Study Comparing Continuous Subcutaneous Infusion Of ABBV-951 With Oral Carbidopa/Levodopa Tablets For Treatment Of Motor Fluctuations In Adult Participants With Advanced Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Comparing Continuous Subcutaneous Infusion Of ABBV-951 With Oral Carbidopa/Levodopa Tablets For Treatment Of Motor Fluctuations In Adult Participants With Advanced Parkinson's Disease (NCT04380142), a randomized phase 3 study. The primary outcome is Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Troublesome Dyskinesia.

2. Clinical Question

The registry describes a randomized, quadruple-masked, parallel-group phase 3 study. Its stated aim was to compare efficacy, safety, and tolerability in advanced Parkinson’s disease. The primary endpoint focuses on a daily symptom experience recorded in a participant diary, rather than on a laboratory measure. The registry record reports the endpoint definition, assessment period, and analysis result, but the trial’s original sample-size justification and other protocol-level details are not reported in the registry record.

3. Trial Design

The study was randomized, quadruple-masked, and parallel-group, with an active control. The registry identifies the phase as phase 3 and the condition as Parkinson’s disease. Enrollment was 174. The study began on 2020-10-19, primary completion was 2021-09-29, and its status is completed.

Both groups first passed through an open-label levodopa/carbidopa stabilization period. During the subsequent 12-week double-blind treatment period, one group received ABBV-951 by continuous subcutaneous infusion and oral placebo for levodopa/carbidopa. The other received oral levodopa/carbidopa and a continuous subcutaneous placebo infusion. This double-dummy arrangement matched the routes and forms of treatment across groups. The registry describes the masking as quadruple; the identities of all roles covered by that masking are not reported in the registry record.

The brief summary describes approximately 130 planned participants and approximately 80 sites across the world, while the registry enrollment is 174. The study included regular hospital or clinic visits, with medical assessments, blood tests, side-effect checks, and questionnaires described in the summary. The primary endpoint was assessed from baseline through week 12, using diary data collected over three consecutive days and normalized to a 16-hour waking day.

The primary analysis concerns participants with a baseline and week 12 assessment, while the endpoint description defines the broader Full Analysis Set. The registry reports outcome-specific analysis counts, which need not match overall enrollment. The exact allocation sequence, site list, and original design assumptions 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: Enrolled participants entered an open-label oral Levodopa/Carbidopa (LD/CD) Stabilization Period of 14 to 21 days, at the end of which, eligible participants were randomized 1:1 to 12 weeks of treatment with either: 24-hour/day continuous subcutaneous infusion (CSCI) of ABBV-951 + oral placebo capsules for LD/CD immediate-release (IR) or 24-hour/day CSCI of placebo solution for ABBV-951 + encapsulated LD/CD IR tablets in a 12-week Double-Blind Treatment Period.

LD/CD Stabilization Period

Reasons for not completing this period:

Double-Blind Treatment Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with a baseline and Week 12 assessment.

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: Safety Analysis Set: All participants who received any dose of study drug during the Double-Blind Treatment Period.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Troublesome Dyskinesia, measured over Baseline (Week 0) up to Week 12 of the double-blind treatment period.

The primary endpoint is change from baseline to week 12 in average daily normalized “On” time without troublesome dyskinesia, measured in hours. “On” time is defined as periods of good motor symptom control. The endpoint adds normalized “On” time without dyskinesia to normalized “On” time with non-troublesome dyskinesia. The diary measure is normalized to a 16-hour waking day and averaged over three consecutive days. Baseline is the average from the three diary days before randomization.

This endpoint is used to capture how much of the waking day participants spend in a state of good motor symptom control without troublesome dyskinesia. It therefore focuses on a daily experience relevant to motor fluctuations, rather than only a single examination at a clinic visit. The registry reports least-squares means and standard errors for each group, and a between-group contrast from a mixed model repeated-measures analysis.

General statistical context: a change score describes the difference between a participant’s follow-up measurement and their baseline measurement. Comparing the groups’ changes aims to distinguish the pattern over time between assigned treatments from the level observed at baseline. A least-squares mean is a model-based estimate; its interpretation depends on the fitted model and analysis population. The registry record does not report the full model specification or all assumptions behind that model.

7. Results Posted in the Registry

• ABBV-951 + Placebo for LD/CD: mean 2.72 versus 0.97 on control; difference 1.75 (95% CI 0.34 to 3.16), standardized effect d = 0.46; z-test p = 0.015.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "Off" Time (Hours)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • ABBV-951 + Placebo for LD/CD: mean -2.75 versus -0.96 on control; difference -1.79 (95% CI -3.16 to -0.42), standardized effect d = -0.49; z-test p = 0.011.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for ABBV-951 + Placebo for LD/CD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline to Week 12 of the Double-Blind Treatment Period in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • ABBV-951 + Placebo for LD/CD: mean -2.65 versus -1.06 on control; difference -1.59 (95% CI -3.82 to 0.64), standardized effect d = -0.27; z-test p = 0.163.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ABBV-951 + Placebo for LD/CD and the control. The interval gives the range of effects that remain compatible with the data.

Early Morning "Off" Status (Morning Akinesia) at Week 12 of the Double-Blind Treatment Period

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • ABBV-951 + Placebo for LD/CD: 17.0% (8/47) versus 63.3% (38/60) on control; risk difference -46.3 percentage points (95% CI -62.6 to -30.1), risk ratio 0.27 (0.14–0.52); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for ABBV-951 + Placebo for LD/CD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The available secondary results show a pattern that broadly aligns with the primary contrast for some measures, but the evidence is not uniform across outcomes. The reported “Off” time comparison and early-morning “Off” status comparison have estimates and confidence intervals that support a between-group difference under their reported analyses. The MDS-UPDRS Part II result is less conclusive: its confidence interval includes zero. This range of findings cautions against treating all secondary outcomes as though they provide the same strength of evidence.

These outcomes address related but distinct aspects of Parkinson’s disease experience and function. Their relationship to the primary endpoint is therefore supportive context, not a direct replication of the same measure. Results for several other listed secondary measures are not reported in the registry record, so the available findings do not give a complete account of every planned or listed secondary outcome.

The reported secondary analyses use different outcome scales and, for early-morning “Off” status, a different statistical model. Their numerical estimates cannot be compared as if they shared a common unit. The simple recalculations are unadjusted, and the registry does not report an overall multiplicity procedure for secondary testing. When many outcomes are examined, the chance of at least one apparently notable result can rise unless the analysis plan addresses that issue. Consequently, unadjusted secondary p-values carry less weight than a result interpreted within a clearly reported testing hierarchy. The hierarchy and adjustment details are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "Off" Time (Hours)
• Change From Baseline to Week 12 of the Double-Blind Treatment Period in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Score
• Early Morning "Off" Status (Morning Akinesia) at Week 12 of the Double-Blind Treatment Period
• Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Dyskinesia (Hours)
• Change From Baseline to Week 12 of the Double-Blind Treatment Period in Parkinson's Disease Sleep Scale-2 (PDSS-2) Total Score
• Change From Baseline to Week 12 of the Double-Blind Treatment Period in Quality of Life Assessed by Parkinson's Disease Questionnaire 39 Item (PDQ-39) Summary Index Score
• Change From Baseline to Week 12 of the Double-Blind Treatment Period in Quality of Life Assessed by the EuroQol 5-Dimension Questionnaire (EQ-5D-5L) Summary Index
• Change From Baseline to Week 12 of the Double-Blind Treatment Period in Median Bradykinesia Score (BK50) as Assessed by the Parkinson's KinetiGraph/Personal KinetiGraph (PKG) Wearable Device

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports the primary comparison as a mixed model repeated-measures analysis. It gives a least-squares mean of the difference, a 95% confidence interval, a p-value, and a superiority analysis label. The result is a model-based comparison of change over time between the assigned groups, rather than a simple comparison of the two endpoint means alone.

What does the mean difference represent?

For this continuous endpoint, the contrast is expressed in hours. A positive value means the estimated change in “On” time without troublesome dyskinesia was greater in the ABBV-951 group than in the oral levodopa/carbidopa group, under the reported contrast direction. The registry’s reported estimate is 1.75. The analysis estimates an average group contrast; it does not imply that every participant experienced that change.

The group estimates are least-squares means, which are model-based averages. General statistical context: a repeated-measures model can use outcome observations collected at multiple time points and account for their association within participants. The registry record does not report the model’s covariance structure, included covariates, missing-data assumptions, or the detailed handling of observations after treatment discontinuation. Those details should not be inferred from the method label alone.

How should the p-value be read?

The reported primary p-value is 0.008. General statistical context: a p-value measures how incompatible the observed data are with a specified null model, given the analysis assumptions. It is not the probability that the null hypothesis is true, nor does it quantify the probability that the result will be replicated. A p-value also does not communicate the effect’s size or practical importance; those require attention to the estimate, its units, and its uncertainty.

The registry labels the primary analysis as superiority. This indicates that the reported test addressed whether the groups differed in the favorable direction under the analysis framework. The superiority label alone does not supply the full hypothesis-testing plan, including any hierarchy across endpoints or multiplicity adjustment. Those elements are not reported in the registry record.

What does the confidence interval add?

The sponsor’s 95% confidence interval for the primary difference is 0.46 to 3.05 hours. General statistical context: a confidence interval describes the range of values compatible with the data and the analysis procedure at the stated confidence level. Its width reflects precision: narrower intervals indicate more precise estimates than wider intervals, all else equal. It does not mean there is a 95% probability that this particular interval contains the fixed true effect.

The separate recalculation is an unadjusted calculation from posted summary statistics. It estimates the primary mean difference as 1.75 hours, with an interval of 0.336 to 3.164 and p = 0.015. It is not the sponsor’s repeated-measures model and should not replace that analysis. Because the registry reports no discrepancy flag, the sponsor’s result remains the principal result to interpret; the recalculation offers a simple comparison based on the available group summaries.

Why can the recalculation differ?

The posted group means and standard errors do not contain every element that may inform a repeated-measures model. A simple unadjusted calculation cannot reproduce adjustments, covariance handling, or other features of the sponsor’s fitted analysis. The recalculation also uses an approximate standard deviation derived from the reported standard errors. General statistical context: model-based and summary-statistic approaches can yield different standard errors and confidence limits because they use information and assumptions differently. Such differences should be described, not resolved by choosing whichever result is more favorable.

What is the role of the analysis population?

The primary endpoint description defines the Full Analysis Set as randomized participants who received any dose during the double-blind period and had baseline and at least one post-baseline observation for at least one efficacy assessment. The primary outcome additionally identifies participants with baseline and week 12 assessments. The outcome-specific counts are 62 in the oral levodopa/carbidopa group and 47 in the ABBV-951 group. These analysis counts are distinct from overall enrollment and from the safety-group denominators. The registry record does not provide a complete participant flow explanation for the difference between those counts.

General statistical context: restricting a particular endpoint analysis to participants with the required measurements can affect how well the analyzed group represents all randomized participants. The consequences depend on why measurements are missing and how the model handles them. The registry record does not report enough detail to determine whether missingness could have influenced the estimate.

11. Confidence Intervals and Precision

The sponsor’s primary estimate is 1.75 hours, with a 95% confidence interval from 0.46 to 3.05 hours. The interval excludes zero, in the direction of a greater estimated change for ABBV-951. Its lower and upper limits still span a range of possible group differences, so the estimate should not be read as an exact effect applying to every participant.

General statistical context: confidence intervals communicate uncertainty around an estimate under the method used to calculate them. A 95% confidence procedure would cover the fixed target value in 95% of repeated applications under its assumptions. For an individual study, the interval is one calculated range, not a probability statement about where the fixed effect lies. The interval also does not account automatically for possible bias, missing data, measurement error, or unreported design choices.

The unadjusted recalculation gives a 95% confidence interval of 0.336 to 3.164 hours. It is somewhat wider than the sponsor’s model-based interval and is based on the posted group summaries rather than the full repeated-measures analysis. This distinction matters: both intervals describe uncertainty under their own calculation methods, and the sponsor’s analysis is the primary reported trial analysis.

The confidence interval for the secondary MDS-UPDRS Part II difference runs from -3.65 to 0.48, including zero. In contrast, the reported secondary intervals for “Off” time and early-morning “Off” status exclude their respective null values. These different intervals indicate varying precision and evidence across outcomes. They do not by themselves determine whether the measured differences are important to participants. The registry record does not report a minimal clinically important difference for the primary endpoint.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effects, not the original trial design. For continuous outcomes, they are participants per arm. The assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; each illustration detects the stated fraction of the observed effect. The time-to-event convention does not apply to these outcomes.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding per-arm count for a 90% chance. These are design calculations, not guarantees about a future study’s result. They are not observed power.

Rows for 100%, 75%, and 50% of the observed effect show how the planning count changes when the effect to detect is set at a smaller fraction of the observed estimate. Smaller effects need more participants to detect, all else equal, so the illustrative counts increase as the assumed effect becomes smaller. The figures are planning scenarios, not evidence that the observed effect is stable or that a particular future study would reproduce it.

The original study’s sample-size justification, target power, and design effect assumptions are not reported in the registry record. The trial enrollment was 174, but the primary endpoint analysis included 62 and 47 participants in the respective groups. Those observed analysis counts should not be confused with the per-arm planning figures.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 1.750; pooled standard deviation σ = 3.782.
2. n = 2 × (1.96 + 0.842)² × 3.782² / 1.750² = 73.3, rounded up to 74 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 1.75                      # observed difference in means
sigma <- 3.78154001166365                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4380142)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 74 (80% power), 99 (90% power)
 75% of observed effect: n per arm = 131 (80% power), 175 (90% power)
 50% of observed effect: n per arm = 294 (80% power), 393 (90% power)
power.t.test: 74.3 
Simulated power at n = 74 per arm: 0.793 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s primary analysis is the mixed model repeated-measures result: a least-squares mean difference of 1.75 hours, a 95% confidence interval of 0.46 to 3.05, and p = 0.008. This is the principal reported comparison for the primary endpoint. The estimate and interval are expressed in hours of change in normalized “On” time without troublesome dyskinesia.

The unadjusted recalculation from posted summary statistics also gives a mean difference of 1.75 hours, but its 95% confidence interval is 0.336 to 3.164 and its p-value is 0.015. The point estimate agrees, while the uncertainty and test result differ. This is expected to be possible because a calculation from group summaries does not reproduce the sponsor’s repeated-measures model and uses approximate variability derived from the reported standard errors.

The recalculation is a check on the posted summary values, not a replacement for the sponsor’s analysis. It does not have the model details or participant-level data needed to replicate that analysis. The registry record does not report every model specification, so the source of each difference cannot be isolated. In interpreting the trial, the sponsor’s own analysis takes precedence; the recalculation helps illustrate how the headline contrast relates to the posted group means and uncertainty.

15. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary endpoint and multiple secondary outcomes. It gives a primary analysis and selected secondary analyses, but the testing strategy across those outcomes is not reported in the registry record. In particular, any planned hierarchy, adjustment for multiple comparisons, or control of the overall type I error rate is not reported. The reported p-values should therefore be interpreted as belonging to their individual analyses unless the registry documents a broader adjustment.

General statistical context: testing several outcomes creates multiple opportunities to observe a small p-value by chance, even when no true differences exist. Multiplicity procedures can manage that issue, but their interpretation depends on which outcomes are included and the planned order or method of testing. Without those details, secondary results are best viewed as supportive or exploratory rather than as independent confirmatory claims. This does not alter the numerical results; it affects how strongly they can be interpreted together.

The primary endpoint description identifies the Full Analysis Set and a requirement for baseline and week 12 observations for this result. It does not fully describe missing-data handling in the repeated-measures model. The registry record does not report the amount or reasons for missing primary outcome data, sensitivity analyses for missingness, or the assumptions used to handle unavailable observations. Missingness can matter if participants without measurements differ systematically from those with measurements.

The exact protocol-defined analysis populations, deviations from the planned analysis, and detailed imputation methods are not reported in the registry record. The reported outcome counts are informative about the analyzed groups, but do not by themselves explain all exclusions from the enrollment total. These gaps limit assessment of robustness, especially if missing outcome data or analysis choices were associated with treatment assignment or participant outcomes.

16. 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: covid-19 pneumonia (1.5%), cellulitis (1.5%), contusion (1.5%), fall (1.5%), nephrolithiasis (1.5%).

The adverse-event record separates the LD/CD stabilization period from the two double-blind treatment groups. During stabilization, 4 of 174 participants had a serious adverse event and 15 of 174 had another adverse event; there were no deaths. In the LD/CD plus placebo-for-ABBV-951 group, 4 of 67 had a serious adverse event, 18 of 67 had another adverse event, and 1 death was recorded. In the ABBV-951 plus placebo-for-LD/CD group, 6 of 74 had a serious adverse event, 51 of 74 had another adverse event, and no deaths were recorded.

These are event-group counts and denominators as recorded, not a comparative safety analysis adjusted for exposure or participant characteristics. The stabilization period is separate from the double-blind groups, so it should not be combined with them when reading treatment-period counts. The listed serious-event terms each have a reported frequency of 1.5%: COVID-19 pneumonia, cellulitis, contusion, fall, nephrolithiasis, and acute respiratory failure.

General statistical context: adverse-event counts describe what was recorded in the stated groups and periods; they do not alone establish whether an event was caused by treatment. The registry record does not provide exposure-adjusted rates or a detailed causal assessment for these events. These figures should be read as descriptive safety information, not as proof of comparative safety.

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

The primary result describes a between-group difference in change in daily normalized “On” time without troublesome dyskinesia over the 12-week double-blind treatment period. The sponsor’s reported model estimates a difference of 1.75 hours, with a 95% confidence interval of 0.46 to 3.05 hours. That interval indicates uncertainty around the estimated average contrast and is consistent with a positive difference under the reported model.

The result does not mean that every participant experienced a 1.75-hour change, nor does it describe the likely outcome for a specific individual. It is an average comparison among the participants included in the primary analysis. The registry reports a specific diary-based endpoint, population definition, and follow-up period; extrapolation beyond those conditions is not established by these results.

The statistical findings alone do not determine how important the difference is to participants. The registry record does not report a threshold for clinical importance, and a p-value does not answer that question. Nor does the primary result establish long-term effects, results in other populations, or the balance of benefits and harms beyond the recorded study period. The adverse-event counts provide descriptive information but do not by themselves establish causation or a complete comparative safety profile.

Secondary findings add context but vary in certainty, and several listed outcomes lack results in the registry record. Multiple outcome testing and missing-data details also affect how strongly those secondary results can be interpreted. The most precise account is therefore bounded: the posted primary analysis estimates a positive mean difference for the defined endpoint over the defined period, with the reported interval expressing statistical uncertainty. It is not a complete account of every outcome or a basis for medical advice.

18. Why This Trial Matters Statistically

This study is statistically notable because it compares two treatment strategies using a randomized, double-blind, double-dummy, active-controlled design. Matching an infusion and oral capsules across both groups helps maintain masking while comparing continuous subcutaneous ABBV-951 with oral levodopa/carbidopa. The outcome is also directly tied to the trial’s stated focus on motor fluctuations: diary-recorded time in a defined “On” state.

The primary result includes both a model-based estimate and enough posted summary data for a simple unadjusted recalculation. Comparing these results illustrates an important distinction in clinical-trial interpretation: a similar point estimate can coexist with different confidence limits and p-values when the analyses use different methods. The sponsor’s repeated-measures analysis remains the main reported result, while the recalculation is a limited check rather than a replication.

The registry also makes visible the difference between total enrollment and outcome-specific analysis counts. That distinction matters when evaluating how much information supports a particular estimate. Secondary outcomes add breadth, but the lack of reported multiplicity procedures and missing-data details limits how conclusively the results can be combined. Overall, the record offers a clear primary contrast while leaving important analytical details unreported, a useful reminder that interpreting a trial requires attention both to the estimate and to the design and reporting context.

19. 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 analysis includes 62 participants in the oral levodopa/carbidopa group and 47 in the ABBV-951 group, while total enrollment is 174. The registry defines the analysis population but does not provide a full participant flow account explaining the outcome-specific counts. This makes it difficult to assess from the record alone why participants were absent from the primary endpoint analysis.

The registry reports the mixed model repeated-measures method but not its detailed specification, including covariance structure, covariates, or missing-data assumptions. The amount and reasons for missing endpoint observations and sensitivity analyses are not reported in the registry record. These omissions limit independent assessment of how robust the estimate is to modeling choices and missing data.

The original sample-size justification and design assumptions are not reported in the registry record. The planning illustrations based on observed effects are not a substitute for the trial’s original design rationale. The registry also does not report a clear multiplicity strategy for the secondary outcomes. Several listed outcomes have no reported results, further limiting a complete reading of the planned outcome pattern.

The primary endpoint uses diary reports normalized to a 16-hour waking day and averaged over three consecutive days. The registry gives the measurement definition but not details on adherence, diary completion quality, or the clinical threshold for an important difference. The study’s double-blind treatment period lasted 12 weeks; longer-term outcomes are not established by this endpoint. These limitations do not erase the reported estimate, but they constrain conclusions about its precision, clinical relevance, and generalizability.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study Comparing Continuous Subcutaneous Infusion Of ABBV-951 With Oral Carbidopa/Levodopa Tablets For Treatment Of Motor Fluctuations In Adult Participants With Advanced Parkinson's Disease — NCT04380142.
• Registry record last updated 2022-11-18; status last verified 2022-10.
• Results first posted 2022-11-18.
• 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.

23. Record Summary

NCT04380142 is a completed randomized phase 3, quadruple-masked, parallel-group active-controlled study of ABBV-951 versus oral levodopa/carbidopa in adults with advanced Parkinson’s disease. Enrollment was 174. After an open-label stabilization period, participants received 12 weeks of double-blind treatment with either continuous subcutaneous ABBV-951 and oral placebo, or oral levodopa/carbidopa and placebo infusion.

The primary endpoint was change from baseline to week 12 in average daily normalized “On” time without troublesome dyskinesia. The sponsor’s mixed model repeated-measures analysis reported a difference of 1.75 hours, a 95% confidence interval of 0.46 to 3.05, and p = 0.008. The registry also reports selected secondary results and descriptive adverse-event counts. Details of the original sample-size justification, multiplicity strategy, and missing-data methods are not reported in the registry record.