Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1 (NCT03959189), a randomized phase 1 study. The primary outcome is Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo.

2. Clinical Question

The record describes safety and tolerability as the primary purpose. Its secondary purpose was to evaluate potential changes in excessive daytime sleepiness or hypersomnia and cognitive function relative to placebo. The listed measures include the Stanford Sleepiness Scale, patient and clinician global-improvement scales, a Psychomotor Vigilance Task, and a One-back Task. Those aims identify what the trial sought to assess; they do not establish that any difference was observed.

Because the same participants were intended to receive both treatments in different periods, the main comparison is conceptually within-participant rather than a simple comparison of unrelated groups. That structure can help account for stable differences between participants, but interpretation also depends on how treatment order, period effects, and possible carryover are handled. The registry record does not report those analysis details. The posted safety counts are organized by cohort and treatment period, so they should be read as period-specific observations rather than as a complete estimate of a treatment effect.

3. Trial Design

This was a completed Phase 1 randomized, double-blind, placebo-controlled crossover trial. The registry reports enrollment of 12 adults with DM1. Each participant was described as receiving ERX-963 and placebo on different days in randomized fashion, with a washout period between the periods. The record lists two sequences: ERX-963 followed by placebo, and placebo followed by ERX-963. It does not report how many participants entered each sequence.

The study included a 1 mg ERX-963 period in Cohort 1 and a 2 mg ERX-963 period in Cohort 2. Each cohort also had a placebo period. The posted risk sets differ by cohort: Cohort 1 lists 7 participants at risk in each period, while Cohort 2 lists 5 participants at risk in each period. These are the counts shown for the safety outcomes, not a basis for inferring the number assigned to each sequence or the reasons for any difference between enrollment and period-specific counts.

Masking is recorded as double. The registry does not specify which trial roles were masked or describe how masking was maintained. The official title characterizes the study as a dose-range-finding crossover trial of single-day administration. The registry lists the start date as 2019-06-17, primary completion as 2020-03-31, and status as completed.

The primary objective was safety and tolerability. The listed secondary outcomes concern sleepiness, global impressions of improvement, vigilance, and performance on a One-back Task. The registry record does not report the full protocol, the washout duration, sequence-specific enrollment, or details of treatment administration beyond the listed intervention periods. It also does not report the statistical analysis plan or a rationale for the enrollment target. These omissions limit how fully the planned design and its analysis can be reconstructed from the registry record alone.

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

Analysis population for the primary outcome, as defined in the registry: The safety population is defined as all participants who sign the study-specific informed consent documents and received at least 1 dose of ERX-963 or placebo.

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 Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo, measured over Adverse Events were collected from screening to the End of Study Visit, up to 57 days.

The primary endpoint concerns the incidence of adverse events, serious adverse events, and drug-related adverse events after a single dose of ERX-963 versus placebo. It is expressed as a count of participants, rather than as a continuous measure such as a laboratory value or symptom score. The registry defines an adverse event broadly as an unfavorable or unintended medical occurrence associated in time with study intervention, whether or not the event was judged related to the intervention. An event could include a symptom, disease, or abnormal laboratory finding.

The registry distinguishes treatment-emergent events from the broader collection period. Treatment-emergent adverse events were those that started between dosing and Study Day 2 within each period. The broader adverse-event collection ran from screening to the End of Study Visit, up to 57 days. Drug relationship was assessed by the investigator as related or unrelated for each event occurrence. The registry record does not provide separate posted counts for drug-related events.

General statistical context: safety endpoints are used to describe the types and frequency of events observed during exposure, and can help identify issues that merit further evaluation. Counts are especially important to interpret alongside the number of participants at risk in each period. In a crossover study, period-specific counts describe what was recorded during each treatment period; without participant-level event information and a stated comparison method, they do not by themselves quantify a paired treatment effect. The registry record provides counts but no confidence intervals or formal test for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: trial design determines what comparisons are meaningful, while the analysis method determines how the observed data are used to estimate those comparisons. The registry identifies a randomized, double-blind crossover design but does not report the statistical analysis plan. The discussion below explains general considerations relevant to this design and does not describe analyses as having been performed unless they are stated in the registry record.

What does a crossover design compare?

In a crossover trial, participants receive more than one treatment in separate periods. Each participant can therefore contribute observations under ERX-963 and placebo. General statistical context: a within-participant comparison can reduce the influence of characteristics that remain stable within a person, because the participant serves as their own comparator. This benefit depends on having suitable paired data and an analysis that respects the pairing. The posted counts are arranged by cohort and period, but the registry record does not report participant-level paired outcomes or a paired treatment estimate.

Treatment sequence and period can also matter. Symptoms, event likelihood, or other measurements may change over time regardless of treatment. A treatment received first may have different observed outcomes from the same treatment received later. In addition, an effect that persists after a period could influence a later period. General statistical context: these are period and carryover considerations in crossover studies. The registry describes randomized treatment order and a washout period, but the washout duration and the methods used to assess or account for period, order, and carryover are not reported in the registry record.

How should event counts be understood?

The primary outcome is a count of participants with adverse events, serious adverse events, and drug-related adverse events. The posted counts distinguish serious events from other adverse events and give the number at risk in each period. General statistical context: a participant count is not the same as a count of event episodes. One participant can have more than one event, and a participant can potentially contribute observations in more than one crossover period. The registry record does not provide event-level or participant-level detail that would show those patterns.

For the listed groups, serious adverse-event counts are 0; other adverse-event counts are 0, 1, 2, and 1 in the order of the Cohort 1 placebo, Cohort 1 1 mg ERX-963, Cohort 2 placebo, and Cohort 2 2 mg ERX-963 periods. The corresponding risk sets are 7, 7, 5, and 5. Those are descriptive results. The record does not report a treatment-effect estimate, confidence interval, or test of statistical significance for them.

General statistical context: a confidence interval is a range of values compatible with the data under a specified statistical model and procedure. It conveys uncertainty in an estimate; it is not a guarantee that the true value lies in that range. With sparse event counts, uncertainty can be substantial, and the choice of method matters. No confidence intervals are reported for the posted safety counts, so their precision cannot be assessed through that measure in the registry record.

Why does the analysis population matter?

The registry defines the safety population as all participants who signed the study-specific informed consent documents and received at least 1 dose of ERX-963 or placebo. This definition describes who is intended to be included in the safety population. It does not establish how many participants were analyzed, whether every eligible participant contributed to each period-specific count, or how incomplete observations were handled. The analyzed population and participant flow are not reported in the registry record.

General statistical context: the population used for a safety analysis can differ from the population used for an efficacy analysis. Safety summaries commonly depend on actual treatment exposure, while other analyses may use different eligibility or adherence rules. The registry record does not report a separate analysis population for the secondary sleepiness and cognitive outcomes, or the rules used for any such analyses.

What can significance testing establish?

A statistical test evaluates data against a specified null hypothesis using an analysis model and decision rule. A p-value, when reported, describes how unusual the data would be under that model and null hypothesis; it does not measure the probability that a treatment is effective or safe. No p-value or inferential test is reported for the primary safety outcome. The registry record also does not report a prespecified significance level, adjustment for multiple comparisons, or a sample-size justification.

General statistical context: planning calculations based on an observed effect are illustrations of how a future study might be sized under stated assumptions. They are not evidence that the current study had adequate power, and they are not observed power. The registry's design rationale and sample-size justification are not reported in the registry record. No inferential conclusion should be drawn from the enrollment count alone.

What does the record say about other outcomes?

The registry lists six outcome measures and three analyses. The listed secondary measures cover sleepiness, patient and clinician global-improvement ratings, vigilance, and a One-back Task. Their numerical results, analysis methods, and handling of missing measurements are not reported in the registry record. General statistical context: outcome definitions and analysis choices are important because different scoring rules, time points, or models can yield different estimates. Without those details and the posted results, the secondary outcomes cannot be interpreted statistically.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and three analyses. The primary safety outcome includes adverse events, serious adverse events, and drug-related adverse events; the secondary outcomes address sleepiness, global impressions of improvement, vigilance, and a One-back Task. The registry record does not report a multiplicity strategy, such as a hierarchy of tests or an adjustment for examining several outcomes. It also does not identify which outcomes, if any, were intended to support confirmatory claims. General statistical context: when several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase, so interpretation depends on prespecified priorities and the approach to multiplicity.

Missing-data methods are not reported in the registry record. The record does not say how incomplete outcome measurements, withdrawals, missed periods, or unavailable assessments were handled. It also does not report whether the analyses included all randomized participants, only participants who received treatment, or a different population for each outcome. These details are particularly relevant in a crossover design, where a participant may have information for one period but not the other.

The safety population is defined as participants who signed the study-specific informed consent documents and received at least 1 dose of ERX-963 or placebo. The number analyzed under that definition is not reported in the registry record. The period-specific risk sets are listed as 7 and 7 for Cohort 1, and 5 and 5 for Cohort 2. The registry does not explain the relationship between those risk sets and sequence assignment or describe any exclusions.

As a result, the posted record supports a descriptive reading of the listed safety counts, but not a reconstruction of the full analysis population, missing-data handling, or multiplicity-adjusted interpretation of secondary outcomes.

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 serious adverse-event counts are 0 in all four listed cohort-period groups: the Cohort 1 placebo period, the Cohort 1 1 mg ERX-963 period, the Cohort 2 placebo period, and the Cohort 2 2 mg ERX-963 period. The corresponding numbers at risk are 7, 7, 5, and 5. Deaths are recorded as 0 in each group, and no serious-event terms are listed.

These are observed counts, not proof that the underlying risk is absent. General statistical context: when no event is observed in a limited group, the data still allow uncertainty about how often the event might occur in a broader population. The registry record does not provide confidence intervals for these counts or a formal comparison between ERX-963 and placebo.

Other adverse events are reported separately: 0 in the Cohort 1 placebo period, 1 in the Cohort 1 1 mg ERX-963 period, 2 in the Cohort 2 placebo period, and 1 in the Cohort 2 2 mg ERX-963 period. The registry does not report the event descriptions or separate counts for events judged drug-related. The counts should therefore be read as descriptive period-specific safety information, not as a complete comparison of treatment-related risk.

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

The registry record describes a randomized, double-blind crossover trial designed primarily to examine the safety and tolerability of single-day ERX-963 administration in adults with DM1. It reports no serious adverse events and no deaths in the listed cohort-period groups. It also reports other adverse events in some periods. Those observations are the extent of the posted safety findings summarized in the record.

They do not establish that ERX-963 is safe or unsafe, and they do not show that ERX-963 differs from placebo. The counts are limited, and the record does not provide confidence intervals, a paired treatment-effect estimate, or an inferential test. General statistical context: a study can record no serious event while still leaving uncertainty about uncommon events, especially when the number of participants observed is limited.

The record's primary outcome includes drug-related events, but separate counts for events assessed as related are not reported. The number of participants who experienced events in both treatment periods is also not reported. Without that detail, the period counts cannot be turned into a within-participant comparison. The event counts should not be interpreted as percentages, relative risks, or treatment-effect differences unless those estimates are reported from an appropriate analysis.

The listed secondary outcomes concern daytime sleepiness, global impressions of improvement, vigilance, and cognitive task performance. Their results are not reported in the registry record. The record therefore does not answer whether those measures changed or whether any change differed between ERX-963 and placebo. Its stated secondary aims are research questions, not evidence of an observed benefit.

Overall, the posted results are descriptive safety observations from a completed Phase 1 study. They can inform understanding of what was recorded during the study periods, but the registry record does not support broader conclusions about treatment effects, rare events, or the secondary outcomes.

13. Why This Trial Matters Statistically

This trial is statistically notable for its crossover structure. Each participant was intended to receive ERX-963 and placebo in separate periods, with randomized order and a washout between periods. General statistical context: a crossover can make within-person comparisons useful because each participant contributes information under both treatments. But that advantage depends on appropriate paired analysis and on the handling of period and carryover effects. The registry record does not report those analysis details, so the design alone cannot establish how the posted counts compare statistically.

The safety outcome also illustrates why counts need context. The record reports serious adverse-event and death counts of 0 in the listed periods, alongside other adverse-event counts of 0, 1, 2, and 1. Risk sets range across the reported cohort-period groups as 7 and 5 participants. Those observations are important to describe, but sparse counts provide limited precision. General statistical context: absence of an observed event is not equivalent to evidence that an event is impossible, and a count difference alone does not quantify a treatment effect.

The study aimed to examine potential sleepiness and cognitive outcomes in addition to safety. Keeping those objectives distinct matters: safety counts cannot answer questions about sleepiness or cognitive performance, and the absence of posted results for those secondary measures prevents their statistical interpretation.

The registry record therefore offers a focused example of the difference between a study objective, a design, and an analyzable result. It identifies the intended comparisons and reports some safety counts, while leaving the formal analysis, uncertainty estimates, and secondary-outcome results unreported. That distinction is central to reading early-phase clinical trial evidence accurately.

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 enrollment was 12, and the posted safety counts are divided between two cohorts and their treatment periods. This limits the amount of information available for describing uncommon events. The trial is identified as Phase 1, and the intervention was single-day administration; the record does not describe longer-term exposure or longer-term safety outcomes beyond collection from screening to the End of Study Visit, up to 57 days.

The registry does not report a formal treatment comparison, confidence intervals, p-values, or the statistical model used. It also does not report the washout duration, sequence-specific enrollment, participant-level event overlap, or whether period, order, and carryover were addressed in an analysis. Those omissions prevent reconstruction of a paired comparison from the posted group counts.

The adverse-event summary does not give descriptions for the other adverse events or separate counts for drug-related events. The registry lists no serious-event terms. Consequently, the severity, nature, timing, and investigator-assessed relationship of the non-serious events cannot be fully characterized from the record.

Results for the listed sleepiness and cognitive outcomes are not reported in the registry record. The record also does not report missing-data handling, outcome-specific analysis populations, a multiplicity strategy, or the rationale for the enrollment target. General statistical context: these details affect how estimates are interpreted and how much confidence can be placed in comparisons. The findings should therefore be read as limited descriptive safety information rather than as a complete account of all trial objectives or analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1 — NCT03959189.
• Registry record last updated 2021-06-23; status last verified 2021-05.
• Results first posted 2021-06-23.
• 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

The registry identifies NCT03959189 as a completed Phase 1 randomized, double-blind, placebo-controlled crossover trial in adults with DM1, with enrollment of 12. Participants were described as receiving ERX-963 and placebo in different periods, in randomized order, with a washout period. Cohort 1 included a 1 mg ERX-963 period; Cohort 2 included a 2 mg ERX-963 period.

The primary objective concerned adverse events, serious adverse events, and drug-related adverse events. The posted counts show no serious adverse events or deaths in the listed groups. Other adverse-event counts were 0, 1, 2, and 1 across the Cohort 1 placebo, Cohort 1 1 mg ERX-963, Cohort 2 placebo, and Cohort 2 2 mg ERX-963 periods. Results for the listed sleepiness and cognitive outcomes are not reported in the registry record.

Formal treatment-effect estimates, uncertainty intervals, analysis methods, missing-data handling, and multiplicity procedures are not reported in the registry record. The posted safety findings are therefore descriptive and do not establish comparative effects.