A Study of Clenbuterol (CST-103) Co-administered With Nadolol (CST-107) in Subjects With Neurodegenerative Disorders: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Clenbuterol (CST-103) Co-administered With Nadolol (CST-107) in Subjects With Neurodegenerative Disorders (NCT04739423), a randomized phase 2 study. The primary outcome is Change From Baseline in Negative Emotional Bias in the Facial Expression Recognition Task (FERT).

2. Clinical Question

3. Trial Design

This was a Phase II, randomized, placebo-controlled crossover study of clenbuterol (CST-103) co-administered with nadolol (CST-107) in subjects with neurodegenerative disorders. The registry record lists enrollment as 41 and status as completed. The recorded study start was 2021-06-28, and primary completion was 2022-07-04.

The two treatment sequences began with different assignments. In the CST-103/CST-107-to-placebo sequence, participants were scheduled to receive daily active combination for 14 days, have no drug for a 14-day washout, and then receive matching placebos for 14 days. In the placebo-to-CST-103/CST-107 sequence, the order was reversed, with the same stated treatment and washout durations.

A crossover design assigns treatment periods sequentially rather than keeping each participant in a single treatment group throughout. In general, this structure can support within-participant comparisons because each participant experiences the assigned treatment conditions. It also makes the sequence and washout relevant to interpretation: results can depend on the timing of treatment, period effects, or effects persisting across periods. The registry record does not report how these issues were handled in the analysis.

The official title describes the study as double-blind, while the registry's masking classification is quadruple. The record does not explain this difference or specify which roles were masked. It describes the study as randomized and placebo-controlled but does not report the randomization procedure, allocation concealment details, or a statistical analysis plan.

The study included populations with mild cognitive impairment, Lewy body dementia, Parkinson's disease rapid eye movement sleep behavior disorder, and Parkinson's disease dementia. The primary endpoint description specifies that it applied to Cohort A only. The record does not report how the cohorts were defined or how participants were distributed across them.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) - The FAS included all randomized study subjects who had taken at least one dose of blinded study drug in this crossover study. In accordance with the protocol this outcome measure was only applicable for Cohort A. Data are presented by treatment for each patient population analyzed.

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: All subjects enrolled in study.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Negative Emotional Bias in the Facial Expression Recognition Task (FERT), measured over Days 7 and 14 of each Treatment Period (Two 14-day periods).

The primary endpoint was change from baseline in negative emotional bias in the Facial Expression Recognition Task (FERT), reported as percent change. The task briefly displays faces showing happiness, fear, anger, disgust, sadness, or surprise, and participants indicate the expression using a button press. The endpoint was measured on days 7 and 14 of each treatment period, and the record specifies least-squares means with standard errors. Its use was limited to Cohort A.

As a general measurement concept, a facial-expression task captures performance on a structured recognition task. An endpoint focused on negative emotional bias can describe how responses to emotional expressions are distributed, rather than serving as a direct measure of everyday functioning or disease progression. In this study, the task was used as a pharmacodynamic measure within a trial of central nervous system effects. That makes it a measure of a task response under study conditions; the registry record does not establish how a change on the task should be interpreted clinically.

The record does not report the numerical change from baseline by treatment, a treatment contrast, confidence intervals, or a p-value for this primary endpoint. It therefore does not establish the direction or precision of a treatment difference in the posted results. The use of least-squares means describes the planned summary measure, but details of the model used to produce them are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to treatment sequences using a chance-based process. In general, random assignment is intended to reduce systematic differences between groups at the start of a study. The registry record identifies the study as randomized but does not report the sequence-generation method, allocation concealment, or other implementation details. The label alone does not establish how those procedures were carried out.

A placebo-controlled design compares active treatment with a matching inactive comparator. Here the record describes matching placebos for both CST-103 and CST-107. In a crossover study, the assigned treatments are received in sequence, with a washout between treatment periods. The listed sequences use 14 days of treatment, a 14-day no-drug washout, and 14 days of the other condition. In general, crossover designs can make within-participant comparisons possible, but period effects, sequence effects, and carryover are important considerations. The registry record does not report the analysis methods for these design features.

The official title calls the study double-blind, while the registry masking classification says quadruple. Masking is intended, in general, to limit the influence of treatment knowledge on participant behavior, study conduct, or outcome assessment. The record does not identify the roles covered by its masking classification or explain the difference in wording, so the exact masking arrangements are not reported in the registry record.

What does a least-squares mean describe?

A least-squares mean is generally an estimate produced from a statistical model. Depending on the model, it can represent a treatment mean adjusted for other terms included in that model. It is not necessarily the same as the simple arithmetic average of observed values. The primary endpoint specifies least-squares means, but the model terms, estimation method, and handling of repeated observations are not reported in the registry record. The label therefore describes the intended summary, not enough detail to reproduce or evaluate its calculation.

How should a standard error be read?

In general, a standard error describes the sampling uncertainty associated with an estimate. It is not a description of the spread of individual participant measurements. A smaller standard error indicates a more precisely estimated mean under the analysis assumptions, whereas a larger one indicates less precision. The primary endpoint specifies standard errors, but no numerical values are reported in the registry record. A standard error alone would not fully convey uncertainty in a treatment contrast; a confidence interval around that contrast would also help readers assess its range of plausible values.

What does the endpoint measure?

The Facial Expression Recognition Task records responses to briefly presented faces showing six basic emotions. The endpoint is described as change from baseline in negative emotional bias and is expressed as percent change. In general, a task-based endpoint reflects performance under the conditions in which the task is administered. It should not automatically be treated as a measure of broader cognitive function, daily activity, or disease course. The record does not report additional validation or interpretation criteria for this endpoint.

How should uncertainty and statistical significance be assessed?

General statistical interpretation considers both the estimated effect and its uncertainty. A confidence interval can show a range of values compatible with the observed data under the model and its assumptions. A p-value, when reported, can quantify how unusual data at least as extreme as those observed would be under a specified null hypothesis. Neither substitutes for judging the magnitude and relevance of an estimate. The registry record does not report a confidence interval or p-value for the primary endpoint, nor does it describe the test used.

What analysis details are missing?

The record identifies a Full Analysis Set for the primary endpoint: randomized study subjects who took at least one dose of blinded study drug. It does not report the number included in that analysis, the amount or pattern of missing endpoint data, the approach to missing observations, or whether any sensitivity analyses were conducted. It also does not report model assumptions, a prespecified contrast, a multiplicity procedure, or whether interim analyses occurred. These omissions prevent a full assessment of the statistical methods from the registry record alone.

The record lists 6 outcome measures and 19 analyses. General multiplicity concerns arise when many outcomes, time points, or comparisons are examined, because the chance of at least one nominally unusual result can increase across a set of tests. Whether and how that issue was addressed is not reported in the registry record. The listed analysis count does not by itself reveal the testing strategy or justify a particular adjustment.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures and 19 analyses. The primary endpoint includes assessments on days 7 and 14 of each treatment period, and its description limits the measure to Cohort A. In general, considering multiple outcomes, time points, cohorts, or treatment comparisons can create multiplicity: the chance of obtaining at least one apparently notable result may rise when many statistical tests are considered. The record does not report whether a multiplicity adjustment, hierarchical testing plan, or other prespecified strategy was used.

The registry identifies the primary endpoint analysis population as the Full Analysis Set. This set included randomized study subjects who had taken at least one dose of blinded study drug. That definition does not indicate how many people contributed data to the endpoint or whether every member had measurements at every scheduled assessment. The number analyzed is not reported in the registry record.

Missing endpoint data, reasons for missingness, and the methods used to address missing observations are not reported in the registry record. In general, missing-data methods rely on assumptions about why observations are unavailable; different assumptions can affect estimates and uncertainty. The record also does not report sensitivity analyses that might show how conclusions change under alternative assumptions.

The statistical model, treatment contrast, and handling of period and sequence effects are not reported in the registry record. These details matter for a crossover analysis and are needed to understand how the estimates were obtained. The record does not report whether interim analyses occurred or provide a statistical analysis plan.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (33.3%), hypoglycaemic seizure (4.2%).

The registry lists serious adverse event counts separately by condition group and treatment. For PD, the placebo group had 0 serious adverse events among 25 at risk, and the active group had 1 among 24 at risk. For MCI, the placebo group had 0 among 12 at risk, and the active group had 0 among 13 at risk. For PDD and DLB, the placebo group had 1 among 3 at risk, and the active group had 0 among 2 at risk. The record lists 0 deaths in each group.

These are counts within the posted groupings, not estimates adjusted for exposure duration or differences between groups. Because the study used a crossover design, participants received treatment conditions in sequence; the registry record does not provide enough detail to interpret these group counts as independent parallel-group comparisons. It also does not report event timing or individual-level information.

The registry lists Anaemia at 33.3% and Hypoglycaemic seizure at 4.2% among the top serious adverse event terms. The record does not make clear the denominators or group-specific distribution for those percentages. Other adverse events affected 16 in PD placebo, 20 in PD active, 4 in MCI placebo, 7 in MCI active, 2 in PDD and DLB placebo, and 2 in PDD and DLB active.

These safety figures describe what was recorded; they do not establish that a treatment caused an event or allow a reliable comparison of risk. Sparse group counts and missing detail about timing, exposure, and event attribution limit interpretation.

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

The study design addresses a pharmacodynamic question: whether a task-based measure of negative emotional bias changed from baseline under clenbuterol co-administered with nadolol compared with matching placebo. Its randomized, placebo-controlled crossover structure and scheduled assessments provide a framework for comparing treatment periods. The primary endpoint applies only to Cohort A, so the stated question does not cover every listed population through that endpoint.

The registry record does not report numerical primary endpoint results. As a result, it does not show the estimated direction or size of the treatment difference, or how precisely that difference was estimated. No conclusion about whether the endpoint changed more under one condition, or whether any observed difference would be clinically meaningful, can be drawn from the posted primary results.

The endpoint measures performance on a facial-expression recognition task. In general, a change on a task measure is not automatically equivalent to a change in daily functioning, quality of life, or the course of a neurodegenerative disorder. The registry record does not report a threshold for clinically important change or evidence connecting this endpoint to those broader outcomes.

The safety listings provide counts of serious and other adverse events by the displayed condition and treatment groups, and list no deaths in those groups. They do not by themselves establish causality or support a definitive comparison of treatment safety. The small listed group counts in some categories, along with absent details on timing, attribution, and exposure, constrain what can be concluded.

More broadly, a completed trial record is not a substitute for reported outcome estimates and analysis details. The record does not report confidence intervals, p-values, model specifications, missing-data methods, or the approach to multiplicity for the primary endpoint. Those omissions prevent a complete assessment of the strength and robustness of the statistical evidence.

13. Why This Trial Matters Statistically

This trial illustrates why design and reporting details matter when assessing a clinical study. A crossover design exposes participants to treatment conditions in sequence, which can support within-participant comparisons in general. It also makes period, sequence, and carryover considerations relevant. Without the analysis model and related handling details, readers cannot determine how those features entered the primary comparison.

The study spans several neurodegenerative disorder populations, while the primary Facial Expression Recognition Task endpoint is specified for Cohort A only. That distinction matters: an endpoint result from a restricted cohort would not automatically describe outcomes in every population named in the record. The registry does not report cohort definitions or the primary endpoint estimates, limiting assessment of population-specific interpretation.

The record also distinguishes a task-based pharmacodynamic outcome from broader clinical outcomes. The endpoint captures responses to emotional faces under task conditions. General statistical interpretation requires attention to what a measure directly records, and not to assume that a task change establishes a change in daily function or disease progression.

Finally, the record shows why estimates and their uncertainty are essential. An endpoint name and analysis summary do not reveal the treatment contrast, its precision, or how missing data and multiple analyses were handled. The registry record's missing numerical primary results leave those questions unresolved. Reporting estimates alongside uncertainty and transparent analysis methods would allow readers to judge the evidence more fully.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting the primary endpoint is the absence of numerical results in the registry record. Treatment estimates, the contrast between conditions, standard errors, confidence intervals, and p-values are not reported. The statistical model and its assumptions are also not described, limiting evaluation of the stated least-squares mean analysis.

The primary endpoint applies only to Cohort A, but the record does not report how that cohort was defined or how many participants contributed endpoint data. Although the record states that data are presented by treatment for each patient population, the numerical primary endpoint findings are not reported. The scope of any primary comparison across populations therefore cannot be assessed.

The crossover design has features that require analytic consideration, including treatment period, sequence, and possible carryover. The record describes the treatment order and washout but does not report how these features were addressed statistically. Details about allocation, masking roles, and the discrepancy between the double-blind title and quadruple masking classification are also not reported.

The record does not describe missing endpoint data, reasons for missingness, missing-data methods, or sensitivity analyses. It lists 6 outcome measures and 19 analyses but does not report how multiplicity was addressed. The absence of these details limits assessment of robustness and the risk of selective emphasis among analyses.

Safety interpretation is constrained by the group-specific counts, sparse counts in some groups, and absent details about event timing, attribution, and exposure. The record does not provide information sufficient to establish that a particular treatment caused a listed event or to make a definitive comparative safety assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Clenbuterol (CST-103) Co-administered With Nadolol (CST-107) in Subjects With Neurodegenerative Disorders — NCT04739423.
• Registry record last updated 2024-12-02; status last verified 2024-10.
• Results first posted 2024-12-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT04739423 is a completed Phase II randomized, placebo-controlled crossover study of clenbuterol (CST-103) co-administered with nadolol (CST-107) in subjects with neurodegenerative disorders. The registry lists enrollment as 41, a study start of 2021-06-28, and primary completion on 2022-07-04.

Treatment sequences used active combination and matching placebo in opposite orders, with a 14-day washout between 14-day treatment periods. The primary endpoint was change from baseline in negative emotional bias on the Facial Expression Recognition Task, expressed as percent change and assessed on days 7 and 14 of each treatment period. It applied to Cohort A only.

The registry record does not report numerical results for the primary endpoint or the analysis details needed to evaluate its estimate and uncertainty. Serious and other adverse event counts are reported by displayed condition and treatment groups, with 0 deaths listed in each group.