CCH Treatment of Cellulite in the Presence of Dermal Laxity With Comparison Between Two (2) Different Injection Techniques: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CCH Treatment of Cellulite in the Presence of Dermal Laxity With Comparison Between Two (2) Different Injection Techniques (NCT04580303), a randomized phase 2 study. The primary outcome is Percentage of 1-Level Responders (+1 or Better Score) on the Investigator-Global Aesthetic Improvement Scale (I-GAIS) for Either Buttock or Either Thigh.

2. Clinical Question

3. Trial Design

NCT04580303 is a phase 2, multicenter, open-label, randomized, parallel-group, multiple-dose study. It enrolled 35 participants and is listed as completed. The registry gives a start date of 2020-10-01 and a primary completion date of 2021-08-30. The sponsor is Endo USA Inc., a Keenova Therapeutics Company.

The trial examined CCH injection techniques in adult females with cellulite and dermal laxity affecting the buttocks or thighs. The four listed treatment groups combine treatment area with injection technique: a uniform 0.1-mL 1-aliquot grid technique for buttocks or thighs, and a uniform 0.3-mL 2-aliquot grid technique for buttocks or thighs. The arm descriptions specify up to 1.68 mg of CCH per participant per treatment visit, with 0.84 mg in each treatment area. The number and timing of treatment visits are not reported in the registry record.

Randomization assigns participants to study groups by chance, but the registry record does not report the allocation ratio, the randomization procedure, or whether assignment was stratified. Masking is listed as none, so the study was open label. The record does not describe procedures to reduce the influence of knowledge of treatment assignment on investigator ratings.

The registry describes a parallel-group design, meaning that participants were assigned to a treatment group rather than being described as switching between techniques. The primary outcome is reported separately for buttock and thigh groups, and there is no combined estimate for the two techniques. No untreated comparison group is listed. This means the posted primary results describe observed response proportions within the active-treatment groups; they do not give a randomized comparison against no treatment.

The registry identifies the primary endpoint population as modified Intent-to-Treat (mITT): enrolled participants who received at least 1 injection of CCH and had at least 1 valid I-GAIS evaluation after injection. Details of additional analysis populations, protocol deviations, and the handling of participants outside this definition are not reported in the registry record.

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: Participants were randomized to receive treatment in either a uniform 0.1-milliliter (mL), 1-aliquot, grid injection technique or uniform 0.3-mL, 2-aliquot grid injection technique in a 1:1 ratio. Each participant had 2 treatment areas (each buttock or each thigh).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat (mITT) Population: All enrolled participants who received at least 1 injection of CCH and who had at least 1 valid I-GAIS evaluation after the injection of CCH.

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: Safety Population: All enrolled participants who received at least 1 injection of CCH. Participants who received injection in the buttock or thigh are combined for each injection technique.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of 1-Level Responders (+1 or Better Score) on the Investigator-Global Aesthetic Improvement Scale (I-GAIS) for Either Buttock or Either Thigh, measured over Day 180.

The primary endpoint is the percentage of participants who were 1-level responders on the Investigator-Global Aesthetic Improvement Scale (I-GAIS) at Day 180. The scale is a 7-point investigator rating of overall aesthetic change compared with pretreatment. Its levels run from Very Much Worse (-3), Much Worse (-2), Worse (-1), and No Change (0), to Improved (+1), Much Improved (+2), and Very Much Improved (+3).

A participant counts as a responder for a treatment area if the score is +1, +2, or +3. The primary outcome is the percentage of participants who met that threshold for either buttock or either thigh. Thus, it records whether an improvement threshold was reached, not how large the improvement was on average. It also does not establish that improvement occurred in every treated area or on both sides.

A responder percentage is a direct way to describe how often a prespecified categorical outcome occurred in each group. It is readily interpretable as a proportion of participants meeting a defined rating threshold. The endpoint is investigator-rated, however, and the scale relies on judgment about appearance relative to pretreatment. Because masking was listed as none, the potential influence of awareness of treatment assignment on ratings is relevant when interpreting the result. The registry does not report a patient-rated primary endpoint or a blinded assessment.

The primary endpoint includes a 95% confidence interval for each reported percentage. A confidence interval communicates uncertainty around an estimated response proportion; the interval is especially important when the group estimates are based on a small number of participants. It does not by itself establish that techniques differ. The registry record does not report an inferential comparison between the groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a binary percentage: each participant is classified as meeting or not meeting the responder definition, and the reported group result is the percentage classified as responders. In this trial, the responder definition is an I-GAIS rating of +1 or better for either buttock or either thigh at Day 180. A percentage preserves the clinical meaning of the threshold, but it does not show the distribution of scores among responders or distinguish a rating of +1 from a rating of +3.

The registry reports a 95% confidence interval alongside each percentage. General statistical explanation: a confidence interval reflects the imprecision of an estimate under a specified statistical procedure. It gives a range of values compatible with the observed data and the method’s assumptions. It is not a guarantee that the true response percentage lies in the interval, and it is not a direct probability that one technique is better. The exact procedure used to calculate these intervals is not reported in the registry record.

What do the group estimates say?

Each percentage describes its own technique-and-site group. The buttock estimates are 85.7% and 87.5%, and the thigh estimates are 75.0% and 80.0%, with the corresponding 95% confidence intervals reported separately. These numbers are descriptive. A comparison between techniques requires a contrast that directly estimates the difference between groups, rather than relying on separate percentages or visual comparison of their intervals. No such comparison is reported for the primary endpoint.

General statistical explanation: estimates based on small groups tend to be less precise than estimates based on larger groups, all else being equal. The interval width is one way to see that uncertainty. A broad interval leaves room for a range of underlying response percentages, so a point estimate should not be treated as an exact or stable value. The intervals in this study are broad, and the listed endpoint group counts are 7, 8, 8, and 10 participants.

Why does the analysis population matter?

The mITT population includes enrolled participants who received at least 1 CCH injection and had at least 1 valid I-GAIS evaluation after injection. The resulting endpoint percentages therefore refer to people meeting those criteria, not automatically to everyone enrolled. General statistical explanation: defining an analysis population helps clarify which participants contribute to a result. Excluding participants without a qualifying outcome can affect an estimate if the reasons for missingness are related to treatment or outcome. The registry does not report the number of participants excluded from this endpoint, reasons for missing evaluations, or how missing endpoint values were handled.

The registry’s sample-size assumptions describe planning illustrations based on an observed effect, not the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. General statistical explanation: a planning illustration estimates the group size that a future study might need under its assumptions. Such a calculation is not a measure of the probability that the completed study detected an effect. The registry record does not report the study’s own sample-size justification, and planning illustrations must not be interpreted as observed power.

What does the missing comparison mean?

The record does not give a two-arm comparison for the binary primary endpoint. General statistical explanation: a comparative analysis would ordinarily state the contrast of interest, such as a difference in responder percentages, and quantify uncertainty for that contrast. An analysis may also adjust for design features, but the adjustment method depends on the prespecified plan and data structure. No comparative estimate, confidence interval for a contrast, p-value, or adjustment method is reported in the registry record. A comparison cannot be reconstructed responsibly from the group percentages alone without choosing assumptions and a method that are not documented.

The registry lists several secondary outcomes: I-GAIS and Subject Global Aesthetic Improvement Scale responder percentages, change in Body-Q Appraisal of Cellulite Total Score, change in the Hexsel Cellulite Severity Scale subsection D severity score, and antibody outcomes for anti-AUX-I, anti-AUX-II, and neutralizing antibodies. Those outcomes can address different aspects of appearance, participant assessment, severity, or immune response. Their results and detailed analysis methods are not reported in the registry record.

Why do multiple outcomes matter?

General statistical explanation: when many outcomes or comparisons are examined, the chance of observing an apparently notable result by chance can increase if each is assessed separately. Multiplicity methods can control or describe this issue, but the choice depends on which outcomes and comparisons were planned. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or whether any interim analyses were conducted. It is therefore not possible to determine how the reported endpoint was situated within a broader testing plan.

Randomization supports a fair comparison in expectation when assignment is implemented as intended, but it does not remove uncertainty in a small study. Open-label assessment also matters because the primary measure is an investigator judgment. General statistical explanation: masking can reduce the risk that knowledge of assignment influences ratings or measurement. The registry lists masking as none and does not report other protections against assessment bias. Taken together, the endpoint estimates are useful as descriptive observations, while a precise comparative conclusion requires analysis details and comparative results that are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Uniform 0.1-mL 1-Aliquot Grid Injection Technique ", "Uniform 0.3-mL 2-Aliquot Grid Injection Technique ", "Uniform 0.1-mL 1-Aliquot Grid Injection Technique ", "Uniform 0.3-mL 2-Aliquot Grid Injection Technique ")
n      <- c(7, 8, 8, 10)
events <- c(6, 7, 6, 8)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Uniform 0.1-mL 1-Aliquot Grid Injection Technique   7  6  85.7  42.1  99.6  48.7  97.4  47.3  96.8
ARM  Uniform 0.3-mL 2-Aliquot Grid Injection Technique   8  7  87.5  47.3  99.7  52.9  97.8  51.8  97.2
ARM  Uniform 0.1-mL 1-Aliquot Grid Injection Technique   8  6  75.0  34.9  96.8  40.9  92.9  40.0  92.5
ARM  Uniform 0.3-mL 2-Aliquot Grid Injection Technique   10  8  80.0  44.4  97.5  49.0  94.3  48.2  94.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and six secondary outcomes. The secondary outcomes cover investigator-rated and subject-rated improvement, changes in Body-Q and Hexsel scores, and antibody findings. Examining multiple outcomes creates a multiplicity question: general statistical explanation, if many hypotheses are tested independently, the likelihood of at least one apparently positive finding by chance can rise. Analysts may address this through a prespecified hierarchy or adjustment, but the appropriate approach depends on the study’s analysis plan. A multiplicity strategy is not reported in the registry record.

The record does not report whether interim analyses were planned or conducted, whether the secondary outcomes were exploratory or confirmatory, or which comparisons were prespecified. Results for the secondary outcomes are not reported in the registry record. The primary endpoint is reported by group, but a two-arm comparison is not available, and no inferential test is presented. Without these details, the results cannot be placed within a complete testing framework.

The primary analysis population is the mITT population, defined as enrolled participants who received at least 1 CCH injection and had at least 1 valid I-GAIS evaluation after injection. The registry does not report the number or characteristics of participants without a valid evaluation, reasons for missing data, or the method used to handle missing outcomes. It also does not describe whether any sensitivity analyses were used to assess the effect of missingness. General statistical explanation: missing-data handling can matter when the probability of having an observed outcome is related to treatment assignment or the outcome itself.

The registry does not report a per-protocol population or other analysis populations. It does not provide a sample-size justification for the trial. The sample-size assumptions are planning illustrations based on the observed effect and should not be read as evidence of observed power. These reporting gaps limit assessment of how fully the endpoint analyses followed a prespecified statistical plan.

12. 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 non-serious adverse event terms

The registry reports serious adverse events and other adverse events separately for the two technique groups, combining buttock or thigh treatment areas within each group. For the 0.1-mL 1-aliquot technique, 16 participants were listed as at risk for serious adverse events and 0 were affected; 16 were listed as at risk for other adverse events and 16 were affected. For the 0.3-mL 2-aliquot technique, 19 participants were listed as at risk for serious adverse events and 0 were affected; 19 were listed as at risk for other adverse events and 19 were affected. No deaths were reported in either group.

These are counts of participants, not a detailed description of event types, severity, timing, or duration. The record lists no top serious adverse-event terms, and further details about the other adverse events are not reported in the registry record. The reported counts therefore show that no serious adverse events or deaths were recorded in these groups, while other adverse events were recorded for all participants listed as at risk in each group. They do not identify which events occurred or whether events were judged related to CCH.

General statistical explanation: the absence of observed serious events in a small study does not establish that the risk is absent. Safety counts should be interpreted alongside the size and duration of observation, event definitions, and completeness of reporting. The registry gives no additional event-level information or longer-term safety results here, so these figures should be read as a limited description of the recorded events rather than a complete characterization of safety.

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

The primary results describe the proportion of participants meeting a defined investigator-rated improvement threshold at Day 180 in each listed technique-and-site group. The percentages range from 75.0% to 87.5%, and each is accompanied by a broad 95% confidence interval. These figures are observations in the study’s mITT population, not precise predictions of what would occur in another population or setting.

The results do not establish that one injection technique is superior to the other. The registry does not report an inferential comparison between techniques, and the group-specific percentages are not a substitute for a direct contrast with uncertainty. Nor do the results establish equivalence: absence of a reported difference is not evidence that the techniques perform alike. The registry record does not report a noninferiority or equivalence analysis.

The results also do not isolate the effect of CCH compared with no treatment, because no untreated or placebo group is listed. They do not separate treatment effects from other influences on appearance ratings over time. The open-label design and investigator-rated endpoint leave the possibility that expectations or knowledge of treatment could affect assessments; the registry does not describe masking or other assessment safeguards.

The responder definition captures a rating of Improved (+1) or better for either buttock or either thigh. It does not mean that every treated area improved, and it does not convey the magnitude of improvement among responders. It is distinct from a change in a severity score or a participant’s own global assessment. Those are included among the listed secondary outcomes, but their results are not reported in the registry record.

The adverse-event counts report no serious events and no deaths in the listed groups, while other adverse events were recorded for all participants listed as at risk. This is a description of the registry counts, not proof that serious harm cannot occur. Event types and further safety details are not reported in the registry record. Overall, the posted results offer descriptive group estimates and limited safety counts. Their interpretation is constrained by the small endpoint groups, uncertainty around the estimates, open-label assessment, and lack of comparative statistical results.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between describing response within groups and comparing treatments. A percentage with a confidence interval describes an estimate for one group. The question of whether two injection techniques differ requires an estimate of the contrast between them and uncertainty around that contrast. The registry reports the former for the primary endpoint but not the latter. This distinction prevents a reader from treating numerical separation between point estimates as a demonstrated treatment difference.

The design also separates technique from treatment area in its listed groups. Buttock and thigh outcomes are reported independently, which is relevant because the study question concerns two techniques across both locations. A comparison across different locations would combine differences in technique with differences in treatment area. Within-location contrasts would speak more directly to technique, but no formal comparison is reported. Clear identification of the estimand—the exact contrast the study intends to estimate—is important for interpreting a multi-arm clinical study.

Precision is another central issue. The endpoint groups contain 7, 8, 8, and 10 participants, and the confidence intervals are broad. General statistical explanation: small group estimates can be sensitive to individual observations, and broad intervals communicate that the observed percentages are not known with high precision. This is why the confidence interval deserves attention alongside the point estimate.

The endpoint’s binary responder threshold makes the outcome easy to interpret, but compresses a 7-point scale into responder and non-responder categories. It does not retain all distinctions in the original ratings. The open-label design adds a separate concern because the outcome is investigator-rated. Finally, the registry lists multiple secondary outcomes without reporting their results or a multiplicity strategy. Together, these features make the record a case study in reading descriptive endpoint estimates carefully and distinguishing them from confirmatory evidence about comparative effects.

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 trial-specific limitations constrain interpretation. The registry reports a small number of participants in each primary endpoint group: 7, 8, 8, and 10. The confidence intervals around the responder percentages are correspondingly broad, so the point estimates should not be treated as highly precise. The registry does not provide a two-arm comparison for the primary endpoint, which prevents a direct assessment of the technique contrasts from the posted results.

The study was open label, with masking listed as none, and the primary endpoint depends on an investigator’s global rating. The registry record does not describe blinded assessment, standardized photographic review, or other procedures intended to reduce assessment bias. The endpoint also combines a response in either buttock or either thigh; it does not show whether a response occurred in all treated areas or how scores varied among responders.

The listed arms pair technique with treatment area. Although both techniques are represented for buttocks and thighs, the registry does not report formal within-site contrasts. Comparisons that cross sites would not isolate technique alone. The record does not report the allocation ratio, randomization procedure, or details of treatment visit timing and number. The arm descriptions state the maximum dose per visit and amount per treatment area, but do not establish the actual dosing received by each participant over the study.

Important analysis details are also absent. The registry does not report how missing outcome data were handled, the method used to calculate confidence intervals, the sample-size justification, or the multiplicity plan. Secondary outcome results are not reported in the registry record. Safety information is limited to participant counts; event types, severity, relatedness, and timing are not reported. These limitations do not invalidate the posted descriptive results, but they restrict what can be concluded from them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CCH Treatment of Cellulite in the Presence of Dermal Laxity With Comparison Between Two (2) Different Injection Techniques — NCT04580303.
• Registry record last updated 2022-09-28; status last verified 2022-08.
• Results first posted 2022-09-28.
• 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

NCT04580303 is a completed phase 2, multicenter, open-label, randomized, parallel-group, multiple-dose study of CCH injection techniques for cellulite with dermal laxity in adult females. The registry lists enrollment of 35 and a study start date of 2020-10-01, with primary completion on 2021-08-30. The primary endpoint was the percentage of mITT participants with an I-GAIS score of +1 or better for either buttock or either thigh at Day 180.

Group-specific responder percentages ranged from 75.0% to 87.5%, with broad 95% confidence intervals. No two-arm comparative result for the primary endpoint is reported in the registry record. The record lists no serious adverse events or deaths, and reports other adverse events for all participants listed as at risk in each technique group, without event-level details. Missing-data methods, multiplicity procedures, secondary results, and the trial’s sample-size justification are not reported in the registry record.