TEOSYAL® RHA Global Action, TEOSYAL® RHA Deep Lines, and Juvéderm® Ultra XC for the Correction of Nasolabial Folds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for TEOSYAL® RHA Global Action, TEOSYAL® RHA Deep Lines, and Juvéderm® Ultra XC for the Correction of Nasolabial Folds (NCT02195427), a randomized na study. The primary outcome is Non-inferiority of the Delta of TEOSYAL® RHA GA and TEOSYAL® RHA DL Versus Juvéderm® Ultra XC for the Correction of Moderate to Severe NLFs Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the Blinded Live Evaluator (BLE)..

2. Clinical Question

3. Trial Design

The registry record describes a randomized, double-blinded, prospective, multicenter study and lists its design model as parallel. It also describes the study in its official title as within-subject, and the arm descriptions specify split-face injections: a TEOSYAL® product in one nasolabial fold and Juvéderm® Ultra XC in the contralateral fold. These descriptions point to paired comparisons within participants, while the recorded model is parallel. The registry does not explain this difference in design labels.

The study evaluated two comparisons: TEOSYAL® RHA Global Action against Juvéderm® Ultra XC and TEOSYAL® RHA Deep Lines against Juvéderm® Ultra XC. The arm descriptions list n=75 for each comparison. The primary outcome results list 67 participants for each Global Action comparison and 62 for each Deep Lines comparison. These figures refer to the outcome entries as recorded; the registry record does not explain the difference between the arm-description counts and the primary outcome counts.

Both products were injected into the mid-dermis to deep-dermis. The arm descriptions allow up to 3.0 mL per nasolabial fold at treatment and a touch-up at 2 weeks, also up to 3.0 mL per fold. The record lists assessment of the primary endpoint at baseline and 24 weeks after the last treatment. It also lists secondary assessments extending to W64 for some WSRS outcomes, alongside treatment-response, pain, aesthetic-improvement, and safety assessments.

The study status is completed. The registry lists its start as 2014-06 and primary completion as 2015-03. The phase is listed as NA. The registry record does not report the randomization procedure, the details of masking, or how the within-participant structure was handled in the statistical analysis.

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: One subject randomized to the RHA GA/J withdrew consent prior to receiving initial treatment reducing the population for this cohort to n=73.

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 Non-inferiority of the Delta of TEOSYAL® RHA GA and TEOSYAL® RHA DL Versus Juvéderm® Ultra XC for the Correction of Moderate to Severe NLFs Based on the Wrinkle Severity Rating Scale (WSRS) Score Assessed by the Blinded Live Evaluator (BLE)., measured over Baseline and 24 weeks after last treatment.

The primary endpoint is the mean change in WSRS score from baseline to 24 weeks after the last treatment, assessed by a Blinded Live Evaluator. The WSRS is described as a validated 5-point scale for wrinkle severity, ranging from 1, “absent,” to 5, “extreme.” A change in score therefore tracks change in the evaluator’s rating of fold severity over time. The posted mean changes are negative, consistent with movement toward a lower severity score on this scale.

The study frames the primary objective as non-inferiority: whether each TEOSYAL® product’s change in WSRS score is not unacceptably worse than that of Juvéderm® Ultra XC. Non-inferiority is a question about a prespecified acceptable margin, not merely whether two estimates look similar. That margin is not reported in the registry record, so the reported estimates and confidence intervals do not provide enough information to verify the decision rule.

Using a blinded evaluator can reduce the risk that knowledge of treatment assignment influences an assessment. The record identifies the evaluator as blinded, but does not provide further details about how assessments were conducted. In a split-face comparison, the same participant’s two folds can provide a naturally paired contrast, potentially accounting for participant-level characteristics shared by both sides. The registry record does not report whether the primary analysis used this pairing or how it addressed repeated measurements.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

A mean change describes the average movement in a measurement from its starting value to a later assessment. Here, the measurement is the WSRS score assessed by a Blinded Live Evaluator, and the primary timeframe is baseline to 24 weeks after the last treatment. Because the WSRS scale runs from 1, “absent,” to 5, “extreme,” a negative change corresponds to a lower average severity rating. A group mean does not describe the full distribution of individual outcomes: participants may have had different starting scores and different changes.

The posted primary outcome gives mean changes for each product group and then reports mean differences in final values for the two comparisons. The registry does not explain why the comparison parameter is described as a difference in final values while the endpoint title refers to the delta. Nor does it give the analysis details needed to determine how baseline values or the within-participant split-face design entered the model. These details are not reported in the registry record.

How should a confidence interval be read?

A confidence interval expresses uncertainty around an estimate under a specified statistical procedure. It gives a range of values compatible with the observed data and analysis assumptions; it is not a guarantee that the true effect lies within that particular interval. The primary comparisons use 97.5% confidence intervals. Both reported intervals include zero, so the posted intervals do not rule out a zero mean difference under the analyses represented by those results. They also allow differences in either direction within their bounds.

For a non-inferiority question, the key reference is the non-inferiority margin: the largest difference considered acceptable under the study’s plan. The confidence interval must be assessed against that margin in the direction specified by the protocol. Similar point estimates or an interval that includes zero are not sufficient to determine non-inferiority. The margin and the analysis rule are not reported in the registry record, so the non-inferiority result cannot be independently assessed from the posted summary alone.

Why does the split-face description matter?

General statistical explanation: when two treatments are compared on opposite sides of the same participant, observations from the two sides are paired. Participant characteristics shared across sides may make the two measurements more alike than measurements from unrelated participants. A paired analysis uses that relationship; treating paired observations as independent can misstate uncertainty. The registry describes split-face injections but lists a parallel model and does not state how the pairing was represented in the primary analysis. The statistical method is not reported in the registry record.

Double masking and a blinded live evaluator are design features intended to reduce the influence of treatment knowledge on assessments. They do not, by themselves, settle issues such as missing observations, analysis populations, or the handling of paired measurements. The record does not give enough detail to evaluate those aspects.

What do the secondary recalculations mean?

Some secondary comparisons are recalculated from the posted summary statistics. These are simple, unadjusted comparisons, not the study’s reported analyses. For continuous outcomes such as volume, a mean difference expresses the difference between group averages. For a participant count, a risk difference expresses a difference in the observed proportions. Confidence intervals convey uncertainty around these estimates. The recalculations do not account for unreported design features or adjustments, and their p values are unadjusted.

Planning illustrations based on an observed secondary effect can show how a sample size might vary under stated assumptions. They are not estimates of the trial’s power after the fact, and they do not establish that an effect is real. The registry’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect defined as a fraction of the observed effect. Such illustrations are sensitive to the observed effect; estimates close to zero can imply very large planning requirements. They should not be mistaken for the original design’s sample-size justification, which is not reported in the registry record.

General statistical explanation: over-dispersion occurs when the observed variability is greater than a model’s assumptions allow. In that situation, standard errors may be too small and intervals too narrow if the extra variability is ignored. The registry record does not identify an over-dispersion issue or report a model that would allow its assessment. This concept is relevant generally, but no claim about over-dispersion in this study can be made from the posted information.

Why are unadjusted results limited?

When a study examines multiple endpoints, timepoints, evaluators, and treatment comparisons, the chance of finding at least one apparently notable result can increase if each is tested independently without adjustment. An adjustment or prespecified hierarchy can address this issue, but the registry does not report a multiplicity plan. Unadjusted secondary p values should therefore be treated as exploratory rather than as stand-alone confirmation. The registry also does not report a full statistical analysis plan, so the intended handling of endpoints and comparisons cannot be reconstructed from the outcome summaries alone.

10. Analyses Reported by the Sponsor

The registry reports sponsor analyses for the primary non-inferiority comparisons. For Global Action versus Juvéderm® Ultra XC, the reported mean difference in final values is -0.03, with a 97.5% confidence interval from -0.17 to 0.11. For Deep Lines versus Juvéderm® Ultra XC, it is -0.10, with a 97.5% confidence interval from -0.25 to 0.06. No primary p values or non-inferiority margin are reported in the registry record.

The simple recalculations elsewhere in the posted results concern secondary outcomes and are not substitutes for the sponsor’s primary analysis. They use posted summary statistics and do not reproduce an analysis that accounts for any paired structure, adjustments, or other methods not described in the record. The registry does not flag a discrepancy between the reported and recalculated results. For interpretation of the primary endpoint, the sponsor’s reported analysis is the relevant result; the missing margin and analysis details still limit an independent assessment of the non-inferiority claim.

The closeness of the primary point estimates should not be treated as proof that the products are equivalent. A non-inferiority conclusion depends on comparing an interval with a prespecified margin, not simply on a small mean difference. As that margin is not reported in the registry record, the posted primary results allow the estimates and their uncertainty to be described, but do not show whether the formal non-inferiority criterion was satisfied.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary non-inferiority outcome and a range of secondary outcomes, including assessments at different timepoints and by different evaluators. It does not report how the multiple comparisons were prioritized or whether any adjustment for multiplicity was planned. When many outcomes are examined, nominal statistical findings can arise by chance even when there is no underlying difference. This is why an analysis plan may specify a hierarchy or adjustment. Without a reported plan, the secondary results are best treated as descriptive or exploratory rather than as a set of independent confirmatory claims.

Missing-data handling is not reported in the registry record. The primary outcome entries list n=67 for each Global Action comparison and n=62 for each Deep Lines comparison, while the arm descriptions list n=75 per comparison. The record does not explain why the outcome counts differ, whether observations were excluded, how missing values were handled, or whether any sensitivity analyses were conducted. The number of participants included in a particular outcome entry is not necessarily the number randomized or the number with complete follow-up, and those distinctions are not fully.

The analysis populations are also not reported in the registry record. It does not identify whether the primary analysis used an intention-to-treat population, a per-protocol population, or another defined set. That information matters in non-inferiority studies because different analysis populations can affect interpretation, particularly if exclusions or non-adherence influence the contrast.

The record gives randomization and double masking as design features, but does not provide the sequence-generation method, allocation concealment details, or the statistical treatment of the split-face pairing. It also does not report interim analyses, a sample-size justification, or a complete statistical analysis plan. These omissions limit the ability to assess prespecification, robustness, and the handling of multiple endpoints. They do not establish that any particular method was or was not used; those methods are simply not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastric ulcer (1.3%), gatric ulcer perforation (1.3%).

The registry reports serious adverse events for the four product groups. The Global Action group and its Juvéderm® comparator each have 2 serious adverse events among 75 at risk; the Deep Lines group and its Juvéderm® comparator each have 0 among 75 at risk. The record lists Gastric Ulcer and Gatric Ulcer Perforation among the top serious-event terms, each at 1.3%. The registry does not provide enough detail in these summary figures to establish whether the two terms refer to separate participants or events, or to assess timing and relatedness.

Other adverse events are reported among those at risk for non-serious events: 39 among 72 for Global Action, 36 among 72 for its comparator, 30 among 75 for Deep Lines, and 31 among 75 for its comparator. These figures describe the registry’s recorded event counts, not a causal comparison. The record does not report deaths; death information is not reported in the registry record.

Adverse-event summaries need context about definitions, duration of follow-up, severity, relatedness, and how events were collected. Although the registry lists safety assessments, those details are not fully available in the posted summaries. The figures should therefore be read as descriptive safety reporting for this study, not as proof that a product caused or prevented an event.

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

The posted results describe average changes in evaluator-rated wrinkle severity for two TEOSYAL® products and their Juvéderm® Ultra XC comparators. The primary mean differences are close to zero, and the reported 97.5% confidence intervals include zero. This is a description of the estimated comparisons and their uncertainty, not evidence that all participants experienced the same outcome or that the products are interchangeable.

The study’s stated primary objective is non-inferiority. To determine whether that objective was met, the interval must be assessed against the prespecified non-inferiority margin using the planned analysis. The margin is not reported in the registry record, and the analysis details are limited. The registry results therefore do not allow an independent reader to verify the formal non-inferiority decision from the posted summary alone.

The results also do not answer every question a reader might ask about the products. The record includes selected timepoints, evaluators, and secondary outcomes, but does not provide a full account of participant-level results, missing-data handling, or all analysis methods. It does not establish how well findings would apply to populations or settings beyond the study as described. General statistical explanation: a trial estimate is conditional on its population, measures, follow-up, and analysis; statistical uncertainty and design limitations remain relevant even when a point estimate appears small.

These registry results are not a basis for personal treatment decisions. They report clinical-trial measurements and safety summaries; they do not constitute individualized medical advice. The appropriate statistical conclusion is bounded: the record presents two primary mean-difference estimates with uncertainty, but leaves important details needed to judge the non-inferiority criterion unreported.

14. Why This Trial Matters Statistically

This study is statistically notable because its arm descriptions use a split-face design, while the registry’s design-model field says parallel. In general, within-participant comparisons can control for characteristics shared by a participant’s two sides, but they require an analysis that respects the pairing. The registry does not state how that structure was handled. This makes the distinction between study description and analysis method important when interpreting the reported uncertainty.

The primary objective is non-inferiority, a framework that depends on a prespecified margin. A small estimated difference and a confidence interval including zero do not, on their own, demonstrate non-inferiority. The margin is not reported in the registry record. This illustrates why interpreting a result requires more than looking at whether a point estimate is close to zero or whether an interval crosses zero: the inferential question and decision boundary must be known.

The record also presents multiple product comparisons and a broad set of secondary outcomes spanning evaluators, timepoints, and outcome types. A multiplicity plan would help distinguish confirmatory findings from exploratory patterns, but that plan is not reported. The secondary summaries can still be informative descriptively, though they should not be treated as equivalent evidence to a clearly specified primary analysis.

Finally, the different participant counts in the arm descriptions and primary outcome entries emphasize the role of analysis populations and missing-data reporting. Without reasons for the differences or a description of missing-data methods, precision and possible selection effects are harder to assess. Together, these features make the trial a useful example of how design labels, analysis choices, decision margins, and reporting completeness shape interpretation—not just the numerical estimate.

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.

Several limitations specific to this study arise from gaps in the registry record. Although the official title and arm descriptions describe a within-subject, split-face comparison, the model is listed as parallel. The record does not explain this difference or report the statistical handling of paired folds. That omission makes it difficult to confirm that the reported standard uncertainty reflects the design described in the arms.

The primary endpoint is framed as non-inferiority, but the margin and the decision rule are not reported. Primary p values are also not reported. The sponsor’s mean differences and confidence intervals can be described, but the formal non-inferiority conclusion cannot be independently checked using the registry summary alone.

The primary outcome entries list fewer participants than the arm descriptions. Reasons for that difference, the analysis populations, the follow-up completeness, and missing-data methods are not reported in the registry record. These unknowns matter because the included observations and their treatment can affect both estimated effects and uncertainty.

The registry also does not report the randomization procedure, allocation concealment, detailed masking procedures, sample-size justification, interim analyses, or a full statistical analysis plan. A multiplicity strategy for the several secondary outcomes is not reported either. The available secondary recalculations are unadjusted and do not reproduce potentially more complex paired or adjusted analyses. These limitations do not show that appropriate methods were absent; they describe what cannot be assessed from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: TEOSYAL® RHA Global Action, TEOSYAL® RHA Deep Lines, and Juvéderm® Ultra XC for the Correction of Nasolabial Folds — NCT02195427.
• Registry record last updated 2018-04-25; status last verified 2018-03.
• Results first posted 2018-03-26.
• 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

NCT02195427 is a completed randomized, double-blinded study sponsored by Teoxane SA. It evaluated TEOSYAL® RHA Global Action and TEOSYAL® RHA Deep Lines against Juvéderm® Ultra XC for moderate to severe nasolabial folds. The registry lists enrollment of 148 and describes split-face injections in the arm descriptions, while the design model is listed as parallel.

The primary endpoint was mean WSRS change from baseline to 24 weeks after the last treatment, assessed by a Blinded Live Evaluator. The registry reports mean differences of -0.03 for Global Action versus its comparator and -0.10 for Deep Lines versus its comparator, each with a 97.5% confidence interval. The non-inferiority margin is not reported in the registry record, limiting independent assessment of the primary objective.

Secondary outcomes include treatment volume, touch-up, safety, pain, WSRS assessments, and aesthetic-improvement ratings. The registry does not report key analysis details, including missing-data methods, analysis populations, pairing methods, or a multiplicity plan. These omissions warrant cautious interpretation of the posted estimates.