Open Label Continuation Treatment Study With Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open Label Continuation Treatment Study With Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease (NCT00660673), a na phase 3 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events.

2. Clinical Question

The study’s stated primary objective was continued access to LCIG for participants who had taken part in earlier open-label efficacy and safety studies. The endpoint is safety-focused: it counts participants with TEAEs, rather than measuring a change in motor symptoms or comparing treatment efficacy. The record also lists secondary safety outcomes, including device complications, sleep attacks, intense impulsive behavior, melanoma, suicidality, vital-sign values, and hematology laboratory values. The information reported does not establish how those outcomes compare with what would have occurred without continued treatment. Because participants entered after prior treatment and a persistent positive effect, interpretation applies to this continuation setting and should not be generalized automatically to people starting LCIG for the first time.

3. Trial Design

This was a completed Phase 3, open-label continuation study, registered as NCT00660673. It enrolled 262 participants with advanced Parkinson’s disease. The stated objective was to provide continued access to LCIG for participants who had already taken part in one of two earlier open-label studies of the same treatment. The study began on 2009-11-13, and primary completion was recorded as 2021-11-30.

The design was single-group, with no masking and no allocation to a concurrent control arm. The intervention was LCIG, administered using an ambulatory infusion pump and PEG-J tube. Initial dosing followed the participant’s previous LCIG study regimen, with individual adjustment during the study as clinically indicated. The registry describes the treatment as open-label, so participants and study personnel were not masked to treatment assignment.

The primary outcome was the number of participants with TEAEs. The defined period ran from the first LCIG infusion in this study until 30 days after the last PEG-J exposure. The registry reports a median treatment duration of 1178 days and a maximum of 4217 days (11.5 years). This extended follow-up provides a record of events over continuing exposure, but the duration varied between participants.

Because the study was a continuation cohort without a concurrent control group, its design supports descriptive reporting of events among participants who continued LCIG. It does not provide a randomized comparison with another treatment or with no treatment. The registry record does not report a sample-size justification, a detailed statistical analysis plan, interim analyses, or a protocol for handling changes in exposure beyond the stated dosing description.

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.

Before assignment: This study was an open-label extension study for participants with Parkinson's disease (PD) who had completed one of the prior studies S187.3.003 (NCT00360568) or S187.3.004 (NCT00335153). Participants were to receive continued access to levodopa-carbidopa intestinal gel (LCIG) in the extension study until treatment became commercially available in their home country.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received LCIG in this extension 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 Number of Participants With Treatment-emergent Adverse Events, measured over From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days, with a maximum of 4217 days (11.5 years)..

The primary endpoint is the number of participants with treatment-emergent adverse events. A TEAE is defined as an adverse event that started on or after the first LCIG infusion in this study and within 30 days of the last PEG-J exposure. The endpoint therefore summarizes whether participants experienced at least one event meeting that definition during their individual observation period; it is not a rate per unit of time or a measure of event severity alone.

The endpoint is used to describe safety during continued treatment. The registry further classifies whether events were assessed as at least possibly related to study drug, whether they were serious, and whether their severity was mild, moderate, or severe. Serious events include specified outcomes such as death, a life-threatening event, hospitalization or prolonged hospitalization, persistent or significant disability, or a congenital anomaly or birth defect. These definitions help distinguish event categories, but they do not by themselves establish that treatment caused an event.

The reported primary endpoint population is all participants who received LCIG in the extension study. The registry record does not report a comparative estimate for this endpoint, nor does it report an efficacy endpoint as the primary outcome. A participant count is useful for describing how many people had events in this cohort, while leaving event timing, repeated events, and comparative risk questions unresolved unless separately analyzed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a participant count: it records whether a participant had one or more events meeting the TEAE definition during the specified period. In general, participant counts answer how many people were affected, whereas event counts can include repeated events in the same person. The registry characterizes the primary outcome as a count of participants. It does not report the number of repeated events for that endpoint in the information available for this analysis.

What does a single-group estimate describe?

In general, a single-group safety summary describes observed outcomes among people receiving the intervention. It can characterize the kinds of events recorded and how many participants were affected. A treatment effect, by contrast, requires a defined comparison: for example, a difference in outcome between intervention and control groups. Here, the registry identifies a single-group model and no randomized comparison. Thus the reported counts are descriptive, not estimates of a difference attributable to LCIG.

Randomization is useful in comparative trials because it can balance, on average, measured and unmeasured factors between groups. This study’s continuation design does not use random allocation to treatment groups. The record says participants had already taken part in earlier LCIG studies, so eligibility and participation reflect a prior-treatment context. That selection can limit how well the cohort represents patients who were not in the earlier studies or who did not continue into the extension.

How should follow-up duration affect reading?

In general, a participant count does not incorporate the amount of time each person was observed. Someone followed for a longer period has more opportunity to experience an event than someone followed for a shorter period. The registry reports a median treatment duration of 1178 days and a maximum of 4217 days (11.5 years), indicating extended follow-up but not uniform exposure duration. A time-to-event analysis or an incidence rate could address time at risk in other ways, but such an estimate for the primary endpoint is not reported in the registry record.

The endpoint’s observation window has a specific boundary: it starts on or after the first LCIG infusion and includes events within 30 days after the last PEG-J exposure. This definition determines which events qualify as treatment-emergent for the outcome. It does not prove causation. The registry’s definition of at least possibly drug-related includes events assessed as possible or probable, or with a missing relationship assessment. Relationship assessment and temporal classification are distinct from demonstrating that treatment caused an event.

What do precision and statistical testing add?

In general, a confidence interval expresses uncertainty around an estimate under a statistical model. A narrow interval indicates greater precision than a wide interval, while an interval does not remove biases in study design or establish causality. No confidence interval for the primary endpoint is reported in the registry record. No primary-endpoint hypothesis test or comparative effect estimate is reported either. The participant counts can therefore be read as observed descriptions, but not as a complete account of statistical precision.

In general, a p-value evaluates how compatible observed data are with a specified statistical model and null hypothesis. It does not measure the probability that a treatment works, and it is not a measure of clinical importance. Because no relevant primary-endpoint p-value or null hypothesis is reported, statistical significance cannot be inferred from the counts alone.

How should the planning illustrations be interpreted?

The registry’s planning assumptions describe illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not evidence that the continuation study itself had two arms or was designed using those assumptions. In general, a sample-size calculation estimates the amount of information a hypothetical design might require under stated assumptions. It is not observed power and cannot repair the absence of a concurrent comparator in this study.

The record does not report a sample-size justification for the actual extension study. It also does not report the statistical method used to calculate uncertainty for the primary count. Therefore, planning illustrations should not be mistaken for the study’s original design rationale or for a test of the observed safety results.

What does seriousness mean?

The registry defines serious adverse events by specified medical consequences, including death, life-threatening events, hospitalization or prolonged hospitalization, persistent or significant disability, or congenital anomaly or birth defect. Seriousness is a regulatory classification based on outcome or consequence; it is not the same as severity. The stated severity categories are mild, moderate, and severe, based on effects on daily activity and degree of inconvenience or concern. An event can be serious without being described as severe under the stated severity scale, and vice versa. These classifications describe events and do not independently establish treatment attribution.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures and 6 analyses. It does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a plan specifying which analyses were confirmatory. When several outcomes or tests are examined, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can control that risk, but whether such procedures were used is not reported in the registry record. The number of listed outcomes alone does not establish that any particular adjustment was necessary or applied.

The primary endpoint population is described as all participants who received LCIG in the extension study. The registry does not give details about missing outcome data, participants who withdrew, how incomplete follow-up was handled, or whether any analysis population differed from the stated primary population. These details are important because missing outcomes can affect descriptive counts and comparative estimates. No imputation method or sensitivity analysis for missing data is reported in the registry record.

The record also does not report a detailed statistical analysis plan, interim-analysis procedures, or a sample-size justification. It describes a single-group, open-label study with no concurrent control comparison, so the reported outcome counts should be interpreted as descriptive. The planning assumptions associated with sample-size illustrations do not establish the analysis plan used for this completed study. Without further analysis details, the registry information does not support conclusions about multiplicity control, missing-data robustness, or prespecified testing procedures.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (7.6%), complication of device insertion (5.3%), death (5.0%), fall (5.0%), postoperative wound infection (3.4%).

The registry’s safety summary lists 159 participants with serious adverse events and 223 with other adverse events in the LCIG group, with 262 participants at risk. These are participant counts, not counts of all separate event episodes. A participant may have experienced more than one event, and the summary does not reveal repeated-event patterns. The record separately lists 59 deaths. The serious-event terms include pneumonia at 7.6%, complication of device insertion at 5.3%, death at 5.0%, fall at 5.0%, postoperative wound infection at 3.4%, and pneumonia aspiration at 3.4%.

These figures describe events observed during an open-label continuation study with long and variable exposure. They do not establish that LCIG caused an event, and they do not show what event frequency would have been under a comparator. The serious-event classification is based on defined consequences such as death, life-threatening events, or hospitalization; it is separate from the mild, moderate, and severe event-intensity categories. The registry record does not report a comparative safety analysis or confidence intervals for these figures, so their interpretation is descriptive rather than causal or comparative.

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

The posted results establish that adverse events, including serious events and deaths, were recorded among participants continuing LCIG in this extension study. The primary endpoint is a count of participants with TEAEs over a defined period of exposure. The safety summary also gives participant counts for serious and other adverse events and lists several serious-event terms with percentages. These observations are relevant to describing the experience of this cohort during ongoing treatment.

They do not establish that LCIG caused the recorded events. Advanced Parkinson’s disease and other circumstances may also contribute to events, but the registry record does not quantify those contributions. Without a concurrent comparator, the study cannot show whether the observed counts are higher, lower, or similar to what would have occurred under another treatment or without continued LCIG. The figures also do not establish an effect on symptoms, function, or quality of life, because the primary outcome is safety-focused.

The population was drawn from participants who had already taken part in earlier open-label LCIG studies, and the stated aim was to provide continued access. The results therefore describe a continuation setting and should not automatically be generalized to people starting LCIG, to people who did not enter the extension, or to all people with advanced Parkinson’s disease.

Follow-up was extended, but duration varied. A participant count does not account directly for differences in time exposed, and no comparative time-to-event result or confidence interval for the primary outcome is reported in the registry record. The data can inform a descriptive understanding of reported events in this cohort, but they do not settle questions of causation, comparative risk, or treatment benefit.

13. Why This Trial Matters Statistically

This study is statistically informative because it illustrates the distinction between a long-running safety description and a comparative treatment-effect estimate. A single-group extension can document which adverse events were recorded among people continuing treatment, including serious events over extended exposure. Its participant counts serve a descriptive purpose and do not require a randomized control group to be understood as observations in the cohort.

At the same time, the design sets clear limits on inference. Without a concurrent comparator, the event counts cannot distinguish treatment-related risk from the background risk of illness, other care, or chance. The open-label design and prior-study participation further define the population to which these observations apply. The continuation setting is not equivalent to a trial of treatment initiation in a broader population.

The endpoint also emphasizes the importance of matching the statistic to the question. Counting participants with events conveys how many people were affected in the observed cohort. It does not fully characterize repeated events, timing, or differences in exposure duration. The reported median and maximum duration give context for prolonged follow-up, but a participant count alone does not adjust for time at risk.

Finally, the record’s lack of reported confidence intervals, comparative estimates, multiplicity procedures, and missing-data methods limits the assessment of precision and robustness. These omissions do not erase the descriptive information; they define what the registry record can support. The central statistical lesson is to separate observed safety experience from causal or comparative claims and to interpret every count in light of the study population and design.

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 main limitation specific to this trial is its single-group, open-label continuation design. There is no concurrent control group, so adverse-event counts cannot be interpreted as comparative risks. The record also does not report random allocation or masking. These design features restrict causal interpretation and make it impossible to isolate the effect of continued LCIG from other influences using the reported summaries alone.

Participants had already been involved in prior open-label studies of LCIG, and the extension’s stated purpose was continued access. This makes the cohort selected by prior participation and continuation. Its experience may not represent people who have not previously received LCIG or who did not enter the extension. The registry does not report how participants who discontinued differed from those who continued.

Follow-up duration varied, with a median treatment duration of 1178 days and a maximum of 4217 days (11.5 years). The available participant counts do not account for this variation in time at risk or detail repeated events. The registry record does not report a primary-endpoint confidence interval, comparative effect estimate, detailed analysis method, sample-size justification, interim-analysis plan, multiplicity procedures, or methods for missing data. These omissions limit assessment of precision, robustness, and the role of prespecification.

The safety categories and event definitions clarify what was counted, but they do not establish causality. The record describes how adverse events were classified by seriousness, severity, and relationship to study drug; those assessments remain distinct from evidence based on a controlled comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open Label Continuation Treatment Study With Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease — NCT00660673.
• Registry record last updated 2022-12-02; status last verified 2022-11.
• Results first posted 2022-12-02.
• 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

NCT00660673 is a completed Phase 3, open-label, single-group continuation study of LCIG in advanced Parkinson’s disease. It enrolled 262 participants who had taken part in earlier open-label LCIG studies. The stated objective was continued access to treatment. The registry records a start date of 2009-11-13 and primary completion on 2021-11-30.

The primary outcome was the number of participants with TEAEs, defined over the period from first LCIG infusion through 30 days after last PEG-J exposure. Median treatment duration was 1178 days, with a maximum of 4217 days (11.5 years). The adverse-event summary lists 159 participants with serious events, 223 with other events, and 59 deaths in the LCIG group.

The study provides descriptive safety information for a selected continuation cohort. The registry record does not report a concurrent comparator, comparative effect estimates, confidence intervals for the primary endpoint, or detailed methods for missing data and multiplicity. The counts therefore do not establish treatment causation or comparative risk.