Efficacy and Safety of DaxibotulinumtoxinA (DAXI) for Injection for Treatment of Forehead Lines (Frontalis): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of DaxibotulinumtoxinA (DAXI) for Injection for Treatment of Forehead Lines (Frontalis) (NCT03786770), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With None or Mild in FHL Severity at Maximum Eyebrow Elevation.

2. Clinical Question

This study addressed a treatment setting in which forehead lines and the glabellar complex were treated together. Its design evaluated successive dose cohorts rather than comparing DAXI with an untreated group or a separate active treatment. The recorded endpoint focuses on forehead-line severity at maximum eyebrow elevation, a dynamic facial movement condition. It does not, by itself, describe outcomes at rest or establish how participants felt about their appearance or treatment.

3. Trial Design

The registry identifies this as a completed Phase 2a, multicenter, open-label, dose-escalation study. Enrollment was 61. The study began on 2019-01-24, and primary completion was recorded as 2020-03-09. Its allocation is listed as non-randomized, its masking as none, and its model as sequential.

Four cohorts are described. Each received DAXI for forehead lines and glabellar lines. The safety listings identify the cohorts as DAXI 40 U for glabellar lines paired with 12 U, 18 U, 24 U, or 30 U for forehead lines. The record calls these Dose A, Dose B, Dose C, and Dose D, respectively. It does not report the operational rules used to move between doses, or whether any dose-escalation decisions were based on interim safety or efficacy reviews.

Because allocation was not randomized and there was no masked comparison, cohort outcomes cannot be interpreted as if dose assignment had been randomized. Sequential cohorts may differ in ways other than dose; the registry record does not describe cohort-specific participant characteristics that could be used to assess this. The record also does not identify a placebo or active control arm.

The brief study summary describes treatment of moderate or severe dynamic forehead lines in conjunction with treatment of the glabellar complex. The number and locations of participating centers, recruitment details, and participant eligibility criteria beyond this description are not reported in the registry record. The study is marked completed, but its primary endpoint result and analysis 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

Analysis population for the primary outcome, as defined in the registry: The FHL-evaluable population

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: Intent to treat population

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With None or Mild in FHL Severity at Maximum Eyebrow Elevation, measured over Week 4 After FHL Treatment.

The primary endpoint is the percentage of participants in the FHL-evaluable population whose forehead-line severity was scored as none or mild at maximum eyebrow elevation. The registry defines this response as a score of 0 or 1 on the four-point Investigator Global Assessment Forehead Wrinkle Severity scale, where 0 is the lowest severity and 3 is the highest. The assessment is described as occurring 4 weeks after FHL treatment. The timeframe field labels this Week 4 after FHL treatment, while the endpoint description also calls the assessment Week 6. This timing discrepancy is not resolved in the registry record.

In general, a categorical endpoint such as this turns an ordered severity assessment into a responder outcome: participants either meet the specified threshold or do not. Reporting the percentage meeting that threshold can make the endpoint easier to interpret as a proportion of the assessed population. However, it does not convey the full distribution of severity scores, the size of change for each participant, or participant-reported experience. Those details are not reported in the registry record.

The endpoint is specific to a facial movement condition—maximum eyebrow elevation—and to the stated assessment time. It should not be extended to other times or assessment conditions. Although the endpoint definition is recorded, its observed percentage and uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods concern how outcomes are summarized and compared, how uncertainty is represented, and how missing or repeated measurements are handled. In this study, the registry record identifies the primary endpoint and design, but lists no analyses. The statistical plan, including the planned estimands, model, and inferential procedures, is not reported in the registry record. The explanations below describe general statistical principles and clarify what the recorded information can and cannot establish.

What does the responder percentage represent?

In general, a responder percentage is the proportion of an analyzed population whose measurements meet a prespecified definition. Here, the stated definition is a score of 0 or 1 for forehead-line severity at maximum eyebrow elevation, using the IGA-FHWS scale. The denominator would be the relevant analysis population with outcome information under the chosen analysis rules. The record names the FHL-evaluable population but does not report its size, the responder count, or the resulting percentage.

A threshold-based endpoint is straightforward to communicate, but it simplifies an ordered scale. A participant scoring just within the response category and a participant at the lowest severity score both count as responders, while the categories above the threshold count as nonresponders. The percentage therefore answers the threshold question, not every question about the distribution or degree of severity. A full account might also describe score distributions or changes, but those results are not reported in the registry record.

Why does the design affect interpretation?

In general, random allocation helps balance measured and unmeasured prognostic factors across comparison groups, on average. This study is recorded as non-randomized and sequential, with no masking. The four dose cohorts are not a randomized control comparison. Thus, even if cohort-specific response estimates were available, differences would be descriptive unless supported by an appropriate analysis and justified assumptions. The registry record does not report such an analysis.

Open-label assessment can also matter when outcomes depend on judgment. The primary endpoint uses an investigator global assessment. In general, masking can reduce the risk that knowledge of treatment assignment influences assessment. Here, masking is listed as none; the record does not describe assessment safeguards or independent review. This does not establish that assessments were biased, but it is relevant context when interpreting a subjective severity rating.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated effect or percentage under the assumptions of the analysis. It is not a guarantee that the true value lies within the interval, and its interpretation depends on the method and design. A narrow interval generally indicates greater precision than a wide interval. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated.

In general, a hypothesis test addresses compatibility between observed data and a specified null model. A p-value does not measure the size or clinical importance of an effect, and it does not give the probability that a treatment is effective. The registry record lists no analyses and no p-values. There is therefore no reported hypothesis-test result to interpret.

How should planning illustrations be read?

In general, sample-size planning calculations ask how many participants might be needed under specified assumptions about a target effect, variability, allocation, and error rates. The planning assumptions recorded for this study use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial used those choices in its own design.

The recorded sample-size assumptions describe planning illustrations computed from an observed effect, but the primary endpoint result needed to identify that effect is not reported in the registry record. Any such calculation is therefore an illustration based on its assumptions, not observed power. Sample-size planning does not establish that an actual trial had adequate precision, and a planning calculation cannot replace an estimate with its uncertainty.

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. It can make standard errors too small if not accommodated, leading to confidence intervals that are too narrow or tests that are too liberal. The registry record does not report a model for the primary endpoint or any evidence that over-dispersion was assessed. Since the endpoint is a binary responder outcome, the relevant modeling and variance assumptions would depend on the actual analysis; those details are not reported.

What can be recalculated?

A recalculated estimate would use posted summary data to reproduce a simple, unadjusted calculation. It would not be equivalent to a sponsor's potentially adjusted or otherwise prespecified analysis. In this case, the registry record contains no primary outcome counts or percentages and no analyses, so no efficacy estimate or comparison can be recalculated. There is no basis to infer a treatment effect from the design description or safety counts.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1: DAXI 40 U GL / 12 U FHL", "Cohort 2: DAXI 40 U GL / 18 U FHL", "Cohort 3: DAXI 40 U GL / 24 U FHL", "Cohort 4: DAXI 40 U GL / 30 U FHL")
n      <- c(14, 15, 16, 15)
events <- c(12, 13, 15, 15)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1: DAXI 40 U GL / 12 U FHL  14  12  85.7  57.2  98.2  60.1  96.0  59.5  95.7
ARM  Cohort 2: DAXI 40 U GL / 18 U FHL  15  13  86.7  59.5  98.3  62.1  96.3  61.7  96.0
ARM  Cohort 3: DAXI 40 U GL / 24 U FHL  16  15  93.8  69.8  99.8  71.7  98.9  71.3  98.5
ARM  Cohort 4: DAXI 40 U GL / 30 U FHL  15  15  100.0  78.2  100.0  79.6  100.0  79.4  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the percentage with none or mild forehead-line severity at maximum eyebrow elevation. It does not report a statistical analysis plan, a hierarchy of outcomes, or any method for controlling multiplicity. The single listed primary endpoint does not by itself establish that only one statistical comparison was planned: analyses across cohorts, time points, or subgroups could create multiple opportunities for inference. Whether such analyses were planned or adjusted for is not reported in the registry record.

The record identifies the FHL-evaluable population for the primary endpoint, but does not define the rules for membership in that population or give its size. It does not report the number of missing assessments, reasons for missingness, or how missing endpoint values were handled. In general, missing-data methods can affect estimates when the availability of outcomes is related to participants' characteristics or outcomes. Without the analysis population and missing-data approach, it is not possible to assess that potential influence.

The registry reports 0 analyses. It therefore does not provide an endpoint estimate, confidence interval, p-value, or analysis details to assess. Interim analyses, stopping rules, and any prespecified approach to multiplicity or missing data are not reported in the registry record. These omissions limit the ability to reconstruct the intended statistical inference or judge whether the posted outcome definition and analysis correspond to a prespecified plan.

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 figures are listed by cohort. For serious adverse events, the record gives 0 affected participants in Cohort 1, 0 in Cohort 2, 0 in Cohort 3, and 0 in Cohort 4. Deaths are also recorded as 0 in each cohort. For other adverse events, the record gives 5 affected participants in each of the four cohorts. The corresponding at-risk counts are 14, 15, 16, and 16.

These figures are counts from the registry record. They are not comparative risk estimates, and no adjustment for differences between cohorts is reported. The record does not describe the other adverse events, their severity, timing, duration, or whether investigators considered them related to treatment. It also does not give detail about adverse-event collection procedures. Accordingly, the counts should not be taken as a complete characterization of safety or as evidence that an event was or was not caused by DAXI.

In general, zero recorded events in a cohort does not prove that the underlying risk is zero. The amount of information depends in part on the number observed and the extent of follow-up, and the registry record does not provide a detailed follow-up description for safety. The listed counts are useful for describing what was recorded, but they do not establish comparative safety between doses.

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

The record shows that a completed Phase 2a study evaluated DAXI for dynamic forehead lines alongside glabellar-line treatment, using four sequential, non-randomized dose cohorts. It defines a primary responder outcome based on investigator-rated forehead-line severity at maximum eyebrow elevation. It also records serious adverse-event counts, other adverse-event counts, and deaths by cohort.

However, the primary outcome result is not reported in the registry record. No endpoint response percentage, response count, confidence interval, or statistical test is listed. As a result, the record cannot establish how often participants met the endpoint definition, how precise an estimate might be, or whether response differed across cohorts. The absence of a reported result is not evidence of no effect or of a particular effect.

The design also limits what a dose comparison could mean. Sequential, non-randomized cohorts do not provide the same basis for causal comparison as randomized groups. Without a control group, the record cannot quantify outcomes relative to no treatment or another treatment. Cohort differences, if observed in results outside this record, would need cautious interpretation and an appropriate analysis.

The safety listing records no serious adverse events or deaths in the cohorts, and records other adverse events in each cohort. These counts do not establish that serious events cannot occur, and the lack of event descriptions and treatment-relatedness assessments limits interpretation of the other adverse events.

In general, a trial record is most informative when it reports the outcome estimates, their uncertainty, analysis populations, and methods alongside the design. Those elements are not available for the primary endpoint in this registry record. The trial's design and endpoint can be described, but the posted information does not support a conclusion about the magnitude or precision of the primary outcome.

14. Why This Trial Matters Statistically

This trial is statistically notable because it combines a sequential dose-escalation design with a subjective investigator-rated primary outcome and no randomization or masking. Those features make it important to distinguish a study's descriptive purpose from a controlled treatment comparison. The cohort structure can help organize observations across dose levels, but it does not, on its own, ensure that participants in the cohorts are comparable.

The primary endpoint also illustrates the trade-off in using a responder threshold. A percentage meeting a defined severity cutoff can be readily understood, while concealing changes within the responder and nonresponder categories. The scale's meaning and the assessment condition—maximum eyebrow elevation—are therefore central to interpreting the endpoint. The timing field and endpoint description use different week labels for the assessment; the record does not clarify that inconsistency.

Statistical interpretation depends on more than whether an endpoint is defined. It also depends on the result, its precision, the population analyzed, handling of missing observations, and the analysis plan. The registry identifies the FHL-evaluable population but does not report its size, endpoint results, uncertainty, or analysis. This means the study's main statistical question cannot be answered from the registry record alone.

The safety counts offer a further lesson in restraint: a count of zero serious events is a description of observed events, not a demonstration that risk is absent. Likewise, the repeated count of other adverse events does not explain the types or causes of those events. The record supports a bounded account of what was listed, while leaving important questions about efficacy, precision, and safety characterization unresolved.

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 most important limitation for interpreting the primary question is that the registry record does not report the primary endpoint results or analyses. It also does not report confidence intervals, p-values, or the size of the FHL-evaluable population. Therefore, neither the observed response nor its precision can be assessed from this record.

The design is non-randomized, sequential, and open-label, with no masking. These features mean the dose cohorts are not a like-for-like control comparison and leave potential for cohort differences and assessment effects. The record does not provide cohort-specific baseline characteristics or analysis methods that might help evaluate those concerns. It also does not describe a separate control group.

The endpoint timing is not fully consistent in the record: the timeframe field states Week 4 after FHL treatment, while the endpoint description identifies the assessment as Week 6. No clarification is reported. The endpoint is also limited to investigator-rated severity at maximum eyebrow elevation and does not report other assessment conditions or participant-reported outcomes.

For safety, the record gives counts but not descriptions of the other adverse events, their seriousness details, or their assessed relationship to treatment. The safety follow-up duration and collection methods are not reported in the registry record. Missing endpoint data, their reasons, and their handling are also not reported. Finally, while the study is described as multicenter, the number of centers is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of DaxibotulinumtoxinA (DAXI) for Injection for Treatment of Forehead Lines (Frontalis) — NCT03786770.
• Registry record last updated 2023-02-16; status last verified 2023-01.
• Results first posted 2023-02-16.
• 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 record describes NCT03786770, a completed Phase 2a, multicenter, open-label, sequential dose-escalation study of daxibotulinumtoxinA for dynamic forehead lines in conjunction with glabellar-line treatment. Enrollment was 61. The study began on 2019-01-24, with primary completion recorded on 2020-03-09. Allocation is listed as non-randomized, and masking as none.

Four cohorts received DAXI 40 U for glabellar lines alongside forehead-line doses of 12 U, 18 U, 24 U, or 30 U. The primary endpoint was the percentage of the FHL-evaluable population with none or mild severity at maximum eyebrow elevation, defined as a score of 0 or 1 on the IGA-FHWS scale. The endpoint result and statistical analyses are not reported in the registry record.

The safety listing records 0 serious adverse events and 0 deaths in each cohort, and 5 participants with other adverse events in each cohort. Descriptions of those other events are not reported in the registry record.