Study of Safety, Tolerability, Pharmacokinetics, and Efficacy of ABT-SLV187 in Subjects With Advanced Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Safety, Tolerability, Pharmacokinetics, and Efficacy of ABT-SLV187 in Subjects With Advanced Parkinson's Disease (NCT01479127), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period.

2. Clinical Question

The central statistical question is descriptive: what adverse events were recorded among participants receiving oral levodopa-carbidopa during run-in and among those receiving intestinal gel, and how much can those counts establish? The registry reports small groups and does not describe a randomized treatment comparison. Therefore, counts can describe what occurred in the recorded groups, but they cannot isolate a treatment effect from differences in exposure, timing, or participant characteristics.

The study’s broad aims included safety, tolerability, pharmacokinetics, and efficacy. However, the primary endpoint specifically concerns adverse events during run-in. The listed efficacy-related outcomes are secondary measures; numerical results for those outcomes are not reported in the registry record summarized for this analysis. The focus is therefore on the structure and interpretation of the safety evidence, not on drawing a conclusion about efficacy.

3. Trial Design

The registry identifies NCT01479127 as a completed Phase 2 study sponsored by AbbVie, with Abbott listed as prior sponsor. The study began in 2011-10 and had primary completion in 2012-07. Its official description calls it open-label, single-arm, baseline-controlled, and multicenter. Allocation is listed as not applicable, masking as none, and the model as single group. Enrollment was 8.

The listed treatment sequence began with a 28-day run-in period. During run-in, participants switched from prior anti-Parkinson’s medications to oral levodopa/carbidopa monotherapy, described as an oral 100 mg levodopa/10 mg carbidopa tablet optimized every 3rd hour during waking hours. The arm description then states that participants received ABT-SLV187, the intestinal gel, but the treatment-duration description is incomplete in the registry record. The registry also lists an infusion pump, an NJ tube, and an adaptor as study devices.

The design does not assign participants randomly to concurrent treatment groups. Although safety results are listed for oral tablets and intestinal gel, those groups should not be treated as equivalent arms of a controlled comparison. The registry explicitly cautions that they are not a like-for-like control comparison. Participants’ exposure periods and sequence differ, and the record does not report a randomized allocation process or masking that could support a direct causal comparison.

The primary endpoint is a participant count for adverse events, serious adverse events, and adverse events leading to discontinuation during run-in, up to approximately 28 days. The registry defines a full safety sample for run-in based on receipt of at least one dose of oral study drug. Details of a statistical analysis plan, including planned treatment comparisons or model specifications, 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Full safety sample: participants who had at least one dose of oral levodopa-carbidopa study drug in the Run-in Period.

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.

Population: full safety sample

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period, measured over During the Run-in period (up to approximately 28 days).

The primary endpoint counts participants who experienced adverse events, serious adverse events, and adverse events leading to discontinuation during the run-in period, which was up to approximately 28 days. It is a safety measure based on whether participants experienced events, rather than a measure of how many total events occurred or how severe a participant’s symptoms were on a clinical rating scale. The registry defines an adverse event as an untoward medical occurrence that does not necessarily have a causal relationship with treatment.

A serious adverse event is defined by outcomes such as death, a life-threatening event, hospitalization or prolonged hospitalization, congenital anomaly, persistent or significant disability or incapacity, or another important medical event. Severity was rated as mild, moderate, or severe. The registry also identifies adverse events of special interest, including device-associated gastrointestinal disorders, cardiovascular fatalities, aspiration including aspiration pneumonia, peripheral polyneuropathy, possible symptoms of peripheral polyneuropathy, and clinically significant weight loss.

Counting affected participants is useful for describing how many people in the safety population had at least one event in a category. It is not the same as counting every event: one participant may experience more than one event, and a participant count alone does not describe event duration or the full clinical course. Nor does an event count establish that study treatment caused the event. The primary endpoint is therefore suited to safety description, while attribution and interpretation require additional context that the registry record does not report in full.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods should be interpreted in light of the study’s single-group, open-label design and its small enrollment. The registry describes participant counts for adverse events rather than a randomized contrast. The safety data are therefore primarily descriptive: they report how many participants were at risk and how many were affected in each listed group. A descriptive count communicates what was recorded in those groups; it does not by itself estimate a causal treatment effect.

What does a participant count represent?

For a binary safety outcome, each participant is classified according to whether the event category occurred. The resulting count is the number of participants with an event, not the number of separate episodes. This distinction matters because a participant can experience more than one event, while still contributing only once to a participant-level count for that category. The registry’s primary endpoint uses participant counts for adverse events, serious adverse events, and events leading to discontinuation during run-in.

The record distinguishes serious adverse events from other adverse events and defines seriousness by outcomes such as death, life-threatening events, hospitalization, and important medical events. Seriousness is not the same as intensity: severity was rated as mild, moderate, or severe, while seriousness is based on the event’s consequences or importance. The posted group counts do not provide a full event-by-event account, so they cannot describe duration, recurrence, or the relationship between event severity and seriousness.

Why does the design limit comparison?

Random allocation can help make concurrent treatment groups comparable on average, while masking can reduce some forms of assessment bias. This study is listed as nonrandomized and unmasked, and the registry describes it as single-group and baseline-controlled. The oral tablets and intestinal gel appear in sequence rather than as randomized, concurrent controls. Consequently, the event counts cannot establish that any difference between groups was caused by the treatment received. Changes over time, differences in exposure, and other participant or study factors may also contribute.

Open-label status can also matter for event ascertainment. Participants and investigators know which treatment is being used, which may influence whether symptoms are reported, assessed, or categorized. This is a general methodological concern, not evidence that reporting was biased in this study. The registry does not report procedures that would quantify or eliminate such effects.

What can confidence intervals and tests add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the method used. A hypothesis test evaluates how compatible observed data are with a specified null hypothesis, also under assumptions. Neither can resolve a design limitation such as the absence of randomization. The registry information does not report confidence intervals, hypothesis tests, or an adjusted comparative analysis for the adverse-event counts. Statistical significance should therefore not be inferred from the counts.

With small groups, each participant’s experience can have a substantial influence on the observed summary. That makes estimates imprecise and limits the ability to detect uncommon events. The registry enrollment is 8, and the listed safety groups include 8 participants for oral tablets and 6 for intestinal gel. These counts describe the recorded safety groups; they do not establish that every outcome was available for every participant or that all participants had the same duration of exposure. Further details are not reported in the registry record.

How should planning calculations be read?

General sample-size planning translates a target effect, a significance level, allocation assumptions, and a statistical model into an illustrative amount of information needed for a future study. The planning assumptions associated with this analysis use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is stated as a fraction of the observed effect. For time-to-event outcomes, the planning quantity is total events using the Schoenfeld approach; for other outcomes, it is participants per arm.

Those calculations are planning illustrations, not the design justification reported by the investigators and not observed power for this completed study. The registry record does not report the trial’s own sample-size justification. Moreover, the two-arm equal-allocation assumption does not describe the actual single-group, nonrandomized sequence. Any future-study illustration should be understood as conditional on its stated assumptions, not as proof that the present study had a particular probability of detecting an effect.

Over-dispersion is a general issue for count outcomes when variation exceeds what a simple model assumes. Accounting for it can widen uncertainty or change estimated standard errors. The primary endpoint is expressed as participants with an event, rather than as an event-rate model, and the registry does not report an over-dispersion adjustment. It would therefore be inappropriate to claim that such an adjustment was used.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 24 outcome measures and 32 analyses. The secondary outcomes cover several domains, including motor states, diary assessments, UPDRS ratings, PDQ-39 scores, staging, daily activities, and global clinical impressions. When many outcomes are assessed, the chance of observing an apparently notable result by chance can increase if results are interpreted as separate confirmatory tests. General approaches to multiplicity include adjusting significance thresholds or identifying a prespecified hierarchy of outcomes. The registry record does not report whether multiplicity was addressed, which outcomes were treated as confirmatory, or how analyses were prioritized.

Missing-data handling is also not reported in the registry record. It does not describe the amount or pattern of missing outcome data, whether participants with missing assessments were excluded, or whether imputation or another method was used. Without these details, the potential effect of missing observations on the secondary outcomes cannot be assessed.

The run-in safety population is defined as participants who had at least one dose of oral levodopa-carbidopa study drug during run-in. That definition identifies who is included in the stated safety population, but it does not by itself explain analysis populations for later treatment outcomes. The registry record does not report a full set of analysis-population definitions or how deviations from the planned treatment sequence were handled.

These gaps affect how completely results can be evaluated. They do not establish that a particular method was or was not used; they mean the method is not reported in the registry record. In a small study with numerous listed outcomes, outcome selection, missingness, and analysis-population rules are important context for judging the stability and interpretability of any result.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: delusion (16.7%), hallucination, auditory (16.7%), somatic hallucination (16.7%).

The posted safety counts list 0 serious adverse events among 8 participants at risk in the oral levodopa-carbidopa tablet group and 1 among 6 participants at risk in the levodopa-carbidopa intestinal gel group. The other adverse event counts are 7 among 8 participants for tablets and 4 among 6 participants for intestinal gel. These are participant counts in the registry’s listed groups, not a randomized comparison.

The serious-event terms listed are Delusion, Hallucination, auditory, and Somatic hallucination, each reported as 16.7%. The registry record does not provide enough detail to determine whether the terms refer to distinct participants, how the denominator for each term was defined, or whether investigators considered the events related to treatment. An adverse event, by definition, does not necessarily have a causal relationship with treatment. Investigator assessments of probable or possible relationship are described, but the corresponding counts are not reported.

The groups represent different points in a treatment sequence, and the registry cautions against treating them as like-for-like controls. The counts describe events recorded in this study; they do not establish comparative risk or explain the cause of an event. A separate count for adverse events leading to discontinuation is not reported in the registry record.

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

The results can support a limited descriptive statement: adverse events were recorded in the listed oral-tablet and intestinal-gel groups, and the registry reports the number of participants at risk and affected in each category. The record lists 0 serious adverse events among 8 participants at risk in the oral tablet group and 1 among 6 in the intestinal gel group. It also reports other adverse events in 7 of 8 and 4 of 6 participants, respectively. These observations describe this study’s recorded groups.

They do not establish that the intestinal gel caused a serious adverse event, that oral tablets prevented serious events, or that one treatment is safer than the other. There was no randomized comparator, masking was absent, and the registry warns that the groups are not a like-for-like comparison. The treatment sequence, different exposure periods, and small group sizes restrict causal and comparative interpretation. An event recorded during treatment is not automatically caused by that treatment.

The counts also do not establish the frequency of uncommon events in a broader population. A small study may not observe events that occur infrequently, and observed counts can be sensitive to individual cases. The record does not report confidence intervals for these safety estimates or a formal comparison that would quantify uncertainty in a treatment contrast.

Nor do the safety figures answer the study’s efficacy questions. The registry lists secondary clinical outcomes, including motor ratings and patient-reported measures, but their numerical results are not reported in the registry record. The appropriate conclusion is not that the intervention works or does not work. Rather, the registry describes a small exploratory study and selected safety counts, while leaving important details about efficacy results and analysis methods unreported.

In general, a clinical trial’s interpretation depends on its design, outcome definitions, analysis methods, and completeness of reporting, in addition to the observed numbers. Here, the results are most informative as a record of events in the study groups, not as a basis for a definitive treatment comparison or a prediction for an individual patient.

13. Why This Trial Matters Statistically

This study illustrates why the design behind a safety count matters as much as the count itself. The registry reports event counts for oral levodopa-carbidopa tablets and levodopa-carbidopa intestinal gel, but describes a single-group, baseline-controlled sequence rather than randomized concurrent groups. The registry’s caution that the groups are not a like-for-like control comparison is central to interpretation. A numerical contrast is not automatically a treatment effect.

The study also shows the distinction between event presence and event burden. A participant-level count indicates whether participants experienced an event category, but does not summarize every event, its duration, or its severity. Seriousness is defined by consequences and clinical importance, while severity ratings use mild, moderate, or severe categories. Those concepts should not be conflated when reading safety data.

Small safety groups can identify events that occurred during a study, but they provide limited information about uncommon harms and about the precision of a comparative estimate. The registry lists 8 enrolled participants and 6 at risk in the intestinal-gel safety group. The counts are therefore best read as study-specific observations, not stable estimates of risk in a larger population.

Finally, a broad set of planned outcomes does not guarantee that all outcome results or analysis decisions are available in the registry record. Here, 24 outcome measures and 32 analyses are listed, while multiplicity procedures, missing-data methods, and detailed analysis populations are not reported in the registry record. This makes transparent reporting of prespecification and analysis choices especially important when interpreting exploratory clinical studies.

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 study’s enrollment was 8, and the posted safety groups are small. Such groups provide limited precision and may not capture uncommon events. The registry record does not provide confidence intervals for the safety counts, so their statistical uncertainty cannot be quantified from the reported information.

The design is open-label and single-group, with no randomized comparator. Oral levodopa-carbidopa appears during run-in and intestinal gel follows in the treatment sequence. The registry explicitly states that these groups are not a like-for-like control comparison. Differences in event counts cannot be assigned to treatment without accounting for the sequence and other possible differences.

The primary endpoint refers to adverse events, serious adverse events, and events leading to discontinuation during run-in, up to approximately 28 days. However, the safety results listed for oral tablets and intestinal gel do not, in the information, separately give the run-in count for each primary endpoint component or a discontinuation count. The scope and timing of all reported adverse-event counts are not fully detailed in the registry record.

The registry lists secondary efficacy and clinical measures, but their numerical results are not reported in the registry record. Detailed statistical methods, including any multiplicity strategy, missing-data approach, and analysis-population rules beyond the run-in safety population definition, are also not reported. The treatment-duration description is incomplete. Together, these reporting limits prevent a full assessment of outcome estimates, precision, and analysis choices.

Finally, the listed serious-event terms each carry a reported 16.7%, but the summarized record does not clarify whether terms refer to distinct participants or provide full event-level context. The event listing alone cannot establish attribution or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Safety, Tolerability, Pharmacokinetics, and Efficacy of ABT-SLV187 in Subjects With Advanced Parkinson's Disease — NCT01479127.
• Registry record last updated 2016-04-21; status last verified 2016-03.
• Results first posted 2016-03-15.
• 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

NCT01479127 is a completed Phase 2, open-label, single-group, baseline-controlled study of ABT-SLV187 in advanced Parkinson’s disease. The registry lists enrollment of 8, start in 2011-10, primary completion in 2012-07, and AbbVie as sponsor, with Abbott listed as prior sponsor. The study explored safety, tolerability, pharmacokinetics, and efficacy, including issues related to the naso-jejunum infusion system.

The primary endpoint counts participants with adverse events, serious adverse events, and events leading to discontinuation during run-in, up to approximately 28 days. Posted safety counts include 0 serious adverse events among 8 participants at risk in the oral tablet group and 1 among 6 in the intestinal-gel group. The registry cautions that these are not like-for-like control groups. Numerical results for the listed secondary outcomes, detailed statistical methods, missing-data procedures, and multiplicity handling are not reported in the registry record.