Phase 3 Efficacy and Safety Study in Adults With ADHD Using CTx-1301.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 3 Efficacy and Safety Study in Adults With ADHD Using CTx-1301. (NCT05631626), a randomized phase 3 study. The primary outcome is The Primary Efficacy Analysis Will Analyze the Change in PERMP Scores From Baseline (Pre-dose) at Visit 8 to Hour 16 at Visit 8..

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group study conducted at a single center. Its stated purpose was to evaluate the efficacy and safety of CTx-1301 in adults with ADHD in a laboratory-classroom setting. The registry lists enrollment as 26 and the study status as completed.

The protocol description includes a dose-optimization phase before randomization. Participants started at 25mg on Day 0 and were titrated to an optimal dose; possible doses were 25mg, 37.5mg, or 50mg. The record says participants were expected to remain on their optimal dose for 2 sequential weeks before the randomized phase. It then describes randomization in a 1:1 ratio to the optimal dose or placebo in a 7-day double-blind phase. The posted primary results group the active treatment as CTx-1301 rather than reporting separate results for each dose.

The registry lists the study start as 2022-12-29 and primary completion as 2023-06-13. The posted primary endpoint is a PERMP-C score change at Visit 8, at hour 16. The record also lists two key secondary analyses: PERMP score changes at each time point during the laboratory environment at Visit 8, and change in Clinical Global Impression-Severity score from the pre-dose baseline at Visit 2 to Visit 8. Results for those secondary outcomes are not reported in the registry record.

The record does not report further details about site procedures, concealment implementation, adherence, or the rationale for the selected enrollment. Those details 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: The study included a screening period of up to 4 weeks, followed by a 5-week open-label dose optimization period, followed by a 1-week randomized, placebo-controlled, double-blind period.

Screening/Dose Optimization (9 Weeks)

Double-Blind Period (7 Days)

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 were titrated to their optimal dose during the dose-optimization phase. Each subject was expected to be on their optimal dose for 2 sequential weeks prior to the double-blind randomization phase. Subjects were randomized (1:1) to their optimal dose or placebo in the 7-day, double-blind, randomization phase. As a result, 26 subjects entered the dose optimization phase and 21 completed the dose optimization phase. Twenty one subjects entered and completed the double-blind phase.

6. Primary Endpoint

The registry lists the primary outcome as The Primary Efficacy Analysis Will Analyze the Change in PERMP Scores From Baseline (Pre-dose) at Visit 8 to Hour 16 at Visit 8., measured over Average of the change of the PERMP-C scores from baseline defined as pre-dose score at Visit 8 which was at end of 7-day double-blind period to PERMP-C scores at hour 16 at Visit 8..

The primary endpoint is change in PERMP-C score from the pre-dose score at Visit 8 to the score at hour 16 at Visit 8. PERMP-C is described as an objective, validated, skill-adjusted, 10-minute math test. It measures attention and accuracy by counting math problems answered correctly. Its scale ranges from a minimum score of 0 to a highest possible score of 400; higher scores indicate higher performance and less severe ADHD symptoms.

Using a performance task gives the trial a defined, measurable outcome under the laboratory-classroom conditions in which the study was conducted. The comparison concerns change from a pre-dose score, rather than only the score at the later assessment. In general, a change score expresses how an outcome differs from a participant's baseline measurement; it does not by itself describe every aspect of functioning outside the measurement setting.

The registry reports least-squares mean changes and 95% confidence intervals. These are model-based summaries as named in the record, but the model specification is not reported in the registry record. The posted endpoint is a score change at a particular visit and time point; it is not a direct measure of all ADHD symptoms or of outcomes beyond the laboratory-classroom assessment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: it is a score on a scale, and the registry identifies the reported parameter as a least-squares mean. The posted values are changes from baseline, not raw scores at hour 16. The record describes the baseline as the pre-dose PERMP-C score at Visit 8 and the later measurement as the score at hour 16 at that visit.

What does a least-squares mean represent?

In general, a least-squares mean is an estimated mean produced by a statistical model. It may account for terms included in that model, so it need not be identical to a simple arithmetic average. The registry record does not report the model formula, included covariates, assumptions, or estimation details. It is therefore not possible to say from the record which adjustments, if any, distinguish these estimates from unadjusted means.

How should the confidence intervals be read?

The reported 95% confidence intervals quantify uncertainty around each arm's least-squares mean change, conditional on the analysis method and its assumptions. In general, a confidence interval is not a probability statement that a particular fixed value lies within the calculated interval. It is a range generated by a method that, under repeated use and its assumptions, has a stated coverage property. These arm-specific intervals do not directly quantify the uncertainty around the difference between CTx-1301 and placebo. A direct comparison estimate and its interval would be needed to assess that contrast on the same scale.

Why do analysis details matter?

General statistical considerations include the choice of analysis population, handling of missing outcome values, and specification of the model. Each can affect the estimate or its uncertainty. For example, a model that accounts for baseline values or other factors may produce an adjusted estimate; the registry record does not say whether such terms were used. Missing-data methods matter because results can depend on how absent measurements are treated. The methods for missing data and the analysis populations are not reported in the registry record.

Randomization is a design feature intended to support a fair comparison by assigning participants to study groups by chance. Double blinding is intended to limit the influence of group knowledge on participants and study conduct. Those design labels do not replace a complete account of the analysis. The registry describes randomization and double blinding, but further implementation details are not reported in the registry record.

What can be inferred from the posted analysis?

The registry lists an arm-level least-squares mean change and confidence interval for each group. It does not report the treatment contrast, a test statistic, or a p-value for the primary endpoint. Without those comparative results, the arm-level estimates cannot be treated as a complete hypothesis test of CTx-1301 versus placebo. In general, comparing two estimates requires attention to their joint uncertainty, not just each estimate considered separately.

The registry also lists two key secondary analyses, but their results are not reported in the registry record. The record does not describe multiplicity procedures, interim analyses, or the statistical analysis plan. Consequently, the methods used to control interpretation across endpoints or analyses cannot be assessed from this record.

The registry's 95% confidence intervals and least-squares mean labels are useful descriptions of the posted estimates, but readers should avoid inferring unreported modeling choices. A detailed statistical analysis plan, full results, and information about missingness would be needed to evaluate those choices. In general, transparency about model specification and analysis populations helps readers understand what an estimate targets and how robust it may be to alternative reasonable methods.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two key secondary analyses in addition to the primary endpoint. One concerns PERMP score changes at each time point during the laboratory environment at Visit 8; the other concerns the change in CGI-S score from the pre-dose baseline at Visit 2 to Visit 8. Results for these secondary analyses are not reported in the registry record.

When a study evaluates multiple endpoints or multiple time points, the chance of at least one apparently notable finding can increase if each is assessed independently. In general, multiplicity procedures can address that issue by defining how results across tests are interpreted. The registry record does not report a multiplicity adjustment or other method for handling multiple comparisons. It also does not report interim analyses or the statistical analysis plan, so those procedures cannot be assessed.

The record does not describe missing outcome data, reasons for missingness, or methods used to handle missing values. It does not define the analysis populations used for the primary estimate. These details matter in general because estimates may depend on which participants and measurements are included and on how unavailable measurements are treated. The posted arm-level participant counts do not, on their own, explain exclusions or missing outcomes.

These are reporting limitations, not evidence that a particular method was or was not used. The applicable details are not reported in the registry record.

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 non-serious adverse event terms

The registry reports zero serious adverse events in the dose-optimization phase, with 26 participants at risk. In the double-blind treatment phase, it reports zero serious adverse events among 11 participants at risk in the CTx-1301 group and zero among 10 at risk in the placebo group. The record also reports zero deaths in each listed group.

These figures describe the serious-event counts recorded for the stated groups and phases. A count of zero means no serious adverse events were recorded in those groups in the registry results; it does not establish that the risk of serious events is absent. The size of the study and the duration of observation affect how much can be learned about uncommon events. The registry record does not report further detail about event definitions, follow-up after treatment, or event-level narratives.

The record separately lists other, non-serious adverse events affecting 25 participants during dose optimization, 1 in the CTx-1301 double-blind phase, and 3 in the placebo phase. These are distinct categories from serious adverse events and should not be combined with the serious-event counts. The registry record does not provide further detail about the nature or severity of those other events in the information.

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

The posted results show positive mean changes in PERMP-C score in both the CTx-1301 and placebo arms at the specified assessment. The confidence intervals indicate uncertainty around each arm's estimated mean change. Because the registry does not report a direct between-arm estimate or a primary comparison p-value, the arm-level results alone do not establish the statistical evidence for a treatment contrast.

In general, a result on a laboratory performance measure speaks most directly to that measured task, in the conditions and at the time points studied. PERMP-C assesses correct answers on a timed math test and is described as measuring attention and accuracy. It is not a complete measure of every symptom, daily activity, or longer-term outcome relevant to adults with ADHD. The registry record does not report outcomes beyond those listed.

The results also do not establish a conclusion about each dose separately. Although the study included 25mg, 37.5mg, and 50mg options during dose optimization, the posted primary estimates combine CTx-1301 as one active-treatment group. No dose-specific primary results are reported in the registry record.

Safety results are similarly limited to the recorded counts and group descriptions. Zero serious adverse events in the listed groups should not be interpreted as proof that serious events cannot occur. The registry record does not report enough detail to characterize uncommon risks or compare safety precisely.

Overall, the record supports a cautious description of the measured score changes and their reported precision. It does not provide the complete comparative analysis, methods detail, or outcome coverage needed for broader conclusions.

13. Why This Trial Matters Statistically

This study illustrates why arm-level estimates and treatment comparisons are not interchangeable. The registry reports a least-squares mean change and a 95% confidence interval for each arm, but does not report a direct estimate of the difference between arms. In general, a reader needs the comparative estimate and its uncertainty to evaluate the contrast that randomization was designed to study.

It also highlights the importance of reporting the analysis behind a model-based estimate. Least-squares means can be useful summaries, but interpretation depends on the model specification, analysis population, and missing-data approach. Those details are not reported in the registry record. Without them, the estimates can be described but their modeling assumptions cannot be fully evaluated.

The laboratory-classroom endpoint is a defined performance measure, with a stated range and interpretation. That specificity supports a focused statistical question, while also making the scope of the result important: the endpoint represents performance on the described task at the specified assessment, not every possible clinical outcome.

Finally, the record pairs efficacy results with safety counts but provides limited detail about event characterization and analysis procedures. This makes clear that statistical interpretation relies on more than a point estimate: precision, the comparison of interest, endpoint scope, and reporting completeness all shape what can responsibly be concluded.

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 registry reports arm-specific primary estimates but does not report a between-arm treatment estimate, confidence interval for that contrast, test statistic, or p-value. That limits direct statistical interpretation of the randomized comparison. The record also does not explain the model used to produce the least-squares means, including whether baseline or other variables were included.

The primary results combine CTx-1301 across dose levels. Although dose options of 25mg, 37.5mg, and 50mg are described, dose-specific primary outcome estimates are not reported in the registry record. The record describes an optimal-dose process, but further detail about dose assignment and participant-level exposure is not reported.

The study is described as single-center and conducted in a laboratory-classroom setting. The extent to which results apply to other settings or outcomes cannot be determined from the posted primary endpoint alone. The registry record does not report details about participant characteristics beyond the adult ADHD population description, or about the analysis population used for the primary results.

Methods for missing data, multiplicity, and interim analyses are not reported in the registry record. The record also does not report the statistical analysis plan or further detail about the serious adverse events beyond the counts. These limitations constrain assessment of robustness, precision of the comparison, and safety characterization.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 3 Efficacy and Safety Study in Adults With ADHD Using CTx-1301. — NCT05631626.
• Registry record last updated 2026-07-02; status last verified 2026-06.
• Results first posted 2026-07-02.
• 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

NCT05631626 is a completed phase 3 randomized, double-blind, parallel-group, placebo-controlled study of CTx-1301 (dexmethylphenidate) in adults with ADHD. It was conducted at a single center in a laboratory-classroom setting. The registry lists enrollment as 26, a study start of 2022-12-29, and primary completion on 2023-06-13.

The primary endpoint was change in PERMP-C score from pre-dose at Visit 8 to hour 16 at Visit 8. The posted least-squares mean changes were 24.94 for CTx-1301 and 13.09 for placebo, each with a 95% confidence interval. A direct between-arm estimate and its inferential results are not reported in the registry record. The registry lists two key secondary analyses, whose results are not reported in the registry record.

Serious adverse event counts were zero in the listed dose-optimization and double-blind groups. Further analysis details, including model specification, missing-data methods, and analysis populations, are not reported in the registry record.