Study to Evaluate the Effectiveness, Safety and Long Term Safety of Saypha® FILLER Lidocaine for Lip Augmentation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Effectiveness, Safety and Long Term Safety of Saypha® FILLER Lidocaine for Lip Augmentation (NCT04917588), a randomized na study. The primary outcome is Responder Rate in Lip Volume Improvement.

2. Clinical Question

The clinical question is about the responder rate after lip augmentation, with the manufacturing facility distinguishing the randomized groups. The registry record identifies a prospective, open-label, multicentre, randomized study and describes bilateral treatment in both groups. It does not report the Week 6 responder counts, group-specific rates, or a statistical comparison between groups. Therefore, the record does not establish whether the observed responder rates differed or how precisely any difference was estimated.

3. Trial Design

The registry record describes a prospective, open-label, multicentre, randomized, parallel-group study. It lists an enrollment of 114 and a completed status. The study began on 2020-07-28, and the primary completion date is 2020-12-14. The record lists the phase as NA. The sponsor is Croma-Pharma GmbH.

Both groups received Saypha® FILLER Lidocaine for bilateral lip augmentation. The distinction recorded between the groups is the facility where the product was manufactured: the Croma Pharma HQ Facility or the Croma Pharma C1 Facility. Each arm description specifies administration at Baseline (Day 0). Randomization is listed, but the method used to generate the allocation sequence, the allocation concealment process, and whether allocation was balanced are not reported in the registry record. Equal allocation appears only as an assumption for planning illustrations, not as a reported feature of the trial design.

The study was open-label, meaning masking is listed as none. The registry record does not describe whether outcome assessors were kept unaware of assignment; the primary endpoint is based on an investigator live assessment. The planned duration of follow-up beyond the primary endpoint, details of visits, and the operational procedures for handling treatment or assessment deviations are not reported in the registry record.

The primary endpoint is assessed at Week 6. Additional listed outcomes include responder assessments by an independent photographic reviewer, improvement assessed with GAIS by investigators and subjects, satisfaction measured using Face-Q questionnaires, pain measured with an 11-point Numeric Pain Rating Scale, and aesthetic effect. The registry record lists no result analyses. Consequently, the design and endpoint definitions can be described, but the posted record does not provide numerical efficacy results for interpretation.

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: Population considered for this analysis is the Full Analysis Set (FAS) which comprises all subjects who received at least 1 administration of the IMD and who had at least 1 post-treatment evaluation of the LFS. Individual LFS grades per visit are calculated separately for the upper and the lower lip.

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: Population considered for this analysis is the Full Analysis Set (FAS) which comprises all subjects who received at least 1 administration of the IMD and who had at least 1 post-treatment evaluation of the LFS.

6. Primary Endpoint

The registry lists the primary outcome as Responder Rate in Lip Volume Improvement, measured over Week 6.

The primary endpoint is the responder rate in lip volume improvement at Week 6. A responder is a participant whose Lip Fullness Scale assessment improves by at least 1 point from baseline, according to the investigator’s live assessment. The registry describes the Lip Fullness Scale as a validated 5-point rating scale for lip volume deficiency, ranging from Grade 1, minimal volume, to Grade 5, very significant volume. Higher grades represent greater lip volume.

A responder definition turns a scale change into a clinically interpretable count: the number of participants meeting the specified improvement threshold can be related to the number in the analysis population. The endpoint therefore asks how many participants reached a prespecified degree of change, rather than reporting only an average scale score. The registry record identifies the Full Analysis Set as the population for this analysis: subjects who received at least 1 administration and had at least 1 post-treatment Lip Fullness Scale evaluation.

The registry does not report the number of responders, the denominators used for the Week 6 calculation, or an estimated comparison between the randomized groups. It also does not provide the baseline and follow-up scale distributions. Without those results, the endpoint’s observed rate and the precision of a group comparison cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Outcome and analysis population. The primary outcome is binary: a participant either meets the responder definition or does not. The registry defines response as an improvement of at least 1 point from baseline on the investigator’s live Lip Fullness Scale assessment at Week 6. For a binary outcome, a responder rate is the proportion of participants meeting the definition among those included in the analysis. The registry identifies the Full Analysis Set as subjects who received at least 1 administration and had at least 1 post-treatment evaluation of the scale. It does not provide the actual numerator or denominator for either group’s Week 6 analysis.

General statistical explanation: binary outcomes are often described using counts and proportions. A comparison between groups can be expressed using a difference or another effect measure, with uncertainty represented by a confidence interval. The choice of measure and analysis method should be specified in the statistical plan; that plan and an estimated comparison are not reported in the registry record. No new effect estimate can be derived from the enrollment count alone.

Randomization and masking. Randomized allocation can, in general, help make groups comparable with respect to measured and unmeasured baseline characteristics, on average. It does not guarantee exact balance in a particular trial. The record identifies randomized allocation and a parallel model, but does not report the sequence-generation method, concealment procedures, stratification factors, or actual allocation ratio. The safety counts show 57 participants at risk in each group for the listed safety summaries, but those counts do not establish the planned allocation method for all efficacy analyses. Masking is listed as none, so the study is open-label. The registry does not describe any masking of outcome assessors.

Precision and uncertainty. General statistical explanation: an estimate from a finite sample is subject to sampling variability. A confidence interval communicates the range of estimates that remain reasonably compatible with the observed data under the selected statistical approach. Its width is affected by the amount of information and the variability of the outcome. A p-value, if reported, would address compatibility with a specified null hypothesis under a model; it would not by itself show the size, direction, or importance of an effect. The registry record contains no primary confidence interval or p-value, so the precision of the comparison is unknown from the posted results.

Planning illustrations. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. They describe an effect to detect as a stated fraction of the observed effect. These are assumptions for planning illustrations, not evidence about the trial’s own design or its results. The registry record does not report the protocol’s sample-size justification, and the observed primary effect needed to interpret such an illustration is not reported. A planning sample size is not observed power: it does not tell readers the probability that the completed trial detected an effect, and it is not a substitute for the estimate and uncertainty from the actual data.

Over-dispersion and model choice. General statistical explanation: for some count outcomes, observed variability can exceed what a simple model assumes. This is called over-dispersion and can affect uncertainty estimates if ignored. The primary endpoint is recorded as a participant-level binary responder outcome, not a count of repeated events. The registry record does not describe a model for the primary comparison, so it is not possible to say whether a particular modelling approach, adjustment, or variance correction was used. The record also does not report covariate adjustment or sensitivity analyses.

Multiplicity. Several secondary outcomes are listed in addition to the primary endpoint. When many outcomes or comparisons are tested, the chance of at least one apparently unusual result can rise if each is interpreted as a separate confirmatory test. General statistical approaches can address this through prespecified testing sequences or adjustments, while exploratory analyses may instead be interpreted cautiously. The registry record does not report a multiplicity strategy, an analysis hierarchy, or results for the listed secondary outcomes. Therefore, no claim about error-rate control or confirmatory status can be made.

Interpretation of the available statistics. The posted safety counts are descriptive participant counts. They do not supply the missing efficacy estimates, and they should not be treated as tests of group differences. The primary endpoint’s direction is defined by higher Lip Fullness Scale grades representing greater lip volume, but the registry record does not provide the group results needed to describe the observed direction or magnitude. Statistical interpretation is therefore limited to the stated design, outcome definition, analysis population, and recorded safety counts.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary responder endpoint and several secondary outcomes: investigator live assessment, independent photographic review, investigator and subject GAIS assessments, Face-Q satisfaction measures, pain on an 11-point Numeric Pain Rating Scale, and aesthetic effect. It does not report a multiplicity strategy, such as a hierarchy for testing outcomes or an adjustment for multiple comparisons. Without such information, it is not possible to determine which comparisons were intended to support confirmatory claims or how the overall chance of false-positive findings was managed.

The record identifies the Full Analysis Set for the primary endpoint as subjects who received at least 1 administration and had at least 1 post-treatment Lip Fullness Scale evaluation. This definition gives some information about who could contribute to the primary analysis. However, the record does not report how missing Week 6 assessments were handled, whether participants with missing measurements were counted as nonresponders, whether imputation was used, or whether sensitivity analyses were conducted. Those details are not reported in the registry record.

The registry does not report the populations used for the secondary efficacy analyses, any per-protocol population, or the handling of protocol deviations. Although 114 participants were enrolled, the number included in each efficacy analysis and the number with available Week 6 outcome data are not reported. Thus, the extent and potential consequences of missing outcome data cannot be assessed. No numerical efficacy analyses are listed in the record, so neither multiplicity procedures nor missing-data assumptions can be checked against reported results.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: depression (1.8%).

The safety summaries report 57 participants at risk in each group. For serious adverse events, the HQ group has 0 affected participants and the C1 group has 1. For other adverse events, the respective counts are 35 and 32. Deaths are reported as 0 in each group. Depression is listed as the top serious adverse event term, at 1.8%.

These are descriptive counts of participants with events, not estimates of comparative risk or statistical tests. The registry record does not provide event-level details, timing, severity, duration, outcome, or an assessment of causal relationship. It also does not report a confidence interval or p-value for a safety comparison. The listed serious-event term does not identify a group in the registry record, so it should not be attributed to either arm based on these summaries alone.

Differences in raw counts should not be interpreted as proof that one group is safer or less safe. The counts do not describe repeated events per participant, and the record does not specify whether participants could contribute to more than one event category. These safety figures also do not provide evidence about the primary efficacy endpoint.

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

The registry record describes a randomized comparison of Saypha® FILLER Lidocaine manufactured at the HQ and C1 facilities, and it defines a Week 6 responder outcome based on investigator assessment of lip volume. Those details make the intended primary question identifiable: the proportion of participants in each group whose Lip Fullness Scale score improved by at least 1 point from baseline.

What the record does not report is the primary result. There are no group-specific responder counts or proportions, no estimated effect between groups, and no confidence interval or p-value. The clinical meaning, direction, magnitude, and precision of the observed primary outcome therefore cannot be established from the posted results. The absence of a reported result is not evidence that the groups were the same, nor evidence that they differed.

The same distinction applies to the listed secondary endpoints. Their names indicate what was intended to be assessed, but without numerical results, no interpretation of satisfaction, pain, aesthetic effect, or other responder assessments is possible. The recorded safety counts provide limited descriptive information and do not substitute for efficacy findings or establish causation.

General statistical context: an observed difference, if available, would need to be considered alongside its uncertainty, the endpoint definition, the analysis population, missing data, and any multiplicity approach. Statistical significance alone would not convey the size or relevance of an effect; conversely, a non-significant result would not by itself demonstrate equivalence. The registry record does not report an equivalence or non-inferiority framework, nor the information needed to evaluate either.

The appropriate reading is therefore narrow. The record documents a completed randomized study and its planned primary outcome, while leaving the primary efficacy findings unavailable. It supports description of the study question and the reported safety counts, but not a conclusion about comparative efficacy, precision, or a treatment effect.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a clear endpoint definition and a randomized design do not, by themselves, allow readers to assess a treatment comparison. The record states the primary outcome threshold, assessment scale, analysis population, and Week 6 timing. These features tell readers what a responder was intended to mean and which participants were considered for the primary analysis.

At the same time, the registry record lists no outcome analyses. Without responder counts and denominators, there is no estimate to interpret, and without an interval or other uncertainty measure, there is no way to assess precision. This is a useful distinction for clinical researchers: a registered outcome definition describes what investigators planned to measure, whereas a numerical result is needed to understand what was observed.

The study also illustrates why open-label status and assessor procedures matter to interpretation. The registry lists masking as none and identifies an investigator live assessment for the primary outcome. It does not describe assessor masking or the measurement procedures in further detail. These registry entries do not establish bias, but they identify design information readers would consider when evaluating a subjective scale-based endpoint.

Finally, the presence of several secondary outcomes makes the statistical handling of multiple questions relevant. The record does not report a testing hierarchy or multiplicity adjustment. When results are available, prespecification and transparent reporting help readers distinguish the primary analysis from additional exploratory comparisons. In this record, neither the outcome analyses nor the multiplicity approach is available, limiting what can be concluded statistically.

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 principal limitation for interpreting this trial from the registry record is the absence of efficacy results. The primary responder counts, group proportions, comparative effect, uncertainty estimates, and p-value are not reported. The record lists no result analyses, so the primary endpoint cannot be quantitatively evaluated.

The primary measure is an investigator live assessment on a 5-point Lip Fullness Scale. The record identifies the scale and response threshold, but does not report assessor training, procedures for standardizing ratings across centres, or whether assessors knew the assigned manufacturing facility. Masking is listed as none; further assessor-specific masking information is not reported in the registry record. Because the endpoint depends on a rating, these measurement details would be relevant to interpretation but cannot be assessed from the record.

Information about the sample-size justification, the protocol’s statistical analysis plan, allocation concealment, and the randomization method is not reported in the registry record. Nor does the record describe baseline comparability, adherence, protocol deviations, missing Week 6 assessments, imputation, or sensitivity analyses. Although a Full Analysis Set is defined for the primary endpoint, the number analyzed in each group and the completeness of endpoint data are not reported.

The record lists multiple secondary outcomes but does not provide their results, analysis populations, timeframes, or a multiplicity strategy. This limits assessment of the wider outcome profile and the risk of selective emphasis among multiple comparisons. Safety information is limited to aggregate counts; event details and causal assessments are not reported. These are limitations of what can be concluded from the registry record and do not, by themselves, establish how the full trial report may address them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate the Effectiveness, Safety and Long Term Safety of Saypha® FILLER Lidocaine for Lip Augmentation — NCT04917588.
• Registry record last updated 2025-03-14; status last verified 2022-05.
• Results first posted 2025-03-14.
• 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

NCT04917588 is a completed, randomized, open-label, multicentre, parallel-group study sponsored by Croma-Pharma GmbH. The registry record lists an enrollment of 114 and compares Saypha® FILLER Lidocaine manufactured at the Croma Pharma HQ and C1 facilities. Both arm descriptions specify bilateral lip augmentation administered at Baseline (Day 0).

The primary endpoint is the Week 6 responder rate, defined by an improvement of at least 1 point from baseline on the investigator-assessed Lip Fullness Scale. The primary analysis population is the Full Analysis Set, defined as subjects who received at least 1 administration and had at least 1 post-treatment scale evaluation. The registry record lists no result analyses and does not report primary efficacy estimates.

Safety summaries report 0 serious adverse event participants in the HQ group and 1 in the C1 group, with 35 and 32 participants, respectively, affected by other adverse events. Deaths are reported as 0 in each group. These figures are descriptive; further event details and comparative statistical analyses are not reported in the registry record.