PROSEEK: A Phase 2 Study In Early Parkinson's Disease Patients Evaluating The Safety And Efficacy Of Abl Tyrosine Kinase Inhibition Using K0706: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PROSEEK: A Phase 2 Study In Early Parkinson's Disease Patients Evaluating The Safety And Efficacy Of Abl Tyrosine Kinase Inhibition Using K0706 (NCT03655236), a randomized phase 2 study. The primary outcome is Change From Baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score..

2. Clinical Question

The primary endpoint concerns motor examination scores. The registry describes Part III as an 18-item measure with a score range of 0-132; it notes that 32 and below is mild and 59 and above is severe. The endpoint is a change score, so the comparison focuses on the difference in average change over the stated period, rather than on an isolated Week 40 score.

The posted arm summaries report mean changes of 1.5 for low-dose K0706, 1.0 for high-dose K0706, and -1.0 for placebo. The unadjusted mean differences versus placebo are 2.5 for low dose and 2.0 for high dose. These summaries describe the observed data; they do not by themselves establish a treatment effect. Interpretation also depends on uncertainty, analysis methods, missing-data handling, and whether the comparisons account for multiple endpoints or doses.

3. Trial Design

PROSEEK is listed as a Phase 2, randomized, double-blind, placebo-controlled study with a parallel design and quadruple masking. The registry lists 513 participants enrolled. The listed study dates are 2019-02-18 for study start and 2024-04-08 for primary completion. Its current status is terminated.

The study had two parts. Part 1 assessed efficacy, safety, and tolerability of two K0706 doses compared with placebo in participants with early Parkinson's disease who were not receiving dopaminergic therapy. Part 2 was an optional long-term extension for participants who completed Week 40 of Part 1. The primary endpoint was measured at Week 40, while the registry also lists outcomes extending into Part 2.

The primary endpoint summaries are reported for the efficacy analysis set. Arm sizes in those summaries are 164 for low-dose K0706, 162 for high-dose K0706, and 161 for placebo. These arm counts align with the registry's overall enrollment, but the record does not describe the relationship between all enrolled participants and each analysis population in further detail.

Randomization and masking are design features intended to support fair comparisons and limit bias. General: random assignment can help balance known and unknown participant characteristics across groups, while masking can reduce the influence of expectations on treatment delivery, participant reporting, and assessment. The registry does not report the randomization method, allocation concealment details, or which parties are included in its quadruple-masking description.

The record does not report why the study was terminated, the original target enrollment, the protocol's sample-size justification, or the trial's planned statistical analysis. It also does not report a detailed account of the optional extension's eligibility and analysis procedures. These omissions limit conclusions about the reasons for the study's design choices and how the posted results relate to the original plan.

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.

Subject Disposition in Part 1 Period

Reasons for not completing this period:

Subject Disposition in Part 2 Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy analysis set

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 Change From Baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score., measured over Week 40.

The primary endpoint is change from baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III total score. Part III is the motor examination component. The registry describes it as containing 18 items, with a score range of 0-132, and gives severity context of 32 and below as mild and 59 and above as severe.

A change score represents how the measured score moved over the specified period. Comparing average change between a randomized treatment group and placebo can describe whether the groups' observed motor examination scores changed differently during Part 1. The scale provides a structured way to record motor examination findings, and a total score condenses multiple items into one endpoint for comparison.

General: continuous outcomes such as scores are commonly summarized by a mean and standard deviation. The mean describes the group's average change, while the standard deviation describes how dispersed individual scores are around that average. Neither statistic alone shows the full range of individual experiences.

The posted values are mean changes, not final scores, and the registry identifies the population as the efficacy analysis set. The record does not provide the scale's measurement properties, a threshold for a clinically important change, or additional details about the examination and scoring procedures. Therefore, the numerical contrast can be described statistically, but the record alone does not establish what size of change would be meaningful to participants or clinicians.

7. Results Posted in the Registry

• K0706, Low Dose: mean 1.50 versus -1.00 on control; difference 2.50 (95% CI 0.66 to 4.34), standardized effect d = 0.30; z-test p = 0.008.
• K0706, High Dose: mean 1.00 versus -1.00 on control; difference 2.00 (95% CI 0.29 to 3.71), standardized effect d = 0.25; z-test p = 0.022.

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.

To Determine if K0706 Delays the Initiation of Symptomatic Medications in Participants

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • K0706, Low Dose: 90.9% (149/164) versus 89.4% (144/161) on control; risk difference 1.4 percentage points (95% CI -5.1 to 7.9), risk ratio 1.02 (0.95–1.09); unadjusted two-proportion z-test p = 0.669.
  • K0706, High Dose: 79.6% (129/162) versus 89.4% (144/161) on control; risk difference -9.8 percentage points (95% CI -17.6 to -2.0), risk ratio 0.89 (0.81–0.98); unadjusted two-proportion z-test p = 0.015.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between K0706, Low Dose and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for K0706, High Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in Health Related Quality of Life as Measured by the European Quality of Life Questionnaire 5 Level Version

• 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 deviations.
• Result:
  • K0706, Low Dose: mean -0.04 versus -0.01 on control; difference -0.03 (95% CI -0.05 to -0.00), standardized effect d = -0.26; z-test p = 0.021.
  • K0706, High Dose: mean -0.05 versus -0.01 on control; difference -0.04 (95% CI -0.07 to -0.01), standardized effect d = -0.28; z-test p = 0.011.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for K0706, Low Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for K0706, High Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in Clinician Global Impression Severity

• 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 deviations.
• Result:
  • K0706, Low Dose: mean 0.20 versus 0.20 on control; difference 0.00 (95% CI -0.17 to 0.17), standardized effect d = 0.00; z-test p = 1.000.
  • K0706, High Dose: mean 0.00 versus 0.20 on control; difference -0.20 (95% CI -0.38 to -0.02), standardized effect d = -0.24; z-test p = 0.030.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between K0706, Low Dose and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for K0706, High Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes covering combined MDS-UPDRS Parts II and III change, initiation of symptomatic medication, health-related quality of life, clinician global impression of severity, autonomic symptoms, and serum K0706 concentration. Posted results are available for some of these outcomes, including comparisons for the medication-initiation measure, quality-of-life score, and clinician global impression. Other listed secondary outcomes do not have posted results in the record.

Across the reported outcomes, the numerical pattern is not uniform. Some unadjusted comparisons have intervals that exclude zero, while others do not. This range of findings is a reason to interpret secondary outcomes as a collection of supportive or exploratory observations rather than as a single consistent confirmation of the primary result. The secondary outcomes also measure different concepts, so their estimates are not direct replications of the motor examination endpoint.

Secondary outcomes can add context: a trial may measure function, quality of life, treatment initiation, or other domains alongside its primary measure. However, each additional test creates another opportunity for a result to appear unusual by chance. The registry does not report a multiplicity procedure or a prespecified hierarchy for these secondary tests. Their p-values are unadjusted, so they carry less evidential weight than results interpreted under a clearly defined testing strategy.

Some secondary results are participant counts, while others are continuous scores. These outcome types require different summaries and interpretations. The registry's descriptions identify the relevant timeframe, but it does not provide a complete analysis plan or detailed context for all measures. Therefore, the overall secondary pattern can be described as mixed and incomplete, but should not be used to claim that the primary finding is confirmed or contradicted.

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

• Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score.
• To Determine if K0706 Delays the Initiation of Symptomatic Medications in Participants
• Change in Health Related Quality of Life as Measured by the European Quality of Life Questionnaire 5 Level Version
• Change in Clinician Global Impression Severity
• Change in the Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire
• Serum Concentration Level of K0706

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous, and the registry says it is summarized as a mean with standard deviation. The posted means describe the average change in each group, while the standard deviations describe the spread of participant changes within each group. A mean difference compares two group averages. For the primary comparisons, the reported contrast is K0706 minus placebo.

What does a confidence interval express?

General: a confidence interval gives a range of estimates compatible with the observed data under the statistical method used. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. It is not a range containing every participant's outcome, and it does not represent the probability that a particular treatment effect is inside the interval.

The primary confidence intervals are reported as 0.662 to 4.338 for low-dose K0706 versus placebo and 0.285 to 3.715 for high-dose K0706 versus placebo. They express uncertainty around the calculated unadjusted mean differences. Their interpretation depends on the calculation method and assumptions; the registry does not report a full inferential analysis plan for these results.

What does a p-value add?

General: a p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the statistical model were correct. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of a difference. The posted unadjusted p-values for the primary comparisons are 0.008 and 0.022. The registry record lists no reported analyses for the primary outcome, so these should be distinguished from a sponsor-reported model-based analysis.

The word unadjusted is important. Each dose is compared with placebo, and the registry also lists multiple secondary outcomes. When multiple statistical tests are considered, the chance of at least one apparently unusual result can increase. General: a testing plan may address this through a prespecified hierarchy, adjustment, or other approach. Whether any such procedure was used for the trial is not reported in the registry record.

Why does variation matter?

General: the standard deviation measures the spread of participant-level values around the group mean. A mean difference is estimated less precisely when participant outcomes are more variable, all else being equal. The reported primary standard deviations are 8.77 for low dose, 7.58 for high dose, and 8.13 for placebo. These values help describe the observed spread but do not reveal the shape of the outcome distributions or whether model assumptions were checked.

The registry's posted comparison details include pooled standard deviations and standardized effect estimates. General: a pooled standard deviation combines the within-group variability for a two-group comparison, and a standardized effect expresses a mean difference relative to a measure of that variability. These can help put a continuous contrast on a scale less dependent on the original scoring units. They do not replace the original-unit mean difference or its confidence interval.

What is and is not reported about the analysis?

The primary endpoint is identified for the efficacy analysis set, and the arm-level summaries include the number of participants summarized in each group. The registry does not report the model specification, covariates, assumptions about missing outcomes, imputation procedures, sensitivity analyses, or whether baseline values were incorporated in an adjusted model. It also does not report whether the primary test was prespecified as one-sided or two-sided, although the sample-size illustration is explicitly described as two-sided.

The comparison values are unadjusted recalculations from posted summary statistics. They are useful for understanding the reported arm summaries, but they are not a substitute for a complete analysis based on participant-level data and the planned statistical model. The registry record lists zero reported analyses for the primary outcome. The record does not explain why analysis-level results are absent.

General: a randomized comparison can support an estimate of the difference between assigned groups when follow-up and analysis preserve the randomized comparison. Departures from assigned treatment, missing outcome measurements, or analysis exclusions can affect interpretation. The registry gives an efficacy analysis set but does not explain its inclusion criteria or how it was formed, so the extent to which the posted summaries represent all randomized participants cannot be fully assessed from the record.

11. Confidence Intervals and Precision

The primary mean-difference estimates are accompanied by confidence intervals. For low-dose K0706 versus placebo, the estimate is 2.5 with a 95% confidence interval from 0.662 to 4.338. For high-dose K0706 versus placebo, the estimate is 2.0 with a 95% confidence interval from 0.285 to 3.715. Both intervals are entirely above zero, which indicates that zero is not among the values covered by these unadjusted intervals under their calculation method.

General: a confidence interval communicates precision by showing a range of plausible effect estimates under a statistical procedure. It is not an interval for individual participant changes, and its width does not account automatically for design issues, missing data, or multiple testing. The intervals describe the recalculated unadjusted comparisons, rather than a reported adjusted sponsor analysis.

The arm-level standard deviations are 8.77, 7.58, and 8.13 for low-dose K0706, high-dose K0706, and placebo, respectively. These values indicate that participant changes varied around the group means. The registry does not provide the underlying distributions, so the degree of skewness, outliers, or other distributional features cannot be assessed from these summaries.

Precision is also distinct from clinical importance. The record does not report a threshold for a meaningful change on MDS-UPDRS Part III, so the intervals cannot be judged against such a threshold using the registry information alone. In addition, the record does not report how missing data were handled or whether the displayed comparisons reflect all randomized participants. Those uncertainties are separate from the numerical width of the intervals.

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 illustration translates an observed comparison into planning quantities under stated assumptions. For this continuous endpoint, the figures are participants per arm, not total events. The illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers effects equal to 100%, 75%, and 50% of the observed effect.

The 80% power column gives the number of participants per arm that the illustration estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions. The 90% power column gives the corresponding number per arm for a 90% chance. Greater power requires more participants when the other assumptions remain the same. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants.

These figures are illustrations based on the observed effect, not the trial's original design calculations. The protocol's own sample-size assumptions and justification are not reported in the registry record. The results are not observed power: they do not measure the probability that the completed trial detected an effect, and they cannot compensate for uncertainty in the observed effect estimate.

Planning based on an observed effect can be especially sensitive to the size of that estimate. General: observed effects from a study may be imprecise, and a planning exercise that treats them as fixed can understate or overstate the enrollment needed for future work. The values should therefore be read as assumption-dependent illustrations rather than recommendations or evidence about how the original study was designed.

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 = 2.500; pooled standard deviation σ = 8.459.
2. n = 2 × (1.96 + 0.842)² × 8.459² / 2.500² = 179.7, rounded up to 180 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 <- 2.5                      # observed difference in means
sigma <- 8.45902648666897                     # 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(3655236)
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 = 180 (80% power), 241 (90% power)
 75% of observed effect: n per arm = 320 (80% power), 428 (90% power)
 50% of observed effect: n per arm = 719 (80% power), 963 (90% power)
power.t.test: 180.7 
Simulated power at n = 180 per arm: 0.799 (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. Multiplicity, Missing Data and Analysis Populations

The record lists one primary endpoint, two K0706 dose groups, and multiple secondary outcomes. That structure creates multiple possible comparisons. The posted primary and secondary comparison p-values are unadjusted. The record does not report whether the study used a hierarchy, family-wise error control, a false-discovery approach, or another strategy to account for multiple testing.

General: when many hypotheses are tested, interpreting each p-value as if it were the only test can overstate the strength of evidence. A prespecified approach can define which comparisons are confirmatory and how error rates are controlled. Without that information, the posted unadjusted p-values are descriptive of individual contrasts and do not establish that a broader set of claims has met a multiplicity-controlled criterion.

The record does not report how missing primary outcome measurements were handled. It does not describe imputation, a likelihood-based approach, sensitivity analyses, or assumptions about why data might be missing. This matters because analysis of incomplete outcomes can depend on whether missingness is related to observed or unobserved outcomes.

The primary population is named as the efficacy analysis set, but its membership criteria are not reported. The registry does not state whether the analysis followed intention-to-treat principles, how treatment discontinuations or protocol deviations were handled, or whether participants with missing measurements were excluded. Arm counts in the posted outcome summaries are available, but they do not alone resolve these analysis-population questions.

The record also lists no reported analyses for the primary endpoint and no reported analyses for the listed secondary outcome with participant counts. Consequently, the posted summaries and unadjusted recalculations do not supply the missing details of the prespecified inferential plan. The original analysis plan, multiplicity strategy, and missing-data methods are not reported in the registry record.

15. 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: hyperglycaemia (1.8%), pneumonia (1.4%), coronary heart disease (1.4%), pneumonitis (1.4%), parkinson's disease (1.2%).

Safety counts are reported separately for Part 1 and Part 2. In Part 1, serious adverse events affected 14 of 171 participants in the low-dose group, 7 of 173 in the high-dose group, and 5 of 167 in the placebo group. The corresponding counts with other adverse events were 131, 150, and 124. Deaths reported for these groups were 1, 0, and 0, respectively.

For Part 2, the registry lists serious adverse events affecting 3 of 72 participants in the low-dose group and 11 of 117 in the high-dose group. Other adverse events affected 21 of 72 and 85 of 117, respectively. The placebo Part 2 group has zero participants at risk in the posted safety record, with zero events reported. These groups reflect the optional extension rather than a continuing randomized placebo comparison.

General: adverse-event counts describe how many participants were recorded as affected, not the severity, duration, or causal relationship of each event. The registry lists the most frequent serious-event terms with percentages, but does not provide enough detail to infer that a treatment caused an event. Exposure duration and the event-collection and coding methods are not reported in the registry record.

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

The posted primary summaries describe average MDS-UPDRS Part III changes over Part 1 and unadjusted differences between each K0706 dose group and placebo. They show positive mean-difference estimates for both dose comparisons, with confidence intervals that do not include zero under the reported unadjusted calculations. This is a description of the posted data, not a clinical recommendation or proof of a treatment effect.

Statistical evidence and clinical importance are different questions. The registry does not state a threshold for a meaningful change on the motor examination scale. It also does not provide participant-level outcome distributions or enough information about the analysis population and missing data to establish how broadly the group averages represent all randomized participants.

The unadjusted comparisons do not establish that multiplicity was controlled across dose groups and outcomes. The record does not report the planned statistical analysis or sponsor-reported primary analyses. Therefore, the comparisons should be viewed with the limits of summary-statistic recalculation in mind, rather than treated as a complete confirmatory analysis.

The trial's terminated status is relevant context, but the reason for termination is not reported in the registry record. It cannot be inferred from that status alone whether the study ended early, whether termination was related to efficacy or safety, or how it affected follow-up. The posted safety counts likewise do not establish causation or allow a complete comparison of risk without additional context about exposure and event ascertainment.

In short, the record contains useful group summaries and calculated uncertainty for the primary endpoint, as well as selected secondary and safety information. It does not supply all the protocol, analysis, missing-data, and clinical-interpretation details needed to turn these numbers into a definitive account of the study's overall evidence.

17. Why This Trial Matters Statistically

This study illustrates the difference between a registry outcome summary and a full statistical report. The primary endpoint is clearly identified, and arm-level means, standard deviations, comparison estimates, confidence intervals, and unadjusted p-values permit a reader to understand the observed contrasts. At the same time, the record lists no reported analyses for the primary endpoint, leaving important details of the planned analysis unknown.

It also illustrates why uncertainty and multiplicity matter together. Confidence intervals describe precision for individual unadjusted comparisons, but they do not account automatically for the presence of two dose comparisons and several secondary outcomes. Without a reported testing strategy, individual p-values should not be taken as a complete assessment of the evidence across the study.

The study includes an optional extension, making it important to distinguish the randomized Part 1 placebo comparison from later Part 2 safety summaries. The Part 2 placebo group has no participants at risk in the posted safety information, so extension data do not provide the same three-group comparison as Part 1.

Finally, the registry status is terminated, but its reason is not reported. That missing context limits interpretation of study conduct and completion. The case demonstrates how statistical interpretation depends not only on outcome estimates, but also on transparent reporting of design assumptions, analysis populations, missing-data methods, and the prespecified plan for interpreting multiple outcomes.

18. 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 registry record does not explain why the study was terminated. Without that context, the status cannot be linked to the primary results, safety findings, recruitment, or operational considerations. Nor does the record state whether termination changed follow-up or the planned analyses.

The original sample-size rationale is not reported. The available planning illustration uses observed effects and stated assumptions, which does not explain the enrollment target or power calculations used when the trial was designed. The record also does not provide a protocol-level analysis plan, including the planned model, covariate adjustment, or multiplicity strategy.

Although the primary endpoint is assigned to an efficacy analysis set, the registry does not define that set or say how missing measurements, treatment discontinuations, or protocol deviations were handled. The arm-level sample sizes alone cannot answer those questions. There are no reported primary analyses in the record, so the posted recalculations from summary statistics may not reflect the sponsor's planned inferential method.

The registry provides selected secondary outcomes, but not results for every listed measure. The secondary comparisons that are posted are unadjusted, and the record does not report a testing hierarchy. This makes it difficult to assess the broader pattern as a prespecified family of hypotheses.

Safety counts are divided between Part 1 and the optional extension, and the extension lacks a placebo group in the posted record. Detailed exposure time, event attribution, and adverse-event collection methods are not reported. These limitations restrict direct safety comparisons and causal interpretation.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: PROSEEK: A Phase 2 Study In Early Parkinson's Disease Patients Evaluating The Safety And Efficacy Of Abl Tyrosine Kinase Inhibition Using K0706 — NCT03655236.
• Registry record last updated 2025-07-25; status last verified 2025-07.
• Results first posted 2025-07-25.
• 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.

22. Record Summary

NCT03655236 is a randomized, double-blind, placebo-controlled Phase 2 parallel study of K0706 in early Parkinson's disease. The registry lists quadruple masking, 513 enrolled participants, study start on 2019-02-18, primary completion on 2024-04-08, and a terminated status.

The primary endpoint was change from baseline to Week 40 in MDS-UPDRS Part III total score. Posted means and unadjusted comparisons show positive mean differences versus placebo for both K0706 dose groups. The registry record does not report primary analyses or the trial's original statistical plan, including multiplicity and missing-data methods. The reason for termination is not reported in the registry record.