Study to Compare 2 Botulinum Type A Toxins in the Treatment of Glabellar Frown Lines: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Compare 2 Botulinum Type A Toxins in the Treatment of Glabellar Frown Lines (NCT04763265), a randomized phase 2 study. The primary outcome is Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 1 Points in FWS Score (at Maximum Frown) at Week 4 Visit Relative to Baseline, Based on Both the Investigators´ and the Subjects´ In-clinic Assessments..

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, controlled, parallel-group study with triple masking. Its official title describes a comparison of efficacy, time to onset, and duration of effect for botulinum type A toxins in the treatment of glabellar frown lines. The stated purpose was to provide preliminary comparative data on BoNT/A-DP versus Botox Cosmetic.

The registry reports enrollment of 208. The arm descriptions list Group A as n=100 and Group B as n=100. These entries do not establish how many participants were included in each efficacy or safety analysis; the registry record does not report those analysis-specific counts in the information available for this comparison. The listed enrollment and arm-description counts should therefore not be treated as interchangeable denominators.

The registry lists the study as completed, with a start date of 2020-06-24 and primary completion date of 2020-11-05. Croma-Pharma GmbH is identified as the sponsor. No additional information about recruitment, allocation concealment, randomization procedures, or which individuals were masked is reported in the registry record.

General statistical context: randomization is intended to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics. Masking is intended to reduce the influence of treatment knowledge on care, assessment, or reporting. These design features do not guarantee that groups are balanced in a particular trial, and the registry record does not provide enough detail to assess their implementation. A parallel-group design assigns participants to a group and follows the assigned groups, rather than describing a crossover between treatments.

The primary endpoint concerns a binary responder classification at Week 4. Secondary outcomes include responder classifications using alternative thresholds, assessments at other listed visits, onset and duration of effect, FACE-Q satisfaction, adverse events, and blood pressure change. The registry lists no statistical analyses for these outcome measures.

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: Of 208 enrolled participants, 200 met inclusion criteria and were randomized to treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The population consists of all randomized subjects who had a baseline visit and at least one post-dose in-clinic assessment with the 4-point Facial Wrinkle Scale by either the investigator or the subject at Weeks 1, 2, or 4.

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: The population consists of all randomized subjects who had a baseline visit and at least one post-dose in-clinic assessment with the 4-point Facial Wrinkle Scale by either the investigator or the subject at Weeks 1, 2, or 4.

6. Primary Endpoint

The registry lists the primary outcome as Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 1 Points in FWS Score (at Maximum Frown) at Week 4 Visit Relative to Baseline, Based on Both the Investigators´ and the Subjects´ In-clinic Assessments., measured over week 4.

The primary endpoint classifies participants as responders or nonresponders at the Week 4 visit of the first treatment cycle. To meet the stated responder definition, a participant had to have a Facial Wrinkle Scale score of 0 or 1 at maximum frown and an improvement of at least one point relative to baseline. The endpoint description says the classification is based on both investigator and subject in-clinic assessments. It does not specify the exact rule for combining those two assessments, so that detail cannot be inferred from the registry wording.

The Facial Wrinkle Scale is described as a four-point scale: 0 means no facial wrinkles, 1 means mild facial wrinkles, 2 means moderate facial wrinkles, and 3 means severe facial wrinkles. The endpoint therefore combines an absolute score threshold with a change-from-baseline condition. This distinguishes participants who reach a specified score from those whose score improves but remains outside the specified range.

General statistical context: a binary responder endpoint can make a clinical threshold easier to interpret than a mean change on a scale. However, categorizing a scale also discards information about the size of changes within each category. The Week 4 responder proportion would describe the share meeting the definition at that visit, not the full trajectory of scores over time. Participants with missing in-clinic assessments with the Facial Wrinkle Scale at baseline or Week 4 were assigned as nonresponders, as stated in the endpoint description.

The registry record does not report group-specific responder counts, proportions, an estimated treatment contrast, or uncertainty intervals for this endpoint. Thus, it does not permit a numerical interpretation of the primary efficacy comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

General statistical context: randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences in baseline characteristics between groups, so that a comparison can be interpreted more credibly as a treatment contrast. Randomization does not ensure exact balance in any individual trial, and the registry record does not describe the sequence-generation or allocation procedures. The designation “randomized” alone does not establish how those procedures were carried out.

The study is described as triple-masked. General statistical context: masking can reduce the possibility that knowledge of assignment influences participant reports, clinician behavior, outcome assessment, or other trial processes. The registry does not state which parties were masked or how masking was maintained. The endpoint includes both investigator and subject assessments, making assessment procedures relevant, but the record does not give further operational detail.

How should a binary endpoint be understood?

The primary outcome is a responder classification. Each participant either meets the stated criteria or does not. A group-level analysis would generally summarize the number or proportion of responders, then compare those summaries using a specified statistical method. The registry identifies the outcome as a count of participants but does not report the group-specific counts or the analysis method. Therefore, no treatment contrast can be reconstructed from the record.

General statistical context: binary outcomes can be summarized using proportions and compared through measures such as a difference in proportions or a ratio of proportions. Each measure answers a different question and can have different uncertainty. Choosing and interpreting a measure requires the analysis plan and observed data. No such comparison estimate is reported in the registry record, so no effect measure should be imputed.

The primary definition combines a score threshold and an improvement threshold. Such a composite rule can be useful when a study aims to require both a specified final state and a minimum change from baseline. It can also make the result sensitive to the selected cut points and to how assessments are combined. The registry says the endpoint is based on both investigator and subject assessments but does not specify the exact logical rule for combining them. It assigns missing baseline or Week 4 assessments as nonresponders, but does not describe other missing-data procedures.

Why does uncertainty matter?

General statistical context: an estimate is a summary of the observed data, while a confidence interval communicates uncertainty associated with that estimate under the chosen model and assumptions. Wider intervals indicate less precision than narrower intervals. A confidence interval is not a guarantee that the true effect lies in the interval; its interpretation depends on the statistical procedure and repeated-sampling framework. The registry does not report a primary effect estimate or confidence interval, so neither magnitude nor precision can be evaluated.

A test of statistical significance and an estimate of effect are related but distinct. A p-value measures how incompatible the observed data are with a specified null model, subject to the analysis assumptions. It does not quantify the probability that the null hypothesis is true, nor does it convey the practical importance of a result by itself. No primary p-value or test is reported in the record.

How do multiple outcomes and visits affect interpretation?

The registry lists secondary outcomes that cover multiple response definitions, assessment visits, assessors, time to onset, duration, satisfaction, adverse events, and blood pressure change. General statistical context: when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if no adjustment or prespecified testing strategy is used. A multiplicity plan can define which comparisons are confirmatory and how error rates are controlled. The registry record does not report such a plan, nor does it report analyses for these outcomes. This means the listed outcomes identify measurement intentions, not evidence that any particular comparison was statistically significant.

What is over-dispersion, and is it relevant?

General statistical context: over-dispersion occurs when observed variability is greater than a statistical model assumes. It can make standard errors too small and confidence intervals too narrow if ignored. It is especially relevant to count outcomes modeled with assumptions about their variance. The primary outcome is described as a participant count with a binary responder definition, but no model or dispersion estimate is reported. The registry record therefore does not establish whether over-dispersion was assessed or relevant to any analysis.

What can planning calculations establish?

The registry describes a sample-size illustration using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with an effect defined as a stated fraction of the observed effect. It says that these calculations are planning illustrations and not the trial’s own design. It also says the sample size was primarily based on clinical judgment and practical considerations. The registry does not report numerical planning outputs or a formal design justification. General statistical context: planned sample size is a design quantity based on assumptions; it is not observed power after a study has been completed. A planning illustration cannot substitute for reported outcome data or an effect estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes and assessment occasions. These include responder definitions using different improvement thresholds or assessment conditions, assessments at multiple weeks, time to onset, duration, satisfaction, adverse events, and blood pressure change. The primary outcome is also flagged as having several categories or time points and not being reduced to one comparison. The record does not report a multiplicity adjustment, a hierarchy of hypotheses, or a prespecified approach for selecting among comparisons. It also lists zero analyses. Consequently, the record does not establish which comparisons were intended to be confirmatory or how the risk of false-positive findings across multiple tests would be managed.

Missing-data handling is described for the primary endpoint in one specific circumstance: participants with missing in-clinic Facial Wrinkle Scale assessments at baseline or Week 4 were assigned as nonresponders. This rule makes those participants count as not meeting the responder definition in the primary endpoint description. It does not, by itself, explain how other missing observations, withdrawals, or unavailable secondary assessments were handled. Those procedures are not reported in the registry record.

The primary-outcome population is defined as randomized subjects with a baseline visit and at least one post-dose in-clinic scale assessment by an investigator or subject at Weeks 1, 2, or 4. The record does not describe other analysis populations or how participants who did not meet this definition were treated in analyses. In particular, it does not provide an analysis-specific participant flow or group denominators for the primary efficacy comparison.

These omissions limit reproducibility and interpretation. General statistical context: clear prespecification of outcome definitions, analysis populations, missing-data methods, and multiplicity handling helps readers distinguish planned inference from exploratory analysis. Without those details and the outcome analyses, the registry entry cannot establish the robustness of a comparative efficacy result.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lower limb fracture (1.0%).

The registry reports serious adverse events for the two listed groups. In Group A, 0 of the 100 listed at risk were affected by a serious adverse event; in Group B, 1 of the 100 listed at risk was affected. Deaths were listed as 0 in each group. For other adverse events, the posted counts are 11 of 100 in Group A and 15 of 100 in Group B. These are registry counts and should be read as descriptive entries, not as a complete analysis of comparative safety.

The serious-event term listed is Lower Limb Fracture, reported as 1.0%. The record does not identify the treatment group for this term in the listed term entry, describe the event’s timing or clinical course, or report whether investigators considered it related to treatment. A serious adverse event is not necessarily caused by the study intervention. The figures do not establish causation.

General statistical context: uncommon events are difficult to compare precisely when the number of events is small. Counts alone do not convey the uncertainty around a between-group difference, and the registry record does not report a comparative safety estimate or confidence interval. The “other adverse events” figures also do not identify the event types or severity in the information. As a result, the counts should not be interpreted as a complete safety profile or as evidence that one group has greater or lesser risk.

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

The record documents a Phase 2 randomized comparison of BoNT/A-DP and Botox Cosmetic for glabellar frown lines. It defines a Week 4 primary responder endpoint and lists secondary outcome areas, including repeated response assessments, onset and duration, satisfaction, adverse events, and blood pressure change. It also records serious and other adverse-event counts and reports no deaths in either listed group.

Those design and safety entries do not answer the primary efficacy question. No group-specific primary responder results, effect estimate, confidence interval, or primary statistical test is reported in the registry record. The record therefore does not show how the groups compared on the primary endpoint, how precise such a comparison might be, or whether any observed difference would be compatible with no difference under a specified analysis.

The study’s stated purpose was to provide preliminary comparative data, and the brief summary says sample size was based primarily on clinical judgment and practical considerations. That purpose should not be mistaken for a reported finding. Nor does completion status establish that the treatments were equivalent, different, or comparable in safety. The registry entry does not provide enough information to make those claims.

General statistical context: evidence about a treatment comparison depends on the observed outcomes, the analysis population, the statistical method, and uncertainty around the estimate. A non-significant test, if one were reported, would not by itself establish equivalence. Equivalence or non-inferiority requires a suitable design, a prespecified margin, and an analysis that addresses that question. Such details and results are not reported in the registry record.

The safety counts can be described, but they should not be treated as causal estimates or complete evidence about risk. The registry does not report event-level detail, attribution, or uncertainty estimates. Overall, the record is useful for identifying the intended comparison, design, endpoint, and limited posted safety information; it does not support a conclusion about comparative efficacy or a definitive comparative safety judgment.

13. Why This Trial Matters Statistically

This trial is statistically notable as a randomized, triple-masked, parallel-group comparison with a clearly described binary primary endpoint. The endpoint combines a Facial Wrinkle Scale threshold at maximum frown with a minimum improvement from baseline and draws on both investigator and subject assessments. That structure illustrates how clinical endpoints can combine a final-state criterion with change over time.

The record also illustrates why endpoint definitions and analysis results are not interchangeable. A detailed definition helps explain what investigators intended to count as a responder, but without group-specific counts and an analysis it cannot answer the comparative question. The registry explicitly does not reduce the primary outcome to one reported comparison and lists no analyses. This makes the distinction between trial design and statistical evidence especially important.

The sample-size description is also relevant. The stated aim was preliminary comparative data, and the brief summary says the sample size relied primarily on clinical judgment and practical considerations. General statistical context: design decisions based on practical considerations can be appropriate for exploratory work, but they do not supply the precision of an observed estimate or establish that a study can rule out a specified effect. The registry does not report a formal sample-size justification or the outcome analysis needed to evaluate precision.

Finally, the listed secondary outcomes span repeated visits and multiple assessment types. This makes prespecification and multiplicity handling important for interpretation, yet the registry does not report a testing strategy or secondary analyses. The study therefore serves as a useful example of how a record can communicate design intentions and selected safety counts while leaving the central comparative efficacy result unavailable.

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 central limitation is that the registry record does not report the primary efficacy comparison. There are no group-specific responder counts or proportions, estimated treatment contrast, confidence interval, or primary p-value in the record. The primary outcome is flagged as having several categories or time points and not being reduced to one comparison, and the record lists zero analyses. This prevents assessment of the direction, magnitude, and precision of the primary result.

There is an unresolved difference between the reported enrollment of 208 and the group descriptions that each list n=100. The record does not explain this difference or give analysis-specific denominators. It would be inappropriate to infer how the remaining participants were distributed, whether they were analyzed, or why they are not reflected in the arm descriptions.

The endpoint description does not specify the exact rule for combining investigator and subject assessments. It gives a missing-assessment rule for baseline or Week 4, but does not describe other missing-data procedures, participant disposition, or analysis populations beyond the stated primary-outcome population definition. The record also does not report the statistical model, estimation method, or multiplicity strategy.

Safety information is limited to group-level counts and a serious-event term. The registry does not provide detailed event narratives, treatment attribution, timing, or comparative uncertainty. The listed adverse-event counts therefore cannot establish cause or provide a full account of safety.

Other details not reported in the registry record include the randomization procedures, allocation concealment, masking implementation, formal sample-size justification, and the identities of the parties covered by triple masking. These limitations constrain assessment of trial conduct and analysis beyond the design labels and descriptions that are recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Compare 2 Botulinum Type A Toxins in the Treatment of Glabellar Frown Lines — NCT04763265.
• Registry record last updated 2025-03-18; status last verified 2021-01.
• Results first posted 2025-03-18.
• 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 describes a completed Phase 2 randomized, controlled, triple-masked, parallel-group study sponsored by Croma-Pharma GmbH. It compared BoNT/A-DP with Botox Cosmetic for glabellar frown lines. The record reports enrollment of 208 and arm descriptions listing n=100 for each group.

The primary endpoint was a Week 4 responder classification based on a Facial Wrinkle Scale score of 0 or 1 at maximum frown and improvement of at least one point from baseline, using investigator and subject assessments. Missing baseline or Week 4 in-clinic scale assessments were assigned as nonresponders. The registry does not report the primary efficacy comparison or any analyses.

Safety entries list 0 serious adverse events and 0 deaths in Group A, and 1 serious adverse event and 0 deaths in Group B. Other adverse events were listed for 11 participants in Group A and 15 in Group B. The registry’s stated purpose was to provide preliminary comparative data; its brief summary says sample size was based primarily on clinical judgment and practical considerations.