A Study to the Assess the Change in Condition and Adverse Events of OnabotulinumtoxinA X Injection in Adult Participants With Glabellar Lines: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to the Assess the Change in Condition and Adverse Events of OnabotulinumtoxinA X Injection in Adult Participants With Glabellar Lines (NCT05100199), a randomized phase 2 study. The primary outcome is Percentage of Participants With Achievement of ≥ 1-grade Improvement From Baseline as Rated by Investigator Using the Clinician Glabellar Lines Scale..

2. Clinical Question

3. Trial Design

This was a randomized, placebo-controlled, parallel-group Phase 2 study of OnabotulinumtoxinA X in adults with moderate to severe glabellar lines. The registry record lists the study as multicenter, double-blind, and quadruple-masked. It does not explain how those masking descriptions relate to one another or identify the masked roles. Allocation was randomized, and participants were assigned to placebo or one of three OnabotulinumtoxinA X dose groups. Each listed injection was given into the Glabellar Complex on Day 1.

The registry record lists 328 participants enrolled and the study status as completed. The listed study start date is 2021-10-06, and the primary completion date is 2022-12-02. Allergan is listed as the sponsor. The arm descriptions identify Dose A, Dose B, and Dose C, but do not state the dose amounts. The allocation ratio, randomization method, site count, eligibility details beyond adult participants with moderate to severe glabellar lines, and participant baseline characteristics are not reported in the registry record.

The primary outcome is a responder measure: the percentage of participants with at least a 1-grade improvement from baseline on the investigator-rated Clinician Glabellar Lines Scale between Day 1 and Day 30. Secondary outcomes include attaining none or mild severity, improvement in a satisfaction-questionnaire impact domain among participants with baseline scores of 14 points or greater, and satisfaction with treatment. The latter outcome is assessed from Day 1 to Day 60. The registry record does not report the study's original sample-size justification, detailed statistical analysis plan, or interim-analysis arrangements.

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:

Analysis population for the primary outcome, as defined in the registry: Multiple Imputation - Intent-to-Treat Population Estimated responder is the average number of responders across 5 imputed datasets. Confidence interval for responder rate is calculated using normal approximation.

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 Achievement of ≥ 1-grade Improvement From Baseline as Rated by Investigator Using the Clinician Glabellar Lines Scale., measured over Day 1 to Day 30.

The primary endpoint is the percentage of participants rated by an investigator as having at least a 1-grade improvement from baseline on the Clinician Glabellar Lines Scale. The scale assesses glabellar-line severity at maximum contraction, with categories from 0 - None to 3 - Severe. The primary measurement timeframe is Day 1 to Day 30.

This is a binary responder endpoint: each participant is classified according to whether the required improvement was achieved, and the group result is expressed as a percentage. A responder definition can make a clinical scale easier to interpret as a proportion meeting a specified threshold. It also simplifies the outcome into achieved or not achieved, so it does not retain all detail about the amount of change for participants who improve by different amounts. The primary definition counts improvement of at least one grade; it is not the same as a measure of average scale change.

The registry describes the primary population as Multiple Imputation - Intent-to-Treat. It states that the estimated responder is the average number of responders across 5 imputed datasets and that the confidence interval for the responder rate uses a normal approximation. The registry record does not report further detail about the imputation model or the handling of particular types of missing observations.

7. Results Posted in the Registry

• OnabotulinumtoxinA X Dose A: 95.6% (86/90) versus 17.8% (8/45) on control; risk difference 77.8 percentage points (95% CI 65.8 to 89.7), risk ratio 5.38 (2.86–10.09); unadjusted two-proportion z-test p = <0.001.
• OnabotulinumtoxinA X Dose B: 98.9% (91/92) versus 17.8% (8/45) on control; risk difference 81.1 percentage points (95% CI 69.8 to 92.5), risk ratio 5.56 (2.97–10.43); unadjusted two-proportion z-test p = <0.001.
• OnabotulinumtoxinA X Dose C: 98.0% (99/101) versus 17.8% (8/45) on control; risk difference 80.2 percentage points (95% CI 68.7 to 91.7), risk ratio 5.51 (2.94–10.34); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants With Achievement of None or Mild as Rated by Investigator Using the Clinician Glabellar Lines Scale.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • OnabotulinumtoxinA X Dose A: 90.0% (81/90) versus 6.7% (3/45) on control; risk difference 83.3 percentage points (95% CI 73.8 to 92.9), risk ratio 13.50 (4.51–40.37); unadjusted two-proportion z-test p = <0.001.
  • OnabotulinumtoxinA X Dose B: 93.5% (86/92) versus 6.7% (3/45) on control; risk difference 86.8 percentage points (95% CI 77.9 to 95.7), risk ratio 14.02 (4.69–41.89); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for OnabotulinumtoxinA X Dose A than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for OnabotulinumtoxinA X Dose B than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With Achievement of Improvement Per the Facial Lines Satisfaction Questionnaire Impact Domain, Among Subjects With Baseline Scores of 14 Points or Greater.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • OnabotulinumtoxinA X Dose A: 65.6% (59/90) versus 42.2% (19/45) on control; risk difference 23.3 percentage points (95% CI 5.9 to 40.8), risk ratio 1.55 (1.07–2.25); unadjusted two-proportion z-test p = 0.010.
  • OnabotulinumtoxinA X Dose B: 71.7% (66/92) versus 42.2% (19/45) on control; risk difference 29.5 percentage points (95% CI 12.4 to 46.6), risk ratio 1.70 (1.18–2.45); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for OnabotulinumtoxinA X Dose A than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for OnabotulinumtoxinA X Dose B than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With Achievement of Satisfaction With Treatment Per the Facial Line Satisfaction Questionnaire Item 5.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • OnabotulinumtoxinA X Dose A: 80.0% (72/90) versus 4.4% (2/45) on control; risk difference 75.6 percentage points (95% CI 65.3 to 85.8), risk ratio 18.00 (4.63–70.04); unadjusted two-proportion z-test p = <0.001.
  • OnabotulinumtoxinA X Dose B: 78.3% (72/92) versus 4.4% (2/45) on control; risk difference 73.8 percentage points (95% CI 63.5 to 84.2), risk ratio 17.61 (4.52–68.54); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for OnabotulinumtoxinA X Dose A than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for OnabotulinumtoxinA X Dose B than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes give additional views of the trial results: investigator-rated attainment of none or mild severity, a participant-reported impact-domain improvement among those with baseline scores of 14 points or greater, and satisfaction with treatment. Across these outcomes, the posted percentages generally show higher achievement in the active-dose groups than in placebo. The patterns complement the primary finding because they address related but distinct constructs, including a severity threshold and participant-reported experience.

These endpoints should not be treated as interchangeable with the primary responder definition. The none-or-mild outcome is a final severity category rather than the primary definition of at least a 1-grade improvement. The impact-domain outcome applies to a specified baseline-score subgroup. The treatment-satisfaction outcome uses a questionnaire item and has a different assessment timeframe from the primary endpoint. Differences in endpoint definition, eligible analysis population, and timing mean that one outcome cannot be used as a direct substitute for another.

The registry posts unadjusted comparisons for the secondary outcomes, and the record does not report additional analysis entries. When several outcomes and dose-versus-placebo comparisons are evaluated, unadjusted p-values carry less weight because they do not account for the number of statistical tests. This does not erase the descriptive pattern, but it means the inferential evidence from individual secondary p-values should be interpreted cautiously. The registry record does not report whether the trial's original plan designated a hierarchy, controlled a family-wise error rate, or treated these outcomes as exploratory.

Considering the secondary outcomes alongside the primary endpoint can show whether findings point in a broadly consistent direction across measures. It cannot, without a reported multiplicity strategy and complete analysis plan, establish that every outcome is independently confirmatory. The secondary results add context, while the primary endpoint remains the outcome explicitly identified as primary in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With Achievement of None or Mild as Rated by Investigator Using the Clinician Glabellar Lines Scale.
• Percentage of Participants With Achievement of Improvement Per the Facial Lines Satisfaction Questionnaire Impact Domain, Among Subjects With Baseline Scores of 14 Points or Greater.
• Percentage of Participants With Achievement of Satisfaction With Treatment Per the Facial Line Satisfaction Questionnaire Item 5.

9. Statistical Interpretation

10. Statistical Methods Explained

What does a responder percentage describe?

A responder percentage is the share of participants meeting a defined outcome threshold. In this study, the threshold is at least a 1-grade improvement from baseline on the Clinician Glabellar Lines Scale, as rated by an investigator. The percentage does not indicate how much each responder improved beyond that threshold. Nor does it show the distribution of scale changes among participants who did not meet the threshold. It is a concise summary of how often the specified event occurred in each group.

How should the risk difference be read?

A risk difference compares the event rates in two groups by subtracting one rate from the other. Here, the posted comparisons are active dose versus placebo. A positive estimate means the observed responder rate was higher in the named dose group than in the placebo group. The reported estimates are 0.778 for Dose A, 0.811 for Dose B, and 0.802 for Dose C. The registry also gives a 95% confidence interval for each estimate. These values are on the risk-difference scale and are not the odds ratio or relative risk, which are other ways of expressing a comparison.

Each posted p-value for the primary risk-difference comparisons is unadjusted and reported as < 0.001. A p-value describes how incompatible the observed data are with a specified null hypothesis under the test assumptions; it is not the probability that the null hypothesis is true, nor a measure of the size or importance of an effect. The registry record does not identify the full test procedure or state whether a multiplicity adjustment was part of the trial's analysis plan.

What does the confidence interval add?

A confidence interval communicates uncertainty around an estimate. Its endpoints mark a range of values compatible with the data under the method used to construct the interval. It is not a guarantee that the true value lies in that particular interval, and it does not represent the range of individual participants' outcomes. Wider intervals indicate less precision than narrower intervals, other things being equal. The registry states that the primary responder-rate confidence intervals use a normal approximation.

How were primary responder rates handled?

The primary population is labeled Multiple Imputation - Intent-to-Treat. The registry describes the estimated responder as the average number of responders across 5 imputed datasets. Multiple imputation is a general approach to missing data that fills in missing values repeatedly using a statistical model, then combines information across completed datasets. The intention-to-treat principle generally aims to analyze participants according to their randomized group. The registry does not state the imputation model, the amount or pattern of missing primary-outcome data, or the assumptions used for missingness. It therefore cannot establish from the posted description how sensitive the result is to alternative missing-data assumptions.

Why can over-dispersion matter?

Over-dispersion is a general statistical issue in which observed variability is greater than a model expects. It can make standard errors too small if the analysis assumes less variability than is present, which can in turn make confidence intervals too narrow and p-values too small. The primary endpoint is binary, so the relevant concern would be whether the chosen model or approximation adequately represents the variability of responder outcomes. The registry describes a normal approximation for the confidence interval, but does not report a diagnostic assessment of over-dispersion or details that would establish how this issue was evaluated. This is a general explanation, not a claim that over-dispersion occurred in this trial.

What can and cannot be inferred from the posted comparisons?

The posted primary comparisons address each active dose against placebo. They do not constitute head-to-head tests between Dose A, Dose B, and Dose C. A pattern of similar observed rates is descriptive and does not establish equivalence or non-inferiority. Such conclusions require a prespecified design and analysis approach, which are not reported in the registry record. The posted p-values are described as unadjusted. When several outcomes or comparisons are examined, the chance of at least one apparently strong result can increase; multiplicity procedures are designed to address that general issue. Whether any such procedure was planned or used is not reported in the registry record.

Finally, statistical significance and precision are distinct. A small p-value does not by itself convey how uncertain the effect estimate is, while a confidence interval describes a range of uncertainty without replacing the trial's design or analysis plan. The registry provides estimates and intervals for the posted outcomes, but not the full protocol, statistical analysis plan, imputation diagnostics, or additional reported analysis entries. Interpretation is therefore anchored to the stated endpoint definitions, reported estimates, and explicit analysis descriptions.

11. Confidence Intervals and Precision

The primary responder percentages are accompanied by 95% confidence intervals. For placebo, the interval is 6.6 to 28.9; for Dose A it is 91.3 to 99.8; for Dose B it is 96.8 to 100.0; and for Dose C it is 95.3 to 100.0. These intervals describe uncertainty in the estimated responder rate for each group, not variation among individual participants. The estimates for the dose groups are near the upper end of the percentage scale, and their intervals extend to 100.0.

For the comparisons with placebo, the risk-difference confidence intervals are 0.658 to 0.897 for Dose A, 0.698 to 0.925 for Dose B, and 0.688 to 0.917 for Dose C. Each interval is above zero. These comparison intervals are more directly relevant to uncertainty in the contrast than comparing the separate group-level intervals. They still do not represent dose-to-dose comparisons.

Precision depends on the amount of information in the data and the variability of the outcome. General statistical interpretation: a confidence interval is a range generated by a method with a specified long-run coverage property, when that method's assumptions hold. The registry states that primary responder-rate intervals use a normal approximation and that the responder estimate averages across 5 imputed datasets. It does not provide diagnostic information about the approximation or details of the imputation model. The intervals should therefore be read in conjunction with these limited method details, rather than as a complete account of every source of uncertainty.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations give participants per arm for binary outcomes; they are not totals across all groups and are not total-event counts. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The original trial's own sample-size assumptions and justification are not reported in the registry record.

The 80% power column describes the planned number of participants per arm under the stated assumptions for an 80% chance of detecting the chosen effect if that effect is the true one. The 90% power column gives the corresponding number for a 90% chance. These are design-planning quantities, not guarantees about the result of a future study. The illustrations are based on the observed effect in this trial, so they depend on an effect estimate that may differ from the effect in another study.

Rows planning for a smaller fraction of the observed effect require more participants per arm in the listed illustrations. This is a general feature of statistical planning: smaller differences are harder to distinguish from random variation, so more information is typically needed. The displayed estimates are illustrative rather than a reconstruction of the trial's original enrollment plan. They are not observed power; observed power is not an appropriate substitute for interpreting the estimates and confidence intervals from the completed trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.178; treatment proportion p₁ = 0.956; average p̄ = 0.567.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7008 = 1.3735.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4343 = 0.3655.
4. n = (1.3735 + 0.3655)² / (0.7778)² = 5.0, rounded up to 5 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.177777777777778                          # control proportion
p1 <- 0.955555555555556                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(5100199)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 5 (80% power), 7 (90% power)
 75% of observed effect: n per arm = 11 (80% power), 14 (90% power)
 50% of observed effect: n per arm = 24 (80% power), 31 (90% power)
power.prop.test: 5 
Simulated power at n = 5 per arm: 0.840 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, comparisons, timepoints, or analysis populations. Even if each test is considered at its own significance threshold, conducting many tests can increase the chance that at least one result appears statistically notable by chance. Adjustments or prespecified testing hierarchies can address this issue, but they may affect how p-values and confidence intervals are interpreted.

This study has a primary endpoint and several secondary outcomes, and the posted comparisons include active dose groups against placebo. The p-values in the posted comparisons are unadjusted. The registry record does not report whether multiplicity was addressed in the original statistical analysis plan, whether a testing sequence was prespecified, or whether any adjusted estimates or p-values were calculated. As a result, the unadjusted p-values should not be read as if they necessarily controlled the error rate across all outcomes and comparisons.

The primary endpoint population is described as Multiple Imputation - Intent-to-Treat, with responder estimates averaged across 5 imputed datasets. The record states that confidence intervals for responder rates use a normal approximation. It does not report the imputation model, the amount of missing data, reasons for missingness, sensitivity analyses, or the missing-data assumptions. The handling of missing data for the secondary endpoints is not reported in the registry record. For the satisfaction impact-domain outcome, the stated population is limited to subjects with baseline scores of 14 points or greater.

The registry record does not report interim analyses, stopping boundaries, a detailed statistical analysis plan, or further reported analysis entries. Their absence from the record does not establish what was or was not included in documents outside the record; it means those methods cannot be evaluated from the posted descriptions. These omissions limit assessment of how analysis choices, missing data, or multiple testing may affect the strength of the inferential conclusions.

15. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: invasive ductal breast carcinoma (2.2%), bundle branch block right (1.1%), amniotic cavity infection (1.0%), diabetes mellitus inadequate control (1.0%), intracranial aneurysm (1.0%).

The posted serious adverse event counts are 1 participant among 45 at risk in placebo, 1 among 90 in Dose A, 0 among 91 in Dose B, and 2 among 99 in Dose C. The record lists 0 deaths in each group. These counts describe the serious adverse events recorded for the respective groups; they do not establish that an event was caused by the assigned injection.

The registry also lists non-serious adverse-event counts of 11 among 45 in placebo, 15 among 90 in Dose A, 14 among 91 in Dose B, and 22 among 99 in Dose C. Counts should be read with the group sizes in mind, and the posted summaries do not provide enough detail to assess event timing, duration, severity beyond the serious/non-serious distinction, or attribution. The registry lists serious-event terms including invasive ductal breast carcinoma, bundle branch block right, amniotic cavity infection, diabetes mellitus inadequate control, intracranial aneurysm, and abortion spontaneous. The record's summary does not provide enough context to infer causes or compare those terms by treatment group.

These safety counts are descriptive. They do not rule out uncommon or later events, and they are not a substitute for the full safety reporting or clinical interpretation.

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

The posted results describe a randomized comparison of placebo with three OnabotulinumtoxinA X dose groups in adults with moderate to severe glabellar lines. For the primary endpoint, a high percentage of participants in each active-dose group met the investigator-rated improvement threshold from Day 1 to Day 30, while the placebo group's reported percentage was lower. The risk-difference estimates and their confidence intervals describe the size and precision of the posted comparisons with placebo.

These results do not establish that one active dose is better than another. The registry record posts dose-versus-placebo comparisons but does not report head-to-head tests or an equivalence or non-inferiority analysis. Similar observed percentages are not proof that the doses have the same effect. The primary endpoint also captures whether a specified threshold was reached, not the full range of individual changes or the duration of any response beyond the stated timeframe.

The results do not by themselves resolve the impact of missing data or multiple testing. Primary response estimates use multiple imputation, but the model and missingness assumptions are not reported. The comparisons' p-values are unadjusted, and the record does not state whether a multiplicity strategy was used in the original analysis. Confidence intervals and p-values should be interpreted with these limitations in view.

The safety summaries report serious and non-serious adverse-event counts and deaths by group, but they do not establish whether an event was caused by treatment or characterize all aspects of event timing and clinical course. The study results are limited to the recorded participants, outcomes, groups, and observation timeframes. The registry record does not report longer-term outcomes or enough information to infer results in populations beyond the studied adults with moderate to severe glabellar lines.

In statistical terms, the posted data support a description of the observed outcome patterns and uncertainty for the stated analyses. They do not independently provide a complete account of the trial's protocol, analysis plan, or all sources of uncertainty.

17. Why This Trial Matters Statistically

This trial illustrates how outcome definition shapes interpretation. The primary endpoint is not simply a change in a scale score; it is the proportion meeting a threshold of at least a 1-grade improvement on an investigator-rated measure. That makes the reported percentages accessible, while also leaving out the amount of change beyond the threshold. Reading the endpoint definition alongside the percentages helps keep the result tied to what was actually measured.

The study also illustrates the value of distinguishing group-level response rates from between-group contrasts. A higher rate in an active-dose group is descriptive; the risk difference and its confidence interval quantify the comparison with placebo. The posted intervals convey uncertainty in those contrasts. The comparisons do not test the active doses against one another, so the similarity of their observed response percentages should not be overinterpreted.

Multiple outcomes and comparisons raise a separate issue from effect size and precision. The posted p-values are unadjusted, and the registry record does not report how multiplicity was handled in the original plan. This matters because a collection of individual p-values can convey more apparent certainty than a prespecified inferential strategy supports. The record also states that multiple imputation was used for the primary population, while leaving important details of missing-data handling unreported.

Finally, the example shows why outcome results and safety summaries should be read as different evidence streams. Responder percentages describe the primary efficacy endpoint; adverse-event counts describe reported safety events. Neither alone is a complete account of the study. Together with explicit attention to their definitions, populations, timeframes, and uncertainty, they offer a more disciplined statistical reading of a clinical trial registry record.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record leaves several trial-specific details unavailable. It does not report the amounts represented by Dose A, Dose B, or Dose C, the allocation ratio, the randomization procedure, or detailed participant eligibility and baseline characteristics. The record identifies the study as multicenter and lists quadruple masking, but does not identify the masked roles or explain the relationship between that description and the double-blind wording in the official title.

For the primary analysis, the record states that multiple imputation was used and that the estimate averaged responders across 5 imputed datasets. It does not describe the imputation model, missing-data amount or patterns, or sensitivity analyses. The method for handling missing data in the secondary outcomes is not reported in the registry record. These gaps make it difficult to judge how robust the reported estimates are to alternative assumptions.

The primary comparisons are posted with unadjusted p-values. Whether multiplicity was addressed in the original analysis plan is not reported. The registry record also does not include the full statistical analysis plan, the original sample-size justification, interim-analysis information, or dose-to-dose inferential comparisons. The planning illustrations based on observed effects do not fill in those missing design details.

Finally, the primary outcome is assessed over Day 1 to Day 30, while one secondary satisfaction outcome extends to Day 60. The registry record does not report longer-term outcome results. The posted adverse-event summary provides counts but not event-level timing, course, or attribution. These limitations constrain what can be concluded from the registry summaries without implying that unreported details were absent from the full trial documentation.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study to the Assess the Change in Condition and Adverse Events of OnabotulinumtoxinA X Injection in Adult Participants With Glabellar Lines — NCT05100199.
• Registry record last updated 2025-09-09; status last verified 2025-08.
• Results first posted 2025-09-09.
• 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.

22. Record Summary

NCT05100199 is a completed Phase 2 randomized, placebo-controlled parallel-group study of OnabotulinumtoxinA X in adults with moderate to severe glabellar lines. The registry lists 328 participants enrolled, four groups—placebo and three dose groups—and quadruple masking. The listed study start date is 2021-10-06, and primary completion is dated 2022-12-02.

The primary outcome is the percentage with at least a 1-grade investigator-rated improvement from baseline on the Clinician Glabellar Lines Scale between Day 1 and Day 30. The registry describes a Multiple Imputation - Intent-to-Treat population and normal-approximation confidence intervals. Secondary outcomes cover severity, satisfaction-questionnaire measures, and treatment satisfaction. Posted primary comparisons are dose versus placebo and have unadjusted p-values.

The record does not report the original sample-size justification, full analysis plan, multiplicity strategy, or detailed missing-data methods. Safety summaries list serious and non-serious adverse-event counts by group and 0 deaths in each group.