Safety Study of DWP-450 (Botulinum Toxin, Type a) to Treat Glabellar Lines - EV-006: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Study of DWP-450 (Botulinum Toxin, Type a) to Treat Glabellar Lines - EV-006 (NCT02428608), a na phase 2 study. The primary outcome is The Safety of Repeat DWP-450 Treatments - Proportion of Subjects With at Least One Adverse Event Over 1 Year.

2. Clinical Question

In plain terms, EV-006 was intended to document adverse events over the stated follow-up period among adults receiving DWP-450 for glabellar lines. It was not designed as a like-for-like comparison between treatment groups: only one study group is described. As a result, the record can convey what safety events were reported among enrolled participants, but it cannot establish how those reports compare with a separate untreated or actively treated group.

The study title and outcome descriptions are not fully aligned. The official title calls the study single dose, while the brief objective refers to multiple doses and the primary outcome title refers to repeat treatments. The registry record does not explain this difference or specify the treatment schedule. This distinction matters when interpreting a safety follow-up that spans 365 days: the record identifies the period being assessed, but does not provide enough detail to reconstruct the timing or number of treatments each participant received.

3. Trial Design

EV-006 is listed as a Phase II, completed, open-label, single-group study sponsored by Evolus, Inc. It enrolled 570 participants and studied DWP-450, a Botulinum toxin, Type A product, for moderate-to-severe glabellar lines. The registry record lists the start as 2015-05 and primary completion as 2016-10. Allocation is not applicable, and masking is none. These design details indicate that the registry does not describe random assignment or blinded outcome assessment.

The stated objective was to demonstrate the safety of multiple doses of DWP-450 in adults. The official title instead describes a single-dose trial, and the primary outcome title refers to repeat DWP-450 treatments. The record does not resolve these differences. It also does not report the dose, treatment schedule, or whether participants received the same exposure. Those details should not be inferred from the outcome wording alone.

The primary outcome concerns the proportion of participants with at least one adverse event occurring from Day 0 through Day 365. The registry record says that the primary safety analysis involved calculating this proportion. However, a numerical result for that primary endpoint is not reported in the registry record. Separate posted safety information lists 7 participants with serious adverse events and 228 with other adverse events, each among 570 participants at risk. These figures are useful descriptions of the reported safety categories, but they do not by themselves supply the missing primary endpoint result.

Because there is no comparison group, differences between DWP-450 and another intervention cannot be estimated from this study design. The open-label design also means the record does not describe masking of participants or investigators. The registry record does not report a statistical analysis plan, sample-size justification, or details of an interim analysis. The enrollment total is a study characteristic, not evidence by itself that the study had a particular degree of statistical precision.

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:

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 The Safety of Repeat DWP-450 Treatments - Proportion of Subjects With at Least One Adverse Event Over 1 Year, measured over 365 days.

The primary endpoint is described as the proportion of participants with at least one adverse event occurring from Day 0 through Day 365. It is a participant-level safety measure: each participant is classified according to whether at least one event occurred during the specified period, rather than being counted repeatedly for each event. The registry record identifies the unit as participants and describes the primary analysis as a calculation of this proportion.

Such an endpoint is used to summarize how commonly participants experienced at least one event during a defined follow-up period. A fixed observation window gives the proportion a clear time frame, which is important because a participant followed for longer has more opportunity to experience an event. The stated period is 365 days, but the registry record does not report how follow-up completeness was handled or how missing observations were treated.

The primary endpoint's numerical result is not reported in the registry record. The posted safety figures list participants with serious adverse events and participants with other adverse events, but the record does not establish that either category alone is the exact primary endpoint. Nor does it report whether participants could appear in both categories or how the categories relate to the primary endpoint definition. It would therefore be inappropriate to calculate the primary proportion from those figures or treat either count as its result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: a single-group safety study describes outcomes observed among participants who received the intervention. It can estimate the frequency of recorded events within that group, but it does not directly estimate a treatment-versus-control difference. Without a comparator, observed events cannot be separated statistically into those associated with the intervention and those that might have occurred for other reasons. This is a design limitation, not a judgment about any particular event.

What does a participant-level safety endpoint count?

The primary endpoint is framed as the proportion of participants with at least one adverse event during the specified period. This differs from counting all events: a participant with multiple events still meets the participant-level definition of having at least one. The registry describes the endpoint and its time frame, but does not report the numerical proportion or its confidence interval. The separate posted counts of serious and other adverse events should not be substituted for the primary endpoint, because the record does not give the relationship between those categories and the primary definition.

Why does the follow-up window matter?

General statistical explanation: an event proportion is meaningful only in relation to the period during which events were observed. Longer observation can create more opportunity to record events, so results from different follow-up periods are not automatically comparable. EV-006 identifies a period from Day 0 through Day 365. The registry record does not report details of participant-level follow-up completeness, censoring, or how observations ending before Day 365 were handled. Consequently, readers cannot determine from this information whether all participants contributed the full period or how incomplete follow-up affected the analysis.

How should event counts and proportions be distinguished?

A count states how many participants were recorded in a category. A proportion relates a count to a defined denominator. The posted record lists 7 participants at risk and affected counts of 7 for serious adverse events, and 570 at risk and 228 affected for other adverse events. It does not report a confidence interval for these figures in the information available for this analysis. No new proportion should be inferred from the counts, and the two affected counts should not be combined: the record does not establish whether the categories overlap or use identical event rules.

General statistical explanation: uncertainty around a proportion can be summarized with a confidence interval. The interval reflects sampling variability under a chosen statistical method and assumptions; it is not a guarantee that the true value lies within a particular range. A confidence interval can also help distinguish a precise estimate from one with substantial uncertainty. The registry record does not report a confidence interval for the primary safety outcome, so the precision of that outcome cannot be described.

What does open-label, single-group design imply?

The record lists masking as none and describes a single group. General statistical explanation: lack of masking can affect how participants report symptoms and how investigators identify, classify, or document events. This does not show that reporting was biased in this study; it identifies a possible source of measurement uncertainty. A single-group design also means that background event frequency is not directly observed in a concurrent comparator group. As a result, event counts are descriptive and cannot establish comparative risk from this design alone.

What do the sample-size assumptions represent?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions describe a two-arm planning framework, while EV-006 is listed as a single-group study with allocation not applicable. The registry record does not report the numerical planning results or a trial-specific sample-size justification. Such planning quantities, where available, would be illustrations under chosen assumptions, not observed power and not a substitute for the study's outcome results.

General statistical explanation: a sample-size calculation asks how much information a proposed design may need to detect a specified effect under assumed variability and error rates. It does not establish that the effect is real, nor does it measure the probability that a completed study has demonstrated a treatment effect. For a single-group safety study, planning goals may differ from a two-arm comparison, but the registry record does not describe the rationale used for the enrollment of 570 participants.

The record reports no analysis count and does not describe an adjusted model. No specific test, confidence-interval method, or method for handling repeated events is reported in the registry record. These absences matter because different methods can address different questions: whether participants experienced any event, how many events occurred, and when events occurred are distinct outcomes. The posted primary endpoint is participant-level and binary, but the statistical procedures beyond the stated calculation of a proportion are not reported.

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("Botulinum Toxin, Tyoe A")
n      <- c(570)
events <- c(235)
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  Botulinum Toxin, Tyoe A  570  235  41.2  37.2  45.4  37.3  45.3  37.3  45.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled. Multiplicity arises when several outcomes, comparisons, or analyses are tested, because repeated testing can increase the chance of a nominally notable result. The record lists two outcome measures, but does not provide a multiplicity strategy or explain whether the primary safety endpoint was the sole confirmatory outcome. No p-value or inferential result for the primary endpoint is reported, so the record does not permit an assessment of any multiplicity adjustment.

Missing-data handling is also not reported in the registry record. In a safety follow-up extending through Day 365, interpretation can depend on how participants with incomplete follow-up are handled and whether all participants contribute the same observation period. The record does not give the number with complete follow-up, describe withdrawals, or state whether missing outcomes were imputed, excluded, or handled by another method. These details should not be guessed.

The analysis population is not reported in the registry record. It is therefore unclear whether the primary safety analysis included all enrolled participants, those who received treatment, those with available follow-up, or another population. The at-risk counts are listed as 570 for each of the serious and other adverse event categories, but that does not establish the population used for the primary endpoint. The registry also does not report a statistical analysis plan or an interim-analysis approach. Without those details, the analysis framework and its safeguards cannot be reconstructed.

12. Safety Results

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

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: carotid artery stenosis (0.2%), overdose (0.2%), small intestinal obstruction (0.2%), breast cancer (0.2%), uterine leiomyoma (0.2%).

The registry lists 7 participants with serious adverse events among 570 at risk, and 228 participants with other adverse events among 570 at risk. These are reported counts for separate safety categories. The record does not say whether the categories are mutually exclusive, so the counts should not be added or interpreted as a total number of distinct participants with any adverse event.

For serious adverse events, the record lists Carotid artery stenosis, Overdose, Small intestinal obstruction, Breast cancer, Uterine leiomyoma, and Anxiety, each with a reported value of 0.2%. These are event terms in the registry record; the information does not establish that the intervention caused them. The record does not report timing, clinical details, relatedness assessments, or outcomes for these events. The death count is not reported in the registry record.

The safety counts are not the reported numerical result for the primary endpoint, which concerns the proportion with at least one adverse event from Day 0 through Day 365. That result is not reported in the registry record. The figures should therefore be read as descriptive safety information, not as a complete account of the primary analysis or as a comparison with another group.

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

The record establishes that EV-006 was a completed, open-label, single-group Phase II study with 570 enrolled participants, and that it evaluated DWP-450 in adults with moderate-to-severe glabellar lines. It also specifies a primary safety question: the proportion of participants with at least one adverse event from Day 0 through Day 365. The posted safety information gives counts for participants with serious and other adverse events. These registry entries describe the study's scope and some reported safety observations.

The record does not report the numerical result for the primary endpoint, its confidence interval, or a statistical comparison. It therefore does not show the estimated proportion for that endpoint or how precise such an estimate would be. The serious and other adverse event counts cannot be used to reconstruct the missing primary result because the record does not specify whether categories overlap or how they map onto the endpoint definition.

The single-group design means the study does not provide a concurrent control group for comparing event frequency. The counts are observations among study participants, not estimates of the difference between DWP-450 and another treatment. The registry record also does not report enough detail to attribute any listed event to the intervention. The listed serious event terms should not be interpreted as causal findings.

The record does not report the treatment schedule, analysis population, missing-data approach, or a full statistical plan. Its official title describes a single dose, while other descriptions refer to multiple doses or repeat treatments; that discrepancy is not explained. These omissions constrain what can be concluded about exposure and analysis. The appropriate reading is descriptive: the registry documents the study design and selected safety counts, while leaving the primary endpoint result and several key interpretive details unreported.

14. Why This Trial Matters Statistically

EV-006 illustrates an important distinction in clinical-trial reporting: describing an endpoint is not the same as reporting its result. The registry record gives a clear safety question and follow-up window, but does not provide the primary endpoint's numerical estimate. Without that estimate, readers cannot assess the size or precision of the principal outcome, even though participant enrollment and separate event counts are reported.

The study also demonstrates why design determines the scope of statistical interpretation. A single-group, open-label study can document events among its participants, but it cannot make a randomized comparison with a control group that is not part of the design. The posted event counts are therefore descriptive. They should not be converted into a claim about relative safety or causal attribution.

Reporting categories need careful interpretation as well. The registry separately lists serious and other adverse events, but does not state whether participants can occur in both categories or how those categories relate to the primary endpoint. Treating them as disjoint groups or combining them would go beyond the record. The listed serious event terms likewise describe reported events, not established causes.

Finally, the distinction between a planned sample-size illustration and an observed trial result is important. The stated planning assumptions describe a two-arm framework, whereas the study itself is single-group; the registry does not report a trial-specific sample-size rationale or numerical planning output. These gaps show why analysis assumptions, population definitions, and outcome results are all needed to interpret a safety study fully. The enrollment count alone does not answer questions about precision or analysis quality.

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 does not report a numerical result for the primary endpoint, a confidence interval, or the analysis population. It also does not report how incomplete follow-up or missing safety observations were handled. These omissions prevent assessment of the primary estimate and its precision and make it difficult to determine exactly who contributed to each analysis.

The record lists a single group, no masking, and no comparator. Thus, the posted adverse event counts are descriptive and do not support a direct treatment-versus-control comparison. The record also does not provide event-level timing, relatedness assessments, clinical details, or outcomes for the listed serious adverse events. A death count is not reported in the registry record.

There is an unresolved difference between the official title, which describes a single-dose trial, and other descriptions referring to multiple doses and repeat treatments. The treatment schedule and actual exposure are not reported in the registry record. The relationship between serious and other adverse event categories is also not specified, so they should not be treated as mutually exclusive or combined.

The registry does not report a statistical analysis plan, sample-size justification, multiplicity handling, or interim-analysis approach. Although planning assumptions are described for a two-arm calculation, the study is single-group, and no numerical planning results are reported. These limitations restrict reconstruction of the intended analysis and interpretation of the posted safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety Study of DWP-450 (Botulinum Toxin, Type a) to Treat Glabellar Lines - EV-006 — NCT02428608.
• Registry record last updated 2019-04-24; status last verified 2019-04.
• Results first posted 2019-02-05.
• 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

EV-006 (NCT02428608) is a completed Phase II, open-label, single-group study sponsored by Evolus, Inc. It enrolled 570 adults for evaluation of DWP-450, Botulinum toxin, Type A, for moderate-to-severe glabellar lines. The registry lists a start of 2015-05 and primary completion of 2016-10.

The primary safety endpoint concerns the proportion of participants with at least one adverse event from Day 0 through Day 365. Its numerical result is not reported in the registry record. Posted safety information lists 7 participants with serious adverse events and 228 with other adverse events, with 570 at risk in each category. The record does not report a comparator, confidence interval, analysis population, or missing-data method. It also does not resolve the difference between single-dose wording in the official title and descriptions referring to multiple or repeat treatments.