cause of an event. The registry does not report whether any death or adverse event was judged related to treatment, nor does it provide event timing or individual clinical details. The record lists serious-event terms with percentages, but those terms do not explain causality or provide a basis for comparing overall risk without further context. The counts should be read as descriptive safety information, not as proof that an intervention caused or prevented an event.

The group denominators are the participants at risk recorded for each adverse-event category. They need not be assumed to describe the number with complete primary outcome data. The record does not report statistical comparisons for these safety counts or uncertainty intervals.

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

The registry record describes a randomized comparison of 240mg and 320mg amantadine hydrochloride extended-release tablets with placebo in people with Parkinson’s disease and levodopa-induced dyskinesia. It identifies change in UDysRS score from baseline to Day 98 as the primary endpoint and gives the score’s direction and range. It also reports the study’s early termination because enrollment was slow, with 87 participants enrolled against 162 planned.

What the record does not report is the numerical primary endpoint result. There are no reported group means or changes, standard deviations, treatment-effect estimates, confidence intervals, or p-values for that endpoint in the information recorded. Consequently, the magnitude and precision of the primary comparison cannot be described. The absence of those results in the registry record is not evidence that the groups were the same, nor is it evidence of a difference.

The safety counts provide descriptive information about participants with serious and other adverse events and about deaths. They do not determine whether an event was related to an intervention. A causal interpretation would require more information about event definitions, timing, clinical review, and the analysis, which is not reported in the registry record.

In general, a randomized, masked, placebo-controlled design can help limit certain sources of bias when implemented and analyzed appropriately. That general design principle does not resolve questions about the actual results, missing outcome data, analysis populations, or statistical procedures in this study. Those details are not reported in the registry record.

The most defensible reading is therefore bounded: the record describes the intended comparison, the primary measure, early termination, and adverse-event counts. It does not provide the primary efficacy results needed to quantify comparative change or its uncertainty. No medical decision or conclusion that a treatment works or does not work should be drawn from these registry entries alone.

13. Why This Trial Matters Statistically

This trial is statistically notable because enrollment ended well below the planned total. The registry reports 87 enrolled against 162 planned and attributes early termination to slow enrollment. When a study enrolls fewer participants than planned, the resulting estimates may be less precise than the design intended. The amount of any loss of precision cannot be determined from the enrollment figures alone, and the record does not report the original sample-size justification or primary outcome estimates.

The endpoint also illustrates the distinction between a measurement definition and a statistical result. The registry explains what the UDysRS assesses, its score range, and the direction of better and worse outcomes. Those details support interpretation of a reported change, but do not reveal the observed change. Without numerical group results and uncertainty measures, the primary comparison remains unquantified.

There is a further interpretive distinction between a planned trial and its reported analysis. The study was randomized, masked, and placebo-controlled as described, but the registry does not report the primary analysis model, analysis populations, multiplicity strategy, or missing-data approach. Those choices can affect how an estimate should be read, especially when a trial stops early and outcome completeness is unknown.

The safety figures add descriptive information, but they do not replace the missing primary endpoint results or establish event causation. Taken together, the record is a useful illustration of why design, enrollment, endpoint definition, analysis transparency, and results all matter. A well-defined question alone is not enough to assess the strength or precision of an answer.

14. 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 central limitation for statistical interpretation is that numerical primary endpoint results are not reported in the registry record. The endpoint is defined, but group changes, dispersion estimates, between-group effects, confidence intervals, and p-values are absent. The primary comparison’s size and precision therefore cannot be assessed.

Enrollment was 87 of 162 planned, and the study was terminated early because enrollment was slow. The record does not report the original sample-size justification, whether the planned analysis changed after termination, or the extent of primary outcome follow-up. It also does not report how many participants contributed data to each endpoint.

The registry does not report the randomization method, allocation ratio, analysis populations, primary statistical model, covariate adjustments, missing-data methods, sensitivity analyses, or multiplicity procedures. It does not describe an interim-analysis plan or state whether interim analyses occurred. These omissions prevent a detailed assessment of how the intended comparisons were implemented and how robust they might be to analysis choices.

The outcome information is limited to the primary measure’s description and the named diary-card secondary outcome. Numerical secondary outcome results are not reported in the registry record. The safety figures are counts by group, without reported inferential comparisons, event timing, or treatment-causality assessments. The listed serious-event terms and percentages do not supply those missing details.

Finally, the record describes a multicenter study and lists quadruple masking, but does not explain the masked roles or give further site or participant characteristics. These limits do not show that a particular bias occurred; they specify what cannot be evaluated using the registry information recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of Amantadine Hydrochloride (HCl) ER Tablets to Treat Parkinson's Disease Patients With LID. — NCT02153645.
• Registry record last updated 2022-02-16; status last verified 2022-02.
• Results first posted 2019-04-02.
• 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.

18. Record Summary

This Phase 3 study was a randomized, parallel-group, placebo-controlled comparison of 240mg and 320mg amantadine hydrochloride extended-release tablets with matching placebo in people with Parkinson’s disease and levodopa-induced dyskinesia. It was described as multicenter and double-blind, with quadruple masking listed in the registry. Active-dose descriptions specify a two-week titration phase followed by 12 weeks at the target dose; placebo was taken daily for 16 weeks.

The primary endpoint was change in UDysRS score from baseline to Day 98. Enrollment was 87 against 162 planned, and the study was terminated early because enrollment was slow. The registry record does not report numeric primary outcome results or the main statistical analysis details. It reports serious and other adverse-event counts and deaths by treatment group, but does not report event causality. These limitations mean the primary comparative effect and its precision cannot be assessed from the recorded results.