Saypha® Volume LIdocaine in Nasolabial Folds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Saypha® Volume LIdocaine in Nasolabial Folds (NCT04883632), a randomized na study. The primary outcome is Responder Rate in Reduction of Nasolabial Folds.

2. Clinical Question

The record describes a prospective, randomized, multicenter study and names moderate to severe nasolabial folds as the condition. Its primary outcome is a responder count, with the responder definition based on change from baseline. The result therefore concerns the frequency of meeting that specified improvement threshold at the stated assessment time. It is not a comparison of average scale changes, and the posted outcome does not by itself describe the amount of improvement among participants who met the threshold.

3. Trial Design

The study is titled as an evaluation of Saypha Volume Lidocaine for correction of nasolabial folds. It is recorded as randomized, triple-masked, and parallel-group, with an enrollment of 110. Its official title describes a prospective, randomized, multicenter study. The registry lists the study status as completed, a start date of 2019-11-05, and a primary completion date of 2021-05-27. The phase is recorded as NA.

The two intervention arms received Saypha Volume Lidocaine manufactured at different Croma-Pharma locations: the HQ Facility and the C1 Facility. The registry describes the overall population as both manufacturing-location groups combined. This is therefore a comparison of the same named product from two manufacturing locations. Additional details about allocation procedures, masking implementation, treatment administration, eligibility criteria beyond the stated condition, or the sites involved are not reported in the registry record.

The primary outcome is the responder rate in reduction of nasolabial folds at 24 Weeks. The posted arm results include 34.0 responders among 53.0 participants for HQ and 39.0 among 53.0 for C1; the overall-population entry reports 73.0 among 106.0. The registry's enrollment figure is 110, while the numbers in the posted primary outcome are different. Reasons for the difference, and the disposition of participants between enrollment and the outcome analysis, are not reported in the registry record. Safety figures use their own at-risk counts and are described separately.

The registry lists two secondary outcomes: proportion of responders at other time points and change versus baseline in nasolabial-fold severity. It records 13 outcome measures and 0 analyses. The registry record does not report the original sample-size justification or the trial's own statistical analysis plan.

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: The primary data set for analyses of performance of the investigational device and of aesthetic effects will contain all data collected in the Intent-to-treat population, which is defined as all subjects who received the investigational device and have at least one post-treatment assessment, but for this analysis we have to consider the number of subjects with trial completion at Week 24, threfore an overal population of 106.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The data sets contain all data collected in the Intent-to-treat population (ITT), which is defined as all subjects who received the investigational device and have at least one post-treatment assessment N =109 The SAF (Safety analysis Set) also has N = 109 Number of subjects with trial completion at week 24: N =106

6. Primary Endpoint

The registry lists the primary outcome as Responder Rate in Reduction of Nasolabial Folds, measured over 24 Weeks.

The primary endpoint is the number and proportion of participants classified as responders at 24 Weeks. A responder is defined as having at least a one-grade improvement from baseline on the Nasolabial Folds Severity Rating Scale on both sides of the face. The scale is a validated five-grade measure: 0 is none or minimal, 1 is mild, 2 is moderate, 3 is severe, and 4 is extreme. A lower grade corresponds to less severe folds.

A responder endpoint converts a graded assessment into a yes-or-no outcome using a prespecified threshold. It answers how often participants meet that threshold, rather than showing the full distribution of scale changes or the average change. That distinction matters because participants with different amounts of improvement can all qualify as responders once they cross the threshold. Conversely, a change that does not meet the threshold does not count as a response under this definition.

This endpoint is used to describe the proportion reaching the stated improvement criterion and to compare that proportion between manufacturing-location groups. The posted outcome includes counts and denominators for each group and an overall-population entry. It does not give participant-level scale scores or explain how assessments were handled if a score was unavailable.

7. Results Posted in the Registry

• Volume Lidocaine C1: 73.6% (39/53) versus 64.2% (34/53) on control; risk difference 9.4 percentage points (95% CI -8.1 to 27.0), risk ratio 1.15 (0.89–1.48); unadjusted two-proportion z-test p = 0.294.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: each participant either meets the responder definition or does not. For a binary endpoint, a proportion expresses the number meeting the definition relative to the number assessed in that group. The posted values are 34.0 of 53.0 in HQ and 39.0 of 53.0 in C1, with an overall entry of 73.0 of 106.0. The comparison lists proportions of 0.641 and 0.736. These describe the outcome frequencies in the posted analysis data; they do not show the full scale-score changes behind the classifications.

What does the risk difference represent?

The risk difference is the C1 responder proportion minus the HQ responder proportion. Its estimate is 0.094. An absolute difference is useful because it expresses the contrast on the same proportion scale as the endpoint. A positive value means the estimated responder proportion is higher in C1 than in HQ; a negative value would mean it is lower. The sign describes the direction of the estimate, not whether the result is conclusive.

How should the confidence interval be read?

A confidence interval conveys uncertainty around an estimated effect. Rather than treating the observed estimate as exact, it gives a range of values compatible with the data and the calculation method. For the risk difference, the interval is -0.081 to 0.270. Because that range contains zero, it includes the possibility of no difference, while also extending to estimates favoring either group. The interval is broad enough that the data do not pin down a narrow range of plausible differences. The confidence level and the detailed interval method are not reported in the registry record.

What does the p-value add?

The unadjusted p-value is 0.294. A p-value describes how unusual the observed data, or data more extreme, would be under a specified no-difference model and its assumptions. It is not the probability that the no-difference model is true, and it does not measure the size or importance of an effect. The registry record does not report an adjusted p-value or a multiplicity procedure. The listed p-value should therefore be read as unadjusted, not as evidence that accounts for all outcomes or time points.

Why does the endpoint definition matter?

The responder classification depends on a threshold: at least a one-grade improvement from baseline on both sides of the face. The underlying Nasolabial Folds Severity Rating Scale has grades from 0 to 4, with lower grades indicating less severe folds. Converting that graded information into a binary outcome makes the result straightforward to express as a proportion, but it loses detail. It does not distinguish a participant who just meets the threshold from one with a larger improvement, and it places all participants who do not meet the threshold in the same category.

What can be inferred from the posted comparison?

The estimated difference is based on the posted group counts and proportions. The registry does not report an adjusted model, covariate adjustment, or a detailed analysis procedure for this endpoint. The comparison should therefore be read as an unadjusted group contrast, not as an estimate adjusted for baseline factors. The record also lists 0 analyses even though it posts outcome counts and a comparison. Additional detail about the statistical model or the sponsor's analysis is not reported in the registry record.

In general, randomization is intended to support a fair comparison of groups by allocating participants without selecting the group according to known characteristics. Masking is intended to limit the influence of knowledge of assignment on relevant study processes. Those are general purposes of these design features, not confirmation of how allocation or masking was implemented in this study. The registry identifies the design as randomized and triple-masked but does not describe the practical procedures.

Finally, the endpoint result depends on which participants had an available assessment and how missing observations were handled. The record provides a partial description of the primary data set, but the full definition and missing-data methods are not reported in the registry record. These details matter because the analyzed outcome population may differ from all enrolled participants, and because assumptions about unavailable assessments can affect a responder proportion.

10. Confidence Intervals and Precision

The risk-difference estimate is 0.094, with a confidence interval from -0.081 to 0.270. The interval is important alongside the point estimate: the point estimate is the single value calculated from the observed group results, while the interval communicates uncertainty around that value. Its lower end is below zero and its upper end is above zero, so the data are compatible with a range that includes no group difference and effects in either direction.

The interval is not especially narrow relative to the estimated difference. It therefore leaves substantial uncertainty about the size and direction of the underlying contrast. The unadjusted p-value of 0.294 is consistent with the interval's inclusion of zero, but the p-value and interval serve different descriptive roles: the p-value summarizes compatibility with a no-difference model, while the interval displays a range of plausible effect estimates. Neither determines whether an effect would matter in practice.

The confidence level and method used to construct the interval are not reported in the registry record. The posted arm counts and the registry enrollment number also differ, and the reasons are not reported. No additional arm-level confidence intervals are included in the registry record for the responder proportions. As a result, the interpretation of precision is limited to the posted interval for the risk difference and the observed counts. The result should not be treated as a precise estimate of the true contrast, nor should the interval be read as proof that the groups are the same.

11. 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 figures describe participants per arm, not total participants across the trial and not total events. They are illustrations based on the observed effect rather than the trial's own original design assumptions. The calculation assumptions listed in the registry record are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect.

For planning for 100% of the observed effect, the figures are 377 participants per arm for 80% power and 505 participants per arm for 90% power. For planning for 75% of the observed effect, they are 685 participants per arm for 80% power and 917 participants per arm for 90% power. For planning for 50% of the observed effect, they are 1,571 participants per arm for 80% power and 2,102 participants per arm for 90% power.

The 80% power column gives the illustrated number of participants per arm for a study with an 80% chance of detecting the specified effect under the listed assumptions, if the assumed effect and analysis conditions apply. The 90% power column makes the analogous illustration for a 90% chance. These are design-planning quantities, not outcomes from the completed study. This is not observed power.

Smaller effects are harder to distinguish from random variation, so the planning illustration requires more participants per arm as the assumed effect becomes smaller. The figures depend on the stated assumptions and the observed effect used as their starting point. The registry record does not report the trial's original sample-size justification or confirm that its initial design used these assumptions.

12. 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 = 0.642; treatment proportion p₁ = 0.736; average p̄ = 0.689.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6548 = 1.2834.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6514 = 0.5483.
4. n = (1.2834 + 0.5483)² / (0.0943)² = 377.0, rounded up to 377 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 <- 0.641509433962264                          # control proportion
p1 <- 0.735849056603774                          # 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(4883632)
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 = 377 (80% power), 505 (90% power)
 75% of observed effect: n per arm = 685 (80% power), 917 (90% power)
 50% of observed effect: n per arm = 1,571 (80% power), 2,102 (90% power)
power.prop.test: 377 
Simulated power at n = 377 per arm: 0.805 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and two secondary outcomes: proportion of responders at other time points and change versus baseline in nasolabial-fold severity. It also records 13 outcome measures and 0 analyses. The primary endpoint is assessed at 24 Weeks and is described as analyzed separately for C1 and HQ as well as for the overall population. Considering several outcomes, time points, or population summaries can create multiple opportunities to observe a result that appears notable by chance.

The registry record does not report whether the trial used a multiplicity adjustment, a hierarchy for testing outcomes, or another method to control the interpretation of multiple comparisons. The p-value listed for the C1-versus-HQ comparison is unadjusted. It should not be assumed to account for other outcomes or time points. Nor does the absence of a reported adjustment establish that no adjustment was used; the procedure is not reported in the registry record.

The primary population description says the analysis data set contains all data collected in the intent-to-treat population, defined as participants who received the investigational device and had at least one post-treatment assessment. The remainder of that definition is incomplete in the registry record. The record does not report a complete analysis-population definition, the handling of participants without a post-treatment assessment, or the treatment of missing outcome data. It also does not describe imputation, sensitivity analyses, or reasons for missingness.

The posted primary outcome counts use 53.0 participants in each manufacturing-location group and 106.0 in the overall entry, while enrollment is listed as 110. The registry record does not explain the difference. Safety figures use separate at-risk counts. Without disposition details, it is not possible to determine from the registry record why the denominators differ or whether missingness could affect the responder comparison.

14. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (1.9%), intervertebral disc protrusion (1.8%), vertebral foraminal stenosis, (1.8%).

For serious adverse events, the HQ group lists 1 affected participant among 54 at risk, and the C1 group lists 2 among 55 at risk. The overall-population entry lists 3 among 109 at risk. The registry lists 0 deaths for each of these entries. These counts should be read with their corresponding at-risk denominators; they are not the same denominators as those in the primary outcome.

The record also lists serious-event terms with percentages: appendicitis at 1.9%, intervertebral disc protrusion at 1.8%, and vertebral foraminal stenosis, at 1.8%. The registry record does not give further context for interpreting these listed term percentages, including their group assignment in the registry record. They should not be used to infer a comparative risk between manufacturing-location groups.

The separate counts for other adverse events are 16 among 54 at risk for HQ, 14 among 55 at risk for C1, and 30 among 109 at risk overall. These are not serious-event counts. The registry record does not provide event-level detail or a full accounting of timing, severity, or relatedness in the registry record. The safety figures are descriptive counts and do not establish that an event was caused by the intervention or that the groups differ in safety.

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

The primary result describes how often participants met a specific responder definition at 24 Weeks. The observed responder proportion was 0.641 for HQ and 0.736 for C1, with an estimated risk difference of 0.094 for C1 relative to HQ. The confidence interval from -0.081 to 0.270 shows that the estimate is uncertain and includes zero. The unadjusted p-value is 0.294. The posted data therefore give a numerical contrast, but they do not establish a clear difference between the manufacturing-location groups.

This result is about a thresholded scale outcome. It does not tell how much the score changed for each participant, whether improvement below the responder threshold occurred, or how the full distribution of severity scores differed. The overall-population result combines the two manufacturing-location groups; it is not a separate comparison against no treatment, another product, or an untreated group.

The finding should also be distinguished from a claim about the product's effect in a broader population. The registry record describes a randomized comparison of Saypha Volume Lidocaine made at two facilities, with no other comparator arm listed for this endpoint. It does not report a treatment-versus-no-treatment contrast. The result cannot by itself answer what would have happened to participants without the product or with a different intervention.

Finally, interpretation is bounded by the reported outcome population, missing-data information, and uncertainty. The trial's enrollment is 110, while the primary outcome entry uses 106.0 participants overall; the reason is not reported in the registry record. The complete analysis-population definition, missing-data handling, and detailed analysis plan are also not reported. The results describe the posted information, rather than providing medical advice or a conclusion about an individual's expected outcome.

16. Why This Trial Matters Statistically

This study raises a useful statistical distinction between comparing products and comparing manufacturing locations. The two randomized groups received the same named intervention, Saypha Volume Lidocaine, while the registry distinguishes the HQ and C1 manufacturing facilities. The primary contrast is therefore specifically about responder proportions across those groups, not a general treatment-effect comparison against a different intervention.

The endpoint also illustrates how a clinical scale can be converted into a binary outcome. Requiring at least a one-grade improvement on both sides creates a clear responder definition, but it necessarily discards detail about the magnitude of change. Readers need to keep that threshold in mind when interpreting the count and proportion of responders.

The posted comparison is a useful example of why an estimated effect should be considered together with its uncertainty. The C1 estimate is higher, but the interval from -0.081 to 0.270 includes zero and spans effects in either direction. The p-value of 0.294 does not settle whether a difference exists or whether a possible difference would be important. The data support a cautious description of the estimate rather than a definitive conclusion about the groups.

Finally, the registry record leaves important analysis details unreported, including the full analysis-population definition, missing-data handling, multiplicity procedures, and the trial's original sample-size rationale. Recognizing these gaps is part of sound statistical interpretation: results can be described precisely while the limits of what can be inferred remain clear.

17. 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 details needed to assess the result are not reported in the registry record. The enrollment is listed as 110, whereas the primary endpoint reports 53.0 participants in each manufacturing-location group and 106.0 in the overall population. The reason for the difference, participant flow, and any exclusions from the primary analysis are not reported.

The primary data set is described only in part: participants had to receive the investigational device and have at least one post-treatment assessment, but the remainder of the definition is incomplete. The registry record does not report how missing Week 24 assessments were handled, whether any outcome values were imputed, or whether sensitivity analyses were performed. This limits assessment of how the analyzed participants relate to all enrolled participants.

The record does not report the trial's original sample-size justification, its detailed statistical analysis plan, or any multiplicity procedure. Although planning illustrations based on the observed effect are listed, they are not the study's original design assumptions. The confidence-interval method and confidence level are also not reported. The analysis count is listed as 0, despite posted outcome counts and a comparison, and no further analysis detail is available in the registry record.

The primary endpoint is a responder threshold assessed at 24 Weeks. The posted primary result does not give the distribution of scale-score changes, and results for the listed secondary outcomes are not included in the registry record. Follow-up beyond the primary timeframe is not reported in the registry record. These omissions constrain interpretation of outcome detail and duration, without changing what the posted primary counts themselves state.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Saypha® Volume LIdocaine in Nasolabial Folds — NCT04883632.
• Registry record last updated 2025-04-03; status last verified 2024-12.
• Results first posted 2025-04-03.
• 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.

21. Record Summary

The registry record describes a completed, prospective, randomized, triple-masked, parallel-group, multicenter study of Saypha Volume Lidocaine for moderate to severe nasolabial folds. The groups received product manufactured at the Croma Pharma HQ Facility or C1 Facility. Enrollment is listed as 110, and the primary assessment is at 24 Weeks.

The primary endpoint is a responder definition based on at least a one-grade improvement on both sides of the face. The posted comparison reports proportions of 0.641 for HQ and 0.736 for C1, with an estimated risk difference of 0.094, a confidence interval from -0.081 to 0.270, and an unadjusted p-value of 0.294. The estimate is uncertain and the interval includes zero.

The registry lists two secondary outcomes, 13 outcome measures, and 0 analyses. Important details about the full analysis population, missing data, multiplicity, and original sample-size rationale are not reported in the registry record.