This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Long-term Safety of Rivastigmine Capsule and Patch in Patients With Mild to Moderately-severe Dementia Associated With Parkinson's Disease (PDD) (NCT00623103), a randomized phase 3 study. The primary outcome is Percentage of Participants With Adverse Events (AEs) Due, or Potentially Due, to Worsening of Parkinson Disease (PD) Motor Symptoms (Tremor, Muscle Rigidity, Bradykinesia, Fall).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00623103 |
| Phase | Phase 3 |
| Condition | Parkinson's Disease Dementia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 583 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis |
| Results posted | Yes |
2. Clinical Question
Population
People with mild to moderately severe dementia associated with Parkinson’s disease (PDD). The primary outcome population is described as participants who received at least one dose of study drug and had at least one post-baseline safety measurement; participants with an observation at 76 weeks were included in that analysis.
Intervention
Rivastigmine capsules or a rivastigmine transdermal patch. The capsule regimen started at 3 mg/day, with increases in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day or the highest tolerated dose. The patch started at 5 cm^2, delivering 4.6 mg over 24 hours, and was increased after 4 weeks to 10 cm^2 daily, delivering 9.5 mg over 24 hours.
Comparator
The two rivastigmine formulations were compared with each other in a randomized, parallel-group study. The registry does not describe a placebo or untreated comparator. The study was unmasked, so treatment assignment was not concealed from participants and investigators.
Primary question
Over 76 weeks, what percentage of participants in each treatment group had an adverse event considered due, or potentially due, to worsening of Parkinson’s disease motor symptoms, or discontinued because of one of the predefined events: tremor, muscle rigidity, bradykinesia, or fall? The registry record does not report the primary outcome results by treatment group.
3. Trial Design
This was a Phase 3, randomized, parallel-group, open-label study of rivastigmine capsule and transdermal patch treatment in people with dementia associated with Parkinson’s disease. The registry lists enrollment of 583. It describes the study as prospective, multicenter, and lasting 76 weeks. The study status is completed.
Participants were assigned to one of the two rivastigmine formulations. The record does not describe a placebo group or a group receiving no study treatment. Because masking was listed as none, the study was unmasked: participants and study personnel could know which formulation was being used. This matters when interpreting outcomes that involve clinical judgment or reporting, including whether an event was considered related to worsening motor symptoms.
The capsule began at a total dose of 3 mg/day, given as 1.5 mg twice daily orally. The dose was titrated upward in 3 mg/day increments every 4 weeks to 12 mg/day, or the highest tolerated dose. The 12 mg/day dose or highest tolerated dose was maintained until week 76. The patch was applied once a day in the morning and worn for 24 hours. It began at 5 cm^2, delivering 4.6 mg over 24 hours, for 4 weeks, then was titrated to 10 cm^2 daily, delivering 9.5 mg over 24 hours. The registry record does not give the remainder of the patch arm’s dose-maintenance description.
The primary outcome focuses on adverse events due, or potentially due, to worsening of Parkinson’s disease motor symptoms. Secondary outcomes include changes in motor, cognitive, neuropsychiatric, daily-living, and disease-stage measures at scheduled follow-up points. The registry record does not report the randomization procedure, allocation concealment, the rationale for the enrollment target, or additional operational details beyond those stated.
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
| Stage | Rivastigmine Capsule | Rivastigmine Patch |
|---|---|---|
| STARTED | 295 | 288 |
| Safety Set: Received Study Drug | 294 | 288 |
| COMPLETED | 184 | 175 |
| NOT COMPLETED | 111 | 113 |
Reasons for not completing this period:
| Reason | Rivastigmine Capsule | Rivastigmine Patch |
|---|---|---|
| Adverse Event | 70 | 60 |
| Unsatisfactory therapeutic effect | 4 | 12 |
| Withdrawal by Subject | 18 | 24 |
| Lost to Follow-up | 4 | 1 |
| Administrative problems | 2 | 4 |
| Death | 11 | 11 |
| Protocol deviation | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety Population consisted of all participants who received at least 1 dose of study drug and had 1 post-baseline safety measurement. Participants with observation at 76 weeks were included in this analysis.
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.
| Characteristic | Unit | Rivastigmine Capsule | Rivastigmine Patch | Total |
|---|---|---|---|---|
| Participants analysed | 295 | 288 | 583 | |
| Age Continuous | years | 72.35 (SD 6.295) | 72.26 (SD 6.352) | 72.31 (SD 6.318) |
| Sex: Female, Male: Female | Participants | 88 | 97 | 185 |
| Sex: Female, Male: Male | Participants | 207 | 191 | 398 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Adverse Events (AEs) Due, or Potentially Due, to Worsening of Parkinson Disease (PD) Motor Symptoms (Tremor, Muscle Rigidity, Bradykinesia, Fall), measured over 76 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with an adverse event judged due, or potentially due, to worsening of Parkinson’s disease motor symptoms during the 76-week timeframe. The endpoint includes any of four predefined events: tremor, muscle rigidity, bradykinesia, and fall. It also includes participants who discontinued because of any of those events. The registry says the outcome was to be summarized by the number and percentage in each treatment group, with associated 95% confidence intervals.
This endpoint was intended to capture a safety concern specific to this population and treatment context: whether worsening motor symptoms were observed or suspected during long-term use. Combining the listed events into an endpoint can provide a focused summary of that concern, rather than treating each event as the sole outcome. Including discontinuation due to a predefined event also recognizes that an event may affect whether treatment continues.
The endpoint is not a direct measure of motor function over time. Separate secondary outcomes address change in the Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination and other measures. Nor does the endpoint, by itself, establish that treatment caused an event: the registry’s wording includes events considered potentially due to worsening motor symptoms, and this study was open-label.
Although the endpoint definition and intended summary are recorded, the group-specific numbers, percentages, and confidence intervals for this outcome are not reported in the registry record. Therefore, the primary outcome’s observed rates and the precision of any comparison cannot be described from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry specifies a clinically focused safety outcome, but does not report its results. It is therefore not possible to state the percentage of participants in either formulation group who experienced the primary endpoint, to compare those percentages, or to describe the precision of a group difference. The record’s description of how the outcome was to be summarized is not a substitute for the actual event counts and rates.
The posted serious adverse event figures list 87 participants with serious adverse events among 294 at risk in the Exelon Capsule group and 83 among 288 at risk in the Exelon Patch group. The record also lists 239 among 294 and 215 among 288 for other adverse events, respectively. These are counts and denominators as recorded; no new rates or between-group differences are calculated. They should not be mistaken for the primary endpoint, which is limited to adverse events related or potentially related to worsening of the specified motor symptoms, or discontinuations due to those events.
The listed serious adverse event terms include Fall and Pneumonia, each at 3.1%; Confusional state at 2.1%; Femur fracture at 2.0%; Syncope at 1.7%; and Urinary tract infection at 1.4%. These term-specific percentages do not give a complete account of all serious events, and the registry record does not state the denominator or event-counting convention for these percentages. A participant may have more than one event, so term percentages should not be added or treated as mutually exclusive categories.
Other registry outcomes include repeated assessments of motor function and measures of cognition, neuropsychiatric symptoms, daily activities, and disease stage. Their presence in the outcome list does not establish what the findings were. Outcome results beyond the adverse-event counts and listed serious-event terms are not reported in the registry record.
The registry’s open-label design is relevant to interpretation, particularly for outcomes that depend on event attribution or clinical assessment. Randomization supports a planned comparison of the formulations, but does not resolve uncertainty created by missing outcome results, incomplete reporting, or possible differences in how treatment-related events were assessed. No conclusion about comparative safety on the primary endpoint can be drawn from the information recorded.
9. Statistical Methods Explained
The registry describes the primary outcome as a percentage and says that the number and percentage of participants with the endpoint, along with 95% confidence intervals, were to be presented for each treatment group. The endpoint combines adverse events due or potentially due to worsening motor symptoms with discontinuations caused by any of the predefined events. However, the registry record does not report the outcome counts, percentages, or confidence intervals. Consequently, no estimate of the primary endpoint’s treatment-group rates or their uncertainty can be interpreted from this record.
What does a percentage measure?
In general, a percentage for a binary outcome expresses how often an event was recorded within a defined group. It is useful for describing the observed frequency, but its interpretation depends on the outcome definition, the population included, and the time period. For this trial, the defined endpoint concerns specified motor-symptom-related adverse events or discontinuations over 76 weeks. Without the actual numerator and denominator for that endpoint in each group, the percentages cannot be reconstructed or checked.
The safety population definition is specific: participants had to receive at least one dose and have at least one post-baseline safety measurement. The primary outcome description further says that participants with an observation at 76 weeks were included in the analysis. These details matter because the analyzed population and available follow-up can affect the denominator. The registry does not provide a fuller account of how participants without a 76-week observation were handled for this endpoint.
What does a confidence interval add?
In general, a confidence interval communicates the statistical uncertainty around an estimate. For a group percentage, it indicates a range of values compatible with the observed data under the method used. A narrower interval usually indicates greater precision, while a wider interval indicates more uncertainty. The registry says 95% confidence intervals were presented for the primary endpoint, but those intervals are not reported in the registry record. Their width and the precision of the group estimates therefore cannot be assessed.
A confidence interval is not a guarantee that the true value lies within its particular limits, nor does overlap or non-overlap alone replace a prespecified comparison method. The record does not report a treatment-effect estimate or an inferential test for the primary outcome. The number of analyses is listed as zero, and the registry does not provide outcome analyses from which such a comparison could be described.
Why does open-label assessment matter?
In general, open-label status means treatment assignment is known rather than masked. Knowledge of treatment can influence symptom reporting, clinical observation, or attribution of an event to a treatment or to disease worsening. Randomization can help balance participant characteristics across groups at assignment, but it does not eliminate the possibility of assessment or reporting effects after assignment. The registry record does not describe blinded endpoint adjudication or another procedure intended to limit such effects.
What can planning calculations tell readers?
In general, a sample-size calculation estimates the amount of information a proposed study might need to detect a specified effect under stated assumptions. Such a calculation is a planning illustration, not evidence that an effect was observed and not a measure of the probability that the study found a true effect. The record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. These assumptions do not establish the original design rationale, and the registry does not report a sample-size justification. No planning values are interpreted as observed power or as trial results.
For event outcomes, general methods can also be affected by over-dispersion: observed variability may exceed what a simple model assumes, making standard errors too small and intervals too narrow if the extra variability is ignored. The registry record does not say that over-dispersion was assessed or that a particular model was used for the primary endpoint. The outcome description gives a planned presentation of group counts, percentages, and confidence intervals, but not the computational method for those intervals. It would be inappropriate to infer an analysis method that is not recorded.
Finally, the primary endpoint is a composite: it can be met by different events or by discontinuation due to a listed event. In general, composite outcomes can summarize several related events but may combine events with different clinical implications or frequencies. Separate component counts would help readers understand what contributed to the composite. The registry does not report those primary-endpoint component results.
10. Multiplicity, Missing Data and Analysis Populations
The study lists a primary safety endpoint and secondary outcomes covering motor examination, dementia rating, clock drawing, neuropsychiatric symptoms, activities of daily living, and disease stage. Several of the secondary measures are scheduled at multiple follow-up points. Examining many outcomes and time points creates multiplicity: the more statistical comparisons considered, the greater the chance that some findings may appear notable by chance if no adjustment or prespecified hierarchy is used.
The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which comparisons were designated for formal testing. It also does not report interim analyses or a statistical analysis plan. It is therefore not possible to determine whether or how the study controlled the interpretation of multiple outcomes. The outcome list alone does not show which analyses were conducted or which findings, if any, were emphasized.
The primary outcome population is described as the safety population: participants who received at least one dose and had at least one post-baseline safety measurement. Participants with observation at 76 weeks were included in the analysis. The registry does not specify how missing measurements, early discontinuations unrelated to the endpoint, or other incomplete follow-up were handled. Although discontinuation due to a predefined event is part of the endpoint, the record does not explain how other reasons for discontinuation affected analysis.
Missing-data methods can influence an estimate when participants with incomplete follow-up differ from those with observed outcomes. In general, a complete-case summary describes those with the required observations and may not represent every randomized participant if missingness is related to prognosis or treatment. The record does not provide enough information to determine the extent or handling of missing primary endpoint data. Analysis populations and methods for the secondary outcomes are also not fully described in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Exelon Capsule | 87 | 294 | 29.6% |
| Exelon Patch | 83 | 288 | 28.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Exelon Capsule | 239 of 294 |
| Exelon Patch | 215 of 288 |
Most frequent serious adverse event terms
| Event term | Organ system | Exelon Capsule | Exelon Patch |
|---|---|---|---|
| Pneumonia | Infections and infestations | 9 of 294 | 7 of 288 |
| Fall | Injury, poisoning and procedural complications | 2 of 294 | 9 of 288 |
| Femur fracture | Injury, poisoning and procedural complications | 6 of 294 | 3 of 288 |
| Confusional state | Psychiatric disorders | 3 of 294 | 6 of 288 |
| Dehydration | Metabolism and nutrition disorders | 3 of 294 | 4 of 288 |
| Urinary tract infection | Infections and infestations | 2 of 294 | 4 of 288 |
| Cogwheel rigidity | Nervous system disorders | 4 of 294 | 2 of 288 |
| Syncope | Nervous system disorders | 5 of 294 | 1 of 288 |
| Hallucination, visual | Psychiatric disorders | 3 of 294 | 3 of 288 |
| Pyrexia | General disorders | 2 of 294 | 3 of 288 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Exelon Capsule | Exelon Patch |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 117 of 294 | 23 of 288 |
| Fall | Injury, poisoning and procedural complications | 48 of 294 | 49 of 288 |
| Parkinsonian rest tremor | Nervous system disorders | 69 of 294 | 26 of 288 |
| Vomiting | Gastrointestinal disorders | 45 of 294 | 7 of 288 |
| Dizziness | Nervous system disorders | 26 of 294 | 21 of 288 |
| Constipation | Gastrointestinal disorders | 21 of 294 | 21 of 288 |
| Confusional state | Psychiatric disorders | 21 of 294 | 21 of 288 |
| Diarrhoea | Gastrointestinal disorders | 27 of 294 | 14 of 288 |
| Somnolence | Nervous system disorders | 23 of 294 | 18 of 288 |
| Application site erythema | General disorders | 0 of 294 | 40 of 288 |
Serious events with the highest arm-level rate: fall (3.1%), pneumonia (3.1%), confusional state (2.1%), femur fracture (2.0%), syncope (1.7%).
The registry lists serious adverse event counts of 87 among 294 at risk for Exelon Capsule and 83 among 288 at risk for Exelon Patch. It also lists other adverse event counts of 239 among 294 and 215 among 288, respectively. These are the recorded counts and denominators; the figures should not be read as the primary motor-symptom endpoint. They also should not be converted into comparative rates without a specified analysis and careful attention to the registry’s definitions.
The most frequent serious-event terms listed are Fall and Pneumonia, each at 3.1%, followed by Confusional state at 2.1%, Femur fracture at 2.0%, Syncope at 1.7%, and Urinary tract infection at 1.4%. The registry record does not state the denominators or full counting rules for these term-specific percentages. Terms can overlap within participants, so the percentages should not be summed. These selected terms do not necessarily describe every serious adverse event in the study.
The record reports no death counts in the adverse event listing. That absence should not be interpreted as evidence that no deaths occurred; the record does not provide a death result in this listing.
12. What the Result Does, and Does Not, Mean
The registry establishes that the trial was designed to examine long-term safety of rivastigmine capsule and patch treatment in people with mild to moderately severe Parkinson’s disease dementia, with particular attention to motor-symptom worsening. It also defines a primary endpoint and describes the intended reporting of group counts, percentages, and confidence intervals. The serious adverse event counts and selected serious-event terms provide some safety information recorded for the two groups.
However, the primary endpoint results are not reported in the registry record. Without those group-specific results, it is not possible to describe the observed frequency of the predefined motor-symptom events, quantify the uncertainty around those frequencies, or assess the comparative result for capsule versus patch on that endpoint. The available serious-event listings do not fill that gap because they concern a broader safety category and selected terms, rather than the defined primary endpoint.
The existence of a randomized comparison does not by itself establish that one formulation has a more favorable safety profile. Interpretation also depends on outcome definitions, follow-up, analysis populations, missing data, and how events were assessed. Here, the study was open-label, and the registry record does not describe the method used to calculate the primary confidence intervals, the handling of missing endpoint data, or a multiplicity strategy for the range of secondary outcomes.
The record also lists secondary measures of motor function, cognition, behavior, daily activities, and disease stage. Their inclusion indicates what the study planned to assess, not what the results were. Those results are not reported in the registry record. The posted information therefore supports a description of the trial’s design and selected adverse-event listings, but does not support a full account of efficacy outcomes or a definitive comparative interpretation of the primary safety question.
These limitations concern what can be concluded from the registry record, not whether the study collected additional information elsewhere. No further result, explanation, or analysis should be assumed when it is not reported in the registry record.
13. Why This Trial Matters Statistically
This study raises a statistical question that is important in long-term safety research: how to define and interpret adverse events that may reflect worsening of the underlying disease as well as treatment-related concerns. The primary endpoint focuses on a specified set of motor symptoms and includes discontinuation due to those events. That structure makes clear why endpoint definition matters: the interpretation depends on which events count and how attribution is made.
The randomized, parallel-group design creates a direct comparison between two formulations of the same drug, while the open-label design leaves potential for differences in reporting and clinical assessment. Statistical interpretation must consider both features. Randomization can support comparability at assignment, but it cannot replace information about outcome ascertainment, follow-up completeness, or the analysis used.
The registry also illustrates the distinction between an outcome being defined and its results being available. It records the primary measure and says confidence intervals were to be presented, yet does not report the resulting counts, percentages, or intervals. Without those estimates, readers cannot evaluate either the apparent frequency of the endpoint or the precision of the comparison. A clearly specified outcome is valuable, but it cannot answer the research question without its results.
Finally, the listed secondary assessments span several clinical domains and follow-up points. This breadth can offer a fuller picture when results and analysis methods are reported, but it also makes multiplicity and missing-data handling important. The registry record does not provide enough detail to evaluate those aspects. The statistical lesson is to distinguish trial design, planned measurement, and observed results rather than treating them as interchangeable evidence.
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 registry record contains an important gap between the primary endpoint definition and its results: it describes what was to be counted and how it was to be summarized, but does not give the group-specific counts, percentages, or confidence intervals. This prevents direct interpretation of the trial’s stated primary safety question.
The record does not report the randomization sequence method or allocation concealment. It identifies the study as randomized and unmasked, but does not describe whether endpoint assessment was adjudicated independently or whether other safeguards were used to limit the effect of treatment knowledge. This is relevant because the endpoint includes judgments about whether an adverse event was due or potentially due to worsening motor symptoms.
The registry does not explain the primary confidence-interval calculation, the handling of missing observations, or the analysis of participants who discontinued for reasons other than a predefined event. Although it specifies a safety population and notes that participants with a week 76 observation were included, it does not provide the number with endpoint data or a fuller account of follow-up completeness.
The serious adverse event terms are listed with percentages, but the record does not state the corresponding denominators or counting rules for those term-specific figures. The terms may overlap, and the listed events should not be treated as mutually exclusive. The adverse event listing gives no death counts.
Several secondary outcomes are named, but their results are not reported in the registry record. Nor does the record describe a multiplicity plan, a hierarchy of outcomes, interim analyses, or the rationale for the enrollment target. The patch regimen description is incomplete at its final dose-maintenance statement. These reporting gaps limit assessment of the full protocol and the results, beyond the details explicitly recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Long-term Safety of Rivastigmine Capsule and Patch in Patients With Mild to Moderately-severe Dementia Associated With Parkinson's Disease (PDD) — NCT00623103.
- Registry record last updated 2011-11-28; status last verified 2011-10.
- Results first posted 2011-11-28.
- 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.
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18. Record Summary
The registry describes a completed Phase 3, randomized, parallel-group, open-label study of rivastigmine capsule and transdermal patch in people with mild to moderately severe Parkinson’s disease dementia. Enrollment was 583, and the study timeframe was 76 weeks.
The primary outcome was the percentage of participants with adverse events due, or potentially due, to worsening motor symptoms, or discontinuation due to tremor, muscle rigidity, bradykinesia, or fall. The registry record does not report the primary outcome results or its confidence intervals.
Serious adverse event counts and selected serious-event term percentages are recorded for both treatment groups. The registry also lists secondary clinical measures, but their results are not reported in the registry record. Details about missing-data handling, multiplicity, and several analysis methods are not reported in the registry record.