A Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety and Efficacy of PCN-101 in TRD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety and Efficacy of PCN-101 in TRD (NCT05414422), a randomized phase 2 study. The primary outcome is Montgomery Asberg Depression Rating Scale (MADRS) 24 Hours.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, parallel-group, placebo-controlled study of PCN-101 in treatment-resistant depression. The registry lists three arms: PCN-101 30 mg, PCN-101 60 mg, and placebo. The allocation field identifies the study as randomized. The brief summary describes the study as double-blind, while the registry masking field records triple masking. These descriptions are not identical; which roles were masked is not reported in the registry record.

The study description includes screening for up to 2 weeks, from Day -15 to Day -2; an in-clinic treatment period from Day -1 to Day 2, with blinded treatment on Day 1; and follow-up 7 and 14 days after infusion, on Days 8 and 15. The primary outcome was assessed 24 hours after infusion began. The registry reports 10 outcome measures and nine secondary outcomes posted. It lists a total enrollment of 102, whereas the brief summary describes a plan for 93 participants, with 31 in each of three arms. The record does not explain this difference.

The listed study start was 2022-02-01, and primary completion was 2022-11-10. The study status is completed. The sponsor is Perception Neuroscience. Further details about randomization procedures, concealment, treatment administration, or site-level conduct are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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 Montgomery Asberg Depression Rating Scale (MADRS) 24 Hours, measured over 24 hours.

The primary endpoint is change from baseline to 24 hours after the start of infusion in the Montgomery Asberg Depression Rating Scale (MADRS). The registry describes the reported outcome as a least-squares mean, with standard error as the measure of dispersion. The MADRS overall score ranges from 0 to 60, and higher scores indicate more severe depression. Thus, a negative change represents a lower score at follow-up than at baseline, while the clinical interpretation depends on the scale’s meaning and the study’s comparison between groups.

A standardized symptom scale allows investigators to describe change using the same scoring framework across participants and arms. Comparing changes between randomized groups can help distinguish the pattern observed after study treatment from changes also seen in the placebo arm over the same period. The endpoint’s 24-hour timing focuses on an early post-infusion measurement; it does not capture longer-term outcomes on its own.

The posted primary results give arm-level means and standard errors. The record does not report the endpoint’s analysis model, its covariates, or further details about the assessment procedures. Therefore, the least-squares mean label should be read as the reported summary, without assuming a particular adjustment or model specification.

7. Results Posted in the Registry

• PCN-101 30 mg: mean -13.70 versus -13.70 on control; difference 0.00 (95% CI -4.86 to 4.86), standardized effect d = 0.00; z-test p = 1.000.
• PCN-101 60 mg: mean -15.30 versus -13.70 on control; difference -1.60 (95% CI -6.38 to 3.18), standardized effect d = -0.16; z-test p = 0.512.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is presented as a least-squares mean change for each arm, with a standard error. A mean summarizes the central value of a continuous outcome across participants. In general, a least-squares mean is a model-based group estimate; its precise interpretation depends on the model and any adjustment variables. The model details and covariates are not reported in the registry record, so the estimates should be described using the registry’s label without inferring how they were adjusted.

What does the standard error describe?

In general, a standard error describes the sampling uncertainty of an estimated mean. It is not the same as the spread of individual participant scores: a standard error concerns uncertainty in the group estimate, while a standard deviation describes variation among observations. The primary results report standard errors of 1.75, 1.69, and 1.76 for the 30 mg, 60 mg, and placebo arms, respectively. These values provide context for the uncertainty of each arm’s estimated mean, but they are not a complete substitute for a confidence interval on a between-arm difference.

How should the between-arm estimates be read?

The reported comparison is a mean difference between each PCN-101 arm and placebo. A difference of 0 indicates equal arm means at the reported precision; a negative difference indicates a lower change estimate in the PCN-101 arm relative to placebo under the comparison’s stated direction. The recalculated unadjusted estimate for 30 mg was 0.0, and for 60 mg it was -1.6. The accompanying intervals quantify uncertainty around those estimates. They are recalculations from posted summary statistics, not sponsor-reported adjusted model results.

The recalculations use an approximate pooled standard deviation, as marked in the posted comparison information. In general, pooling combines information about variability across the two groups to estimate a common spread for an unadjusted comparison. This approach is a simplifying assumption; it may not reflect an adjusted model or other features of the original analysis. The registry does not report enough detail to reconstruct the sponsor’s primary model. The unadjusted p-values are 1.0 for the 30 mg comparison and 0.512 for the 60 mg comparison. A p-value measures how compatible the observed data are with a specified null hypothesis under the calculation’s assumptions; it is not the probability that the null hypothesis is true, nor does it measure clinical importance.

What do the confidence intervals add?

In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. The 30 mg comparison interval runs from -4.865 to 4.865; the 60 mg comparison interval runs from -6.382 to 3.182. Both include zero, so the estimates are not sharply separated from no mean difference under these unadjusted calculations. The intervals also include values on both sides of zero, indicating that the posted summaries do not determine the direction of the underlying contrast with high precision.

What do the planning illustrations mean?

The planning illustrations are not observed power and are not the trial’s design justification. They use the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They show hypothetical participants per arm for 80% and 90% power under assumptions that the effect to detect is 100%, 75%, or 50% of the observed effect. In general, planning for a smaller effect requires a larger sample to achieve a selected power target, all else held constant. The illustrations do not show that the completed trial had a particular power, and the trial’s sample-size justification is not reported in the registry record.

Over-dispersion is a general concern when outcome variability is greater than a model assumes; it can make standard errors and tests unreliable if not handled appropriately. The posted primary endpoint is continuous, and the registry does not report whether over-dispersion was assessed or relevant to the analysis. Similarly, the handling of missing observations, any interim analyses, and the sponsor’s detailed statistical plan are not reported in the registry record. No further modeling assumptions should be inferred from the posted summary results.

10. Confidence Intervals and Precision

The recalculated unadjusted confidence interval for the PCN-101 30 mg comparison is -4.865 to 4.865, around a mean difference of 0.0. For PCN-101 60 mg, the interval is -6.382 to 3.182, around a mean difference of -1.6. In general, a confidence interval shows the range of values reasonably compatible with the data under the method used. It is not a guarantee that the true value lies within that specific interval, and its width reflects both the observed variability and the amount of information available.

Both intervals include zero and extend to values on either side of it. The 60 mg interval is especially important to read as a range rather than as a single estimate: the point estimate is negative, but the interval also reaches positive values. The 30 mg point estimate is zero, while its interval allows nonzero differences in both directions. The posted results therefore leave uncertainty about the size and direction of the between-arm differences.

The primary endpoint standard errors were 1.75 for 30 mg, 1.69 for 60 mg, and 1.76 for placebo. These describe uncertainty in the arm means, not the range of individual responses. The recalculated comparison intervals use approximate unadjusted methods based on posted summary statistics; they are not a substitute for any sponsor-reported model-based interval. The registry does not report a sponsor confidence interval for the primary treatment comparisons in the information. Precision is also specific to the 24-hour endpoint and should not be carried over to other outcomes or time points.

11. Multiplicity, Missing Data and Analysis Populations

The record lists a primary MADRS endpoint and nine secondary outcomes as posted, including additional MADRS measures, depression and anxiety scales, clinical global ratings, and a quality-of-life measure. It reports zero analyses for the outcomes, so secondary comparison results are not available in the registry information. The registered outcome list alone does not establish which analyses were conducted or how they were interpreted.

Multiplicity arises in general when several outcomes, time points, doses, or comparisons are tested. Conducting multiple tests can increase the chance of at least one apparently unusual result. Researchers may address this through a prespecified testing hierarchy, adjustment procedure, or other strategy, but the approach for this trial is not reported in the registry record. The posted comparison p-values are unadjusted, and no multiplicity adjustment should be assumed.

The registry does not report whether interim analyses were conducted, how missing outcome data were handled, or which participants were included in the primary analysis population. It also does not identify whether the primary analysis followed an intention-to-treat principle or another population definition. These omissions limit assessment of the analysis plan and the relationship between the randomized groups and the reported outcome counts.

For the primary endpoint, the posted arm counts are 33, 35, and 33. The registry enrollment field reports 102 participants, while the study brief describes planned enrollment of 93. Safety denominators are 33, 35, and 34. These counts are distinct record entries; the registry does not explain their relationship or the reasons for any difference. Without participant flow and missing-data details, the completeness of the 24-hour outcome set cannot be determined from the registry record.

12. 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 non-serious adverse event terms

The safety record lists serious adverse events affecting 0 participants in each arm: among 33 at risk in the PCN-101 30 mg arm, 35 in the 60 mg arm, and 34 in the placebo arm. Deaths are listed as 0 in all three groups. No serious adverse event terms are listed in the record. These figures describe the counts recorded for the study groups and period represented by the safety entry; they do not establish that an event is impossible or that the groups have identical safety profiles.

The record also lists other adverse events affecting 11 participants in the 30 mg arm, 18 in the 60 mg arm, and 18 in the placebo arm. These are counts, not descriptions of event type, severity, timing, or causal relationship. The registry information does not provide those details. The safety denominators differ from the placebo primary-outcome count, so the outcome and safety counts should not be treated as interchangeable. With these data alone, the appropriate reading is a report of recorded counts, not a comparative safety conclusion.

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

The posted results describe short-term group averages on MADRS 24 hours after infusion began. Mean score changes were -13.7 for PCN-101 30 mg, -15.3 for PCN-101 60 mg, and -13.7 for placebo. The recalculated unadjusted contrasts were 0.0 for 30 mg versus placebo and -1.6 for 60 mg versus placebo, with both confidence intervals including zero. These estimates indicate what the registry summaries show at this time point; they do not, on their own, establish a definitive difference or equivalence between arms.

The results do not establish that an individual participant would have the same change as an arm average. They do not show how durable any changes were beyond the primary 24-hour assessment, and they do not answer the full set of secondary-outcome questions because those analyses are not listed. The study description includes follow-up on Days 8 and 15, but results for those follow-up assessments are not available in the registry information.

Nor do these results establish that there is no effect, or that a difference is clinically important. In general, the point estimate, interval, study design, outcome definition, and analysis methods all matter when interpreting a comparison. The confidence intervals allow values on both sides of zero, while the statistical model and missing-data approach are not reported in the registry record. The interpretation should therefore remain tied to the reported summaries and their uncertainty.

Finally, the results are specific to the trial’s enrolled study population, the three listed arms, and the stated endpoint timing. Detailed eligibility criteria, analysis-population definitions, and longer-term result estimates are not reported in the registry record. Generalization beyond the study conditions cannot be assessed from these primary results alone.

14. Why This Trial Matters Statistically

This trial is statistically informative because it includes two active-dose arms and a placebo arm, allowing each dose’s 24-hour change estimate to be compared with a concurrent control. The placebo arm also makes clear why within-group change is not the same as a treatment contrast: the placebo group’s mean MADRS change was -13.7, matching the 30 mg arm’s reported mean change. The comparison between randomized groups is more relevant to the treatment question than reading either arm’s change in isolation.

The primary results also illustrate the role of precision. A point estimate is only one summary of a comparison; its confidence interval shows the range of values compatible with the unadjusted calculation. Both recalculated intervals include zero and extend in both directions. This leaves uncertainty about the magnitude and direction of the group contrasts, even though the point estimates are available.

The record further highlights why trial summaries need to be read alongside design and analysis details. It reports a planned total of 93 in the brief description and an enrollment of 102 in the enrollment field, and it uses both double-blind wording and a triple-masking designation. The registry does not explain these differences. It also does not report the primary model, analysis population, missing-data handling, or multiplicity strategy. Those details affect how fully an independent reader can assess the estimates.

Finally, the record distinguishes outcome reporting from outcome listing: nine secondary outcomes are listed as posted, but no analyses are recorded. This limits the conclusions that can be drawn beyond the primary endpoint. These features make the study a useful example of interpreting arm means, unadjusted contrasts, and confidence intervals while keeping conclusions proportional to the available statistical detail.

15. 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 leaves several trial-specific uncertainties. The brief summary describes planned enrollment of 93, with 31 participants per arm, while the enrollment field reports 102. The primary outcome counts are 33, 35, and 33, and safety counts at risk are 33, 35, and 34. The record does not explain how these figures relate, or whether they reflect different analysis or safety populations.

The study is described as double-blind in the brief summary, but the masking field records triple masking. The roles covered by the masking designation and the reason for the different wording are not reported. The registry also does not provide the detailed randomization method, allocation concealment, primary statistical model, adjustment variables, analysis population, missing-data procedures, or multiplicity strategy. It is therefore not possible to verify those parts of the analysis from these registry entries.

The comparison estimates are recalculated, unadjusted results based on posted summary statistics and an approximate pooled standard deviation. The sponsor’s detailed analysis results are not reported in the registry information. The recalculated intervals and p-values should not be mistaken for adjusted sponsor estimates. Further, the record lists nine secondary outcomes but no analyses, limiting evaluation of results beyond the primary endpoint.

Finally, the primary outcome is measured at 24 hours after infusion began. Although the study description includes later follow-up, later outcome results are not reported in the information. The estimates therefore describe a particular time point and cannot characterize the trajectory of scores beyond it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety and Efficacy of PCN-101 in TRD — NCT05414422.
• Registry record last updated 2024-06-04; status last verified 2022-12.
• Results first posted 2024-06-04.
• 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.

19. Record Summary

The registry describes a completed Phase 2 randomized, parallel, placebo-controlled study of intravenous PCN-101 in treatment-resistant depression. The three arms were PCN-101 30 mg, PCN-101 60 mg, and placebo. The primary endpoint was MADRS change from baseline to 24 hours after the start of infusion.

Posted mean changes were -13.7, -15.3, and -13.7, respectively. Recalculated unadjusted mean differences versus placebo were 0.0 for 30 mg and -1.6 for 60 mg; both confidence intervals included zero. The registry lists nine secondary outcomes but no analyses. It reports no serious adverse events or deaths in the three arms. The record does not report the detailed primary model, analysis population, missing-data approach, or multiplicity plan.