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 Relative Bioavailability Study of Ropinirole Implants in Parkinson's Patients on L-Dopa Switched From Oral Ropinirole (NCT03250117), a non-randomized phase 1, phase 2 study. The primary outcome is AUC0-24 Hours of Ropinirole.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03250117 |
| Phase | Phase 1, Phase 2 |
| Condition | Parkinson Disease |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Titan Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
People with Parkinson disease who were stable on L-Dopa and oral ropinirole. The planned pharmacokinetic population included participants who received at least one ropinirole implant and had at least one pharmacokinetic parameter of interest that could be calculated.
Intervention
Ropinirole delivered through an implant inserted under the skin. The study described cohorts receiving one, two, three, or four ropinirole implants after use of oral Requip.
Comparator
Participants were switched from oral immediate-release ropinirole to implants in a non-randomized, sequential study. The registry record does not describe a randomized or like-for-like control comparison.
Primary question
What was the 0-24 hours area under the plasma concentration-time curve for ropinirole during implant treatment? The registry record states that this planned analysis was not performed because representative samples from each cohort were insufficient.
3. Trial Design
NCT03250117 was an open-label, non-randomized, sequential study listed as Phase 1 and Phase 2. It enrolled 6 participants and was conducted among people with Parkinson disease who were taking L-Dopa and oral ropinirole. Participants stable on those medicines were to have oral ropinirole replaced with ropinirole implant treatment. The implant was designed using ProNeura implant technology and inserted under the skin.
The registry describes four cohorts: Cohort 1 received Requip and one ropinirole implant; Cohort 2 received Requip and two implants; Cohort 3 received Requip and three implants; Cohort 4 received Requip and four implants. The record does not give cohort enrollment counts or explain how participants were assigned to cohorts. Because allocation was non-randomized and the study was sequential, the cohorts should not be treated as randomized comparison groups. Masking was absent, so the study was open-label.
The study aimed to measure ropinirole released into the blood during 12 weeks of implant treatment and to evaluate side effects. Its primary outcome was the area under the plasma drug concentration-time curve for ropinirole over 0-24 hours. Listed secondary outcomes included pharmacokinetic measures for two metabolites and changes in MDS-UPDRS total score and awake time “On” and “Off.” The registry lists 7 outcome measures and 0 analyses.
The study started on 2017-10-10, had a primary completion date of 2018-05-22, and is listed as terminated. The reason for termination and further details about the sequence or timing of cohort enrollment are not reported in the registry record.
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: Of 6 screened patients, 3 did not meet eligibility criteria for cohort assignment.
Requip IR [7-10 Days]
| Stage | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|
| STARTED | 3 | 0 | 0 | 0 |
| COMPLETED | 3 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Ropinirole Implant 12 Weeks
| Stage | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|
| STARTED | 3 | 0 | 0 | 0 |
| COMPLETED | 2 | 0 | 0 | 0 |
| NOT COMPLETED | 1 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|
| At request of Sponsor, regulatory agencies, or the IRB | 1 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.
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 | Cohort 1 |
|---|---|---|
| Participants analysed | 3 | |
| Age, Continuous | years | 52.7 (47 to 58) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| MDS-UPDRS Total Score | units on a scale | 60.7 (23 to 97) |
| Awake Time "On" | hours | 11.54 (9.9 to 14.3) |
| Awake Time "Off" | hours | 5.02 (3.4 to 6.1) |
6. Primary Endpoint
The registry lists the primary outcome as AUC0-24 Hours of Ropinirole, measured over 0-24 hours.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was AUC0-24 Hours of Ropinirole: the area under the plasma drug concentration-time curve over 0-24 hours. In general, an area-under-the-curve measure summarizes drug concentrations across a defined time interval. For a pharmacokinetic study, it can describe systemic exposure over that interval and support assessment of how a formulation delivers drug into the bloodstream.
The registry describes the intended population as participants who received at least one ropinirole implant and for whom at least one pharmacokinetic parameter of interest could be calculated. However, the registry explicitly states that the analysis was not performed because there were insufficient representative samples from each cohort. No endpoint estimate, unit, dispersion measure, or cohort-level result is reported in the registry record.
The endpoint therefore identifies the type of pharmacokinetic information the study planned to assess, but it does not provide an observed estimate of exposure. A 0-24 hours AUC also concerns exposure during that specified interval; on its own, it does not describe the full release profile across the entire 12 weeks of intended implant treatment or establish comparative clinical effects.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical result is that the planned primary pharmacokinetic analysis was not performed. The registry attributes this to insufficient representative samples from each cohort. Consequently, there is no reported AUC0-24 Hours estimate for ropinirole, and no reported uncertainty measure such as a standard deviation or confidence interval. The record does not give cohort-specific pharmacokinetic values or an inferential comparison between implant regimens.
This absence is important to interpretation. A study can describe its planned endpoint and intended analysis population without producing an analyzable result. In this case, the endpoint definition indicates what the investigators intended to quantify, but the registry does not report a numerical estimate of ropinirole exposure. It is therefore not possible to determine from the posted results how the measured exposure varied across cohorts or how precisely it was estimated.
The study was non-randomized, open-label, and sequential. Even if cohort-specific results had been reported, differences between cohorts would not automatically be attributable to the number of implants: the registry does not describe random assignment, and the record does not establish that groups were otherwise comparable. The registry's own note also identifies the arms as not being a like-for-like control comparison. A causal comparison between implant regimens or between implant and oral treatment is not supported by the design information recorded.
The enrollment was 6, while cohort enrollment counts are not reported in the registry record. This small overall enrollment and the stated lack of representative samples are relevant to the feasibility of estimating pharmacokinetic quantities across the cohorts. They do not, by themselves, show what any individual participant's exposure was or explain why the planned analysis could not be completed.
The record lists 7 outcome measures and 0 analyses. It also lists several secondary outcomes, including metabolite AUC measures and changes in motor score and awake time. The registry does not report results for these outcomes in the information recorded. The study is marked terminated, but a reason for termination is not reported in the registry record. Taken together, the record describes a planned study question and some safety counts, but does not present the primary pharmacokinetic result needed to answer that question.
9. Statistical Methods Explained
What does the primary measure mean?
In general, pharmacokinetic studies describe how a drug concentration changes over time. AUC, or area under the concentration-time curve, is a summary of concentration across a specified interval. The planned endpoint in this study was ropinirole AUC over 0-24 hours. AUC is useful because it condenses measurements taken at different times into a measure of exposure over that interval. It does not, by itself, describe every feature of a concentration-time profile, such as the timing of a peak.
The registry specifies plasma concentration and the 0-24 hours interval, but does not report a unit or a numerical result. It also says the analysis was not performed because representative samples from each cohort were insufficient. A defined endpoint is not equivalent to an estimate: without the reported analysis, the registry does not give a value or its precision.
Why does representative sampling matter?
In general, pharmacokinetic estimates rely on concentration measurements that adequately characterize the intended population and sampling design. When samples are not sufficiently representative across groups, an estimate may not reliably characterize the intended cohort or support comparisons between cohorts. The registry gives insufficient representative samples from each cohort as the reason the primary analysis was not performed. It does not give further detail about which samples were missing, how many observations were available, or what criteria were used to judge representativeness.
The planned analysis population was restricted to participants who received at least one implant and had at least one pharmacokinetic parameter of interest that could be calculated. This identifies an intended analysis population, but the registry does not report how many participants met those criteria. It also does not describe whether participants with incomplete measurements were excluded from other outcomes or how missing observations were handled.
How should the cohort structure be understood?
The study is described as non-randomized and sequential, with four cohorts characterized by one, two, three, or four implants. In general, random allocation can help balance known and unknown participant characteristics across treatment groups. Without randomization, groups may differ for reasons other than their assigned treatment. A sequential design can also mean groups are studied in an ordered process, but the registry does not report the detailed sequence, decision rules, or assignment procedure. The cohort labels alone do not establish that implant counts were the only systematic difference between groups.
Open-label means masking was absent. In general, knowledge of treatment can influence participant reports, clinical assessments, or decisions about data collection. This is particularly relevant to outcomes based on assessment or reported symptoms. The registry does not say whether any outcome assessment procedures were designed to limit such influence.
What do statistical significance and confidence intervals add?
In general, a confidence interval expresses the range of estimates compatible with the observed data and the method used, under its assumptions. Its width conveys precision: wider intervals indicate less precise estimates, while narrower intervals indicate more precision. A statistical test and its p-value address compatibility between data and a specified null hypothesis, under the test's assumptions; they do not measure the size or clinical importance of an effect.
No primary AUC estimate, confidence interval, standard error, or p-value is reported in the registry record. There is therefore no inferential result to interpret for the primary endpoint. The absence of a reported test is consistent with the registry statement that the planned primary analysis was not performed; it should not be read as a finding of no difference or no exposure.
What do planning sample sizes mean?
In general, a sample-size calculation describes the number of participants or events a hypothetical study might require under specified assumptions. The planning illustration described in the record uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It is a planning illustration, not an observed trial result or observed power. The registry's own sample-size justification is not reported in the registry record, and no observed primary effect is reported for this study. The planning assumptions therefore cannot substitute for a completed estimate or establish what the study was designed to detect.
For time-to-event settings, event counts may be the relevant planning quantity; for other settings, planning may be expressed as participants per arm. Those general distinctions do not create a result for this study. The record does not report a time-to-event primary outcome, a reported sample-size target, or an inferential analysis of the primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures and 0 analyses. It identifies the primary ropinirole AUC endpoint and lists secondary outcomes for AUC of N-despropyl ropinirole, AUC of 7-hydroxy ropinirole, change from baseline in MDS-UPDRS total score, and change from baseline in awake time “On” and “Off.” The multiplicity strategy for evaluating several outcomes is not reported in the registry record. In general, when multiple outcomes or comparisons are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. No adjustment method or hierarchy of secondary outcomes is reported.
The planned primary analysis was not performed because representative samples from each cohort were insufficient. The registry does not report the number of missing pharmacokinetic samples, reasons for missingness, or a method for handling missing data. It also does not state whether any imputation, sensitivity analysis, or alternative analysis was planned or conducted. These details are not reported in the registry record.
The intended primary analysis population included people who received at least one implant and had at least one pharmacokinetic parameter that could be calculated. The number meeting this definition is not reported in the registry record. The record does not provide analysis populations for the secondary outcomes, participant flow by cohort, or the number contributing data to each outcome. Without those details, the extent and handling of missing outcome data cannot be assessed.
The registry's listed planning assumptions do not describe a multiplicity correction or a missing-data method. Nor do they establish that a powered, randomized comparison was part of the trial's own design. The study's statistical analysis plan, including any prespecified approach to multiplicity and missing data, is not reported 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 |
|---|---|---|---|
| Cohort 1 | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 | 0 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cohort 1 | 2 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 |
|---|---|---|
| Implant site reaction | General disorders | 1 of 3 |
| Freezing phenomenon | Nervous system disorders | 1 of 3 |
| Affect lability | Psychiatric disorders | 1 of 3 |
| Hallucination, visual | Psychiatric disorders | 1 of 3 |
The adverse-event figures reported for Cohort 1 show 3 participants at risk for serious adverse events, 0 affected by a serious adverse event, and 0 deaths. For other adverse events, 3 participants were at risk and 2 were affected. These counts describe the entries reported for Cohort 1; the registry does not provide corresponding cohort-level figures for the other cohorts in this record.
These are counts, not rates or comparisons. The record does not report exposure-adjusted summaries, event timing, severity details for the other events, or a comparison with oral ropinirole. It also does not list serious-event terms. The lack of a reported serious event among the Cohort 1 participants at risk should not be interpreted as establishing the absence of risk in a larger population or across all cohorts.
The study enrolled 6 participants overall, but the number of participants at risk shown in the safety entry is specific to Cohort 1. The registry does not provide enough detail to reconcile safety counts across all cohorts or to characterize the full safety experience for all enrolled participants. These figures are descriptive registry entries and do not support a treatment-effect conclusion.
12. What the Result Does, and Does Not, Mean
The registry record establishes that an open-label, non-randomized, sequential study of ropinirole implants was conducted among people with Parkinson disease taking L-Dopa and oral ropinirole. It describes a planned pharmacokinetic endpoint, a 0-24 hours AUC for ropinirole, and four cohorts defined by implant count. It also reports a limited set of safety counts for Cohort 1.
The primary result needed to quantify ropinirole exposure is not reported. The registry states that the analysis was not performed because representative samples from each cohort were insufficient. No AUC value, precision estimate, or cohort comparison is available in the record. The listed secondary outcomes likewise have no reported results in this record.
This means the registry entry cannot establish the magnitude or variability of ropinirole exposure during implant treatment, nor can it determine whether exposure differed across the cohorts. It also cannot establish a comparative effect of implants versus oral treatment: the recorded design was not randomized and the arms are not described as a like-for-like control comparison. No clinical effectiveness conclusion follows from an unperformed primary pharmacokinetic analysis.
The safety figures are limited to the reported Cohort 1 counts. They do not characterize the full safety experience across all participants or provide a comparative safety analysis. The study's terminated status is recorded, but its reason is not reported in the registry record.
In general, a registry entry can document a study's purpose, design, and reported results without supplying every detail needed to assess conduct or analysis. Here, the most important interpretive boundary is the absence of the planned primary estimate. The design and safety information provide context, but they do not fill that gap or turn the study into a completed comparative efficacy evaluation.
13. Why This Trial Matters Statistically
This study matters statistically because it illustrates the difference between defining a measurable endpoint and obtaining a result for it. The primary endpoint is clearly identified as ropinirole AUC over 0-24 hours, and the intended population is described. Yet the registry says the analysis was not performed because samples were insufficiently representative across cohorts. Without an estimate and its uncertainty, the pharmacokinetic question remains unanswered in the posted record.
The design also makes the distinction between a treatment sequence and a controlled comparison important. Participants were not randomized, masking was absent, and the study was sequential. The four cohort descriptions identify different implant counts, but the record does not establish that these groups are comparable or that a difference in their measurements could be attributed solely to implant count. This is why design details matter when interpreting any numerical comparison.
Finally, the entry separates descriptive safety counts from formal inference. Cohort 1 has reported counts for serious and other adverse events, but those figures are not a comparative estimate and do not describe all cohorts. With 6 participants enrolled overall and no primary analysis, the record is most informative about the study's intended question and its analysis limitation, rather than an estimate of treatment effect or a precise characterization of exposure.
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 primary endpoint has no reported numerical estimate because the planned analysis was not performed. The stated reason is insufficient representative samples from each cohort. The registry does not explain the sampling shortfall in further detail, report the amount of usable pharmacokinetic data, or provide a precision estimate.
Enrollment was 6, and cohort-specific enrollment numbers are not reported in the registry record. The record therefore does not show how participants were distributed across the four cohorts or how many contributed data to each endpoint. It describes the study as non-randomized, sequential, and open-label, but does not provide detailed allocation procedures, cohort sequencing, or masking procedures beyond stating that masking was absent.
The registry lists 7 outcome measures, while the record includes no analyses. Results for secondary outcomes are not reported. Prespecified analysis methods, missing-data handling, multiplicity procedures, and the registry's own sample-size justification are not reported in the registry record. The planning assumptions described in the record do not replace those missing trial-specific details.
Safety reporting is limited: the listed adverse-event counts are for Cohort 1, and serious-event terms are not listed. The record does not provide a full account of adverse events across cohorts or a comparative safety analysis. Although the study is marked terminated, the reason for termination is not reported in the registry record. These limitations constrain interpretation of both the planned pharmacokinetic question and the reported safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Relative Bioavailability Study of Ropinirole Implants in Parkinson's Patients on L-Dopa Switched From Oral Ropinirole — NCT03250117.
- Registry record last updated 2023-05-06; status last verified 2023-04.
- Results first posted 2023-05-06.
- 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
NCT03250117 was an open-label, non-randomized, sequential Phase 1 and Phase 2 study of ropinirole implants in people with Parkinson disease taking L-Dopa and oral ropinirole. It enrolled 6 participants and described cohorts receiving one, two, three, or four implants. The primary endpoint was ropinirole AUC over 0-24 hours, but the registry states that its analysis was not performed because representative samples from each cohort were insufficient. The record lists 7 outcome measures and 0 analyses. Cohort 1 safety figures include 0 serious adverse events and 0 deaths among 3 participants at risk, and 2 participants affected by other adverse events among 3 at risk. The study is marked terminated; the reason is not reported in the registry record.