An Open-Label Extension Trial to Assess the Safety of Long-Term Treatment of Rotigotine in Advanced-Stage Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Extension Trial to Assess the Safety of Long-Term Treatment of Rotigotine in Advanced-Stage Parkinson's Disease (NCT00501969), a na phase 3 study. The primary outcome is Number of Subjects With at Least One Adverse Event During This Open-label Extension Study.

2. Clinical Question

3. Trial Design

This was a Phase 3, open-label extension study of rotigotine in advanced-stage idiopathic Parkinson’s disease. Its official title identifies it as an extension to the double-blind SP515 trial, NCT00244387. The registry lists a single-group model, allocation as NA, and masking as none. These features mean the extension does not provide a concurrent randomized comparison. Its stated objective was to assess safety and tolerability of long-term rotigotine treatment.

The registry reports enrollment of 395 and identifies the intervention as rotigotine. The study start is recorded as 2004-08, primary completion as 2008-12, and status as completed. The primary outcome timeframe is described as five years. That timeframe is the registry’s stated outcome period; the record does not establish that each participant had the same duration of exposure or observation.

The primary endpoint was the number of subjects with at least one adverse event during the extension. The registry also lists withdrawal due to an adverse event and mean Epworth Sleepiness Scale score during the open-label extension as secondary outcomes. Numerical results for those secondary outcomes are not reported in the registry record. The registry does not report the protocol’s detailed follow-up schedule, treatment-discontinuation rules, or a statistical analysis plan. These omissions limit what can be inferred about how exposure and observation were managed over the long-term period.

Because the study is open-label and single-group, its design is suited to describing recorded safety experience during treatment, not to estimating a comparative treatment effect. A comparison with the preceding double-blind study cannot be treated as a concurrent control comparison on the information reported for this extension.

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: Of the 395 subjects who entered the study, 395 are included in this summary based on the Safety Set (SS).

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 Number of Subjects With at Least One Adverse Event During This Open-label Extension Study, measured over five years.

The primary endpoint is the number of subjects with at least one adverse event during the five-year timeframe. An adverse event is defined in the registry as any untoward medical occurrence in a subject administered study treatment, whether or not the event is considered related to treatment. The endpoint therefore concerns events observed after treatment administration, not an adjudicated conclusion that treatment caused them.

As a binary participant-level outcome, each subject is classified according to whether at least one event occurred. This can give a compact account of how many participants experienced an event, but it does not describe the total number of events, their duration, severity, timing, or recurrence. Nor does it by itself distinguish events related to treatment from events that occurred during treatment for other reasons.

General statistical context: such outcomes are commonly used in safety reporting because they indicate the proportion of a study population with any recorded event. Interpretation depends on the population observed, completeness of follow-up, and consistency of event collection. The registry reports that 395 subjects entered and that 395 are included in the Safety Set summary. The primary outcome timeframe is stated as five years, but details about individual exposure and follow-up are not reported in the registry record. The posted adverse-event summary separately lists 305 in the other-event field and 148 in the serious-event field; these categories should not be conflated with an event count or with a causal estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group result estimate?

General statistical explanation: a single-group summary describes outcomes observed among participants in that group. For a binary endpoint such as having at least one adverse event, the result is a count of participants meeting the definition, sometimes accompanied by a proportion or uncertainty interval. This study’s registry record lists a single-group design and gives participant counts for serious and other adverse events. It does not provide a randomized comparison or an adjusted estimate of a difference between treatments.

Without a concurrent comparator, the event counts cannot separate treatment effects from the background occurrence of illness, changes in health over time, or other influences. A before-and-after comparison would require relevant baseline outcome data and a defined analysis, neither of which is reported in the registry record. The extension’s relation to an earlier double-blind trial does not itself make the earlier study a concurrent control for the extension.

What does “at least one event” mean?

General statistical explanation: an “at least one” endpoint counts each participant according to whether they experienced one or more qualifying events. It treats a participant with one event and a participant with repeated events as meeting the endpoint, while the count remains a count of people rather than episodes. That makes the endpoint useful for describing how widespread an event was across the group, but it does not measure recurrent-event burden or event duration.

For this trial, the primary outcome title refers to subjects with at least one adverse event, and its timeframe is given as five years. The registry’s adverse-event summary separately records serious and other events. The summary does not explain the overlap between these categories or provide enough detail to reconstruct the primary endpoint from them. The event definition includes occurrences whether or not related to treatment, so the count is not equivalent to a count of treatment-caused events.

Why do exposure and follow-up matter?

General statistical explanation: safety counts are easier to interpret when the amount of time participants are exposed and observed is known. If follow-up differs, participants may have unequal opportunities for events to be recorded. A participant-level “at least one event” summary does not account for that difference in the way a time-to-event analysis or an event rate using person-time might. The registry states a five-year timeframe, but participant-specific exposure and observation durations are not reported in the registry record. No time-to-event estimate is reported.

The record says 395 subjects entered and that 395 are included in the Safety Set summary. That inclusion statement identifies the population used for the posted summary; it does not, by itself, describe the completeness of follow-up or show that all subjects were observed for the entire timeframe. Withdrawals due to adverse events are listed as a secondary outcome, but numerical results are not reported in the registry record.

How should the serious-event percentages be read?

General statistical explanation: a percentage for a particular adverse-event term is interpretable only with an understood denominator and counting convention. It may refer to participants with the term or to another event-based quantity. Unless the denominator and method are specified, it should not be converted into a rate or directly compared across studies. The registry lists Parkinson’s disease at 4.6%, pneumonia at 1.8%, urinary retention at 1.5%, urinary tract infection at 1.3%, cardiac failure at 1.0%, and fall at 1.0% among the top serious terms. The denominator and event-count basis are not reported in the registry record.

The serious-event and other-event fields give participant counts, but the record does not state whether a subject could be counted in both. Such categories are not necessarily mutually exclusive. Therefore, their counts should be interpreted separately and not combined. The record’s deaths field is empty; mortality information is not reported in the registry record.

What can confidence intervals and tests add?

General statistical explanation: a confidence interval expresses the precision of an estimate under specified statistical assumptions. A narrow interval indicates greater precision than a wide interval, while neither interval alone establishes causation or clinical importance. A hypothesis test evaluates compatibility with a specified null hypothesis under its assumptions; a p-value is not the probability that a treatment works or that the null hypothesis is true. For a single-group safety description, an interval around an event proportion could quantify sampling uncertainty, but it would not supply a control-group contrast.

No confidence interval, p-value, or inferential analysis for the primary endpoint is reported in the registry record. The number of analyses is listed as 0. Thus, interpretation should remain descriptive rather than implying statistical significance, adjusted effects, or a precise comparative estimate.

How should planning estimates be understood?

General statistical explanation: sample-size calculations are prospective planning tools. They estimate the number of participants that might be needed under assumed effect sizes, error rates, allocation, and statistical methods. They do not measure the probability that a completed study has detected a real effect, and they are not observed power. A planning illustration based on an observed effect is especially hypothetical when the source trial has no randomized comparator, because the observed difference may not be a treatment effect.

The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. The registry record does not report a trial-specific sample-size justification. Those hypothetical planning assumptions do not change the actual single-group design, and no derived planning quantities should be read as observed results or as the trial’s original design rationale.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Rotigotine")
n      <- c(395)
events <- c(357)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Rotigotine  395  357  90.4  87.0  93.1  87.1  92.9  87.1  92.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome as the number of subjects with at least one adverse event and lists two secondary outcomes: withdrawal due to an adverse event and mean Epworth Sleepiness Scale score during the open-label extension. The registry record does not report numerical results for those secondary outcomes. It lists 0 analyses and provides no inferential analysis results for the primary outcome in the information.

Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. General statistical explanation: testing many hypotheses can increase the chance of at least one apparently notable result unless the analysis plan accounts for the family of tests. The registry record does not report an approach to multiplicity, any prespecified hierarchy among the secondary outcomes, or a statistical analysis plan. It is therefore not possible to assess whether or how multiplicity was addressed.

The population statement says that 395 subjects entered and that 395 are included in the Safety Set summary. The registry does not report the amount or pattern of missing outcome data, how missing observations were handled, or whether any imputation was used. It also does not report a separate intention-to-treat population or other analysis populations. The Safety Set label should be understood as the population identified for this summary; no additional eligibility or analysis rules are specified in the registry record.

These omissions matter because adverse-event findings depend on who was observed, for how long, and how missing observations were treated. The five-year timeframe does not establish equal follow-up for all participants. Without the missing-data and follow-up details, the summary can be read as a record of the posted Safety Set counts, but cannot establish complete event ascertainment over the full timeframe.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: parkinson's disease (4.6%), pneumonia (1.8%), urinary retention (1.5%), urinary tract infection (1.3%), cardiac failure (1.0%).

The registry’s adverse-event summary gives 395 at risk in the rotigotine group for both the serious-event and other-event fields. It records 148 affected in the serious-event field and 305 affected in the other-event field. These are participant counts as presented in the registry; they are not counts of event episodes. The record does not state whether the same participant can appear in both fields, so the numbers should be read separately, not added.

The listed serious-event terms are Parkinson’s disease at 4.6%, pneumonia at 1.8%, urinary retention at 1.5%, urinary tract infection at 1.3%, cardiac failure at 1.0%, and fall at 1.0%. The percentages do not by themselves indicate the number of episodes, severity beyond the serious-event classification, timing, or relation to treatment. The denominator and counting basis for these term percentages are not reported in the registry record.

Serious adverse events are not necessarily events caused by treatment. The registry’s general adverse-event definition explicitly includes events whether or not related to treatment. The empty deaths field does not establish that no deaths occurred; mortality details are not reported in the registry record. The summary is descriptive and has no concurrent control group for judging whether these observations differ from another treatment or background experience.

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

The results describe adverse events recorded in a completed, open-label extension of rotigotine treatment for advanced-stage idiopathic Parkinson’s disease. The registry identifies 395 subjects entering the study and reports that the same number were included in the Safety Set summary. It lists separate serious-event and other-event participant counts, along with selected serious-event terms and percentages. These findings provide a description of the safety information captured in this single-group extension.

They do not establish that rotigotine caused any particular event. The adverse-event definition includes untoward medical occurrences whether or not related to treatment, and the design has no concurrent control group. The counts cannot show what would have happened to comparable participants under another treatment. Nor do the counts alone indicate event timing, recurrent episodes, duration, or individual exposure time.

The record’s primary endpoint concerns at least one adverse event over a five-year timeframe. The record does not report participant-specific follow-up or explain the relationship between the primary endpoint and the separate serious-event and other-event categories. It also does not report confidence intervals, p-values, an inferential analysis, or numerical results for the listed secondary outcomes. Consequently, the posted counts and term percentages should not be taken as a comparative estimate or a complete account of uncertainty.

General statistical context: an uncontrolled safety extension can document events among participants who enter and remain under observation, and can identify event categories for further consideration. It cannot, by itself, distinguish effects of treatment from the course of the underlying condition or other influences. A lack of reported event details is not evidence that an event did not occur; it means that the detail is not reported in the registry record.

The study’s stated purpose and design support a descriptive reading of long-term safety observations. They do not support a claim of efficacy, a conclusion that treatment is safe or unsafe in general, or a comparison with other therapies. The results apply to the registry’s described study group and reporting, with the limitations of the available follow-up and analysis details.

14. Why This Trial Matters Statistically

This trial is statistically informative because its purpose and design make the distinction between safety description and comparative inference especially important. It was an open-label extension with one rotigotine group, not a randomized comparison. The data can describe reported adverse events in the study population, but there is no concurrent group to estimate how event experience might differ under another condition.

The primary endpoint is a participant-level binary outcome: whether a subject had at least one adverse event during the stated five-year timeframe. That summary is easy to interpret as a count of people with an event, but it does not reveal how often events recurred, how long they lasted, or when they occurred. The registry’s separate serious-event and other-event counts highlight why outcome definitions and category overlap matter. They should not be added or assumed to represent disjoint groups.

The record also illustrates the distinction between a stated study timeframe and observed participant follow-up. The registry says 395 subjects entered and 395 are included in the Safety Set summary, but does not report individual exposure time or follow-up completeness. These details influence how a long-term safety count should be understood.

Finally, the registry lists secondary outcomes but does not report their numerical results, and it does not provide an analysis plan, missing-data approach, or multiplicity procedure. Recognizing these gaps prevents descriptive counts from being mistaken for a complete inferential analysis. The most defensible interpretation stays close to what the registry records: an account of adverse events in a single-group extension, with limited information for assessing precision, completeness, or causality.

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.

The principal limitation is the absence of a concurrent comparator. The trial is listed as single-group, open-label, with allocation as NA and masking as none. Its adverse-event counts therefore cannot estimate a relative risk or treatment difference. The extension’s connection to the earlier double-blind SP515 study does not supply a concurrent control group for this record.

Follow-up and exposure details are limited. The primary outcome timeframe is five years, but participant-specific time on treatment and time under observation are not reported in the registry record. The record states that 395 subjects entered and that 395 are included in the Safety Set summary, but it does not provide a participant flow account or explain how the full follow-up period was achieved.

The adverse-event reporting also leaves interpretive questions. The registry gives serious-event and other-event participant counts, but does not report whether categories overlap. It lists percentages for selected serious-event terms without reporting the denominator or counting basis. The deaths field is not populated, and mortality details are not reported in the registry record. The primary endpoint’s numerical result is not explicitly mapped to the separate adverse-event categories in the available information.

Numerical results for the listed secondary outcomes are not reported in the registry record. The record also does not report confidence intervals, p-values, methods for handling missing data, an analysis plan, or a multiplicity approach. These omissions limit evaluation of precision, completeness, and the robustness of any inferential claim. They do not invalidate the descriptive counts, but they narrow what those counts can support.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open-Label Extension Trial to Assess the Safety of Long-Term Treatment of Rotigotine in Advanced-Stage Parkinson's Disease — NCT00501969.
• Registry record last updated 2014-10-02; status last verified 2012-03.
• Results first posted 2010-01-12.
• 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 record describes a completed Phase 3, open-label, single-group extension of rotigotine in advanced-stage idiopathic Parkinson’s disease. The official title identifies it as an extension to the double-blind SP515 trial, NCT00244387. Enrollment is 395; the start is recorded as 2004-08 and primary completion as 2008-12.

The primary outcome is the number of subjects with at least one adverse event during five years. The record states that all 395 subjects who entered are included in the Safety Set summary. Its adverse-event summary lists 148 in the serious-event field and 305 in the other-event field, with selected serious-event terms and percentages. There is no concurrent comparator. Numerical results for the listed secondary outcomes, inferential analyses, and details on missing data and individual follow-up are not reported in the registry record.