AkLief Evaluation in Acne-induced Post-Inflammatory Hyperpigmentation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AkLief Evaluation in Acne-induced Post-Inflammatory Hyperpigmentation (NCT05089708), a randomized phase 4 study. The primary outcome is Absolute Change From Baseline in Post-Inflammatory Hyperpigmentation (PIH) Overall Disease Severity (ODS) Scores at Week 24.

2. Clinical Question

The clinical question is about the comparative change in this score under the two assigned creams. It does not, by itself, establish whether either arm changed relative to no treatment, because the registry record reports changes in both randomized arms and a between-arm comparison. The randomized comparison is the central basis for interpreting whether the observed Week 24 score changes differed between the assigned groups.

3. Trial Design

This was a randomized, double-masked, parallel-group Phase 4 study with an enrollment of 123 participants. The registry record lists acne vulgaris as the condition and describes the study as evaluating trifarotene 50 mcg/g cream against its vehicle cream in participants with moderate facial acne and risk of acne-induced PIH. The treatment period relevant to the study question was 24 weeks.

The two arms were trifarotene (CD5789) cream and trifarotene vehicle cream. The registry reports 60 participants in the trifarotene arm and 63 in the vehicle arm for the primary outcome. The primary population was the Intent to Treat population, defined in the record as all randomized participants. The registry lists Galderma R&D as sponsor and records the study as completed.

Random assignment supports a between-arm comparison by reducing the role of deliberate treatment selection, while masking is intended to limit knowledge of assigned treatment from influencing trial conduct or outcome assessment. These are general design principles; the registry record does not describe the specific randomization procedure or masking procedures. It also does not report the planned allocation ratio or details about treatment adherence.

The study began on 2021-12-22, and primary completion was recorded as 2022-12-15. Those dates describe the record’s study timeline; they do not establish when each participant entered or completed treatment. The registry does not report the detailed schedule of visits beyond the outcome timeframes listed, nor does it describe site locations or participant-level follow-up.

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: A total of 150 participants were screened, out of which 123 participants were randomized and enrolled in two treatment groups. 60 participants were randomized in Trifarotene (CD5789) Cream treatment group and 63 were assigned in Trifarotene Vehicle Cream treatment group.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Intent to Treat (ITT) population included all participants who were randomized.

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 Absolute Change From Baseline in Post-Inflammatory Hyperpigmentation (PIH) Overall Disease Severity (ODS) Scores at Week 24, measured over Baseline and Week 24.

The primary endpoint was absolute change from baseline in the PIH Overall Disease Severity score at Week 24, expressed as a score on a scale. The PIH ODS instrument is described as a 9-point scale, ranging from Grade 0, Normal, through Grade 8, Severe (very distinctive). Intermediate grades describe increasing degrees of visible PIH, including mild, moderate, marked, and severe categories.

The endpoint measures the clinician-rated severity level at follow-up relative to baseline. Its change score captures whether the recorded severity moved upward or downward during the study period. The registry specifies that a negative change indicates a reduction in PIH disease severity score from baseline. Because the outcome is a score, it represents an ordered clinical assessment rather than a direct count of lesions or a laboratory measurement.

Using a baseline-to-follow-up change is a way to describe how the measured condition varies over the treatment period while accounting for each participant’s starting score in the outcome definition. Comparing the arm-level changes addresses the study’s central comparative question. The registry reports least-squares means and standard errors for the arms. It does not describe the model or adjustment factors used to obtain those least-squares means, so further claims about that analysis cannot be made from the record.

The endpoint is useful for studying PIH because the study specifically concerns acne-associated hyperpigmentation. It should be interpreted as evidence about the recorded ODS score at the specified follow-up, not as a complete measure of every aspect of PIH or of acne.

7. Results Posted in the Registry

• Trifarotene (CD5789) Cream: mean -2.10 versus -2.10 on control; difference 0.00 (95% CI -0.71 to 0.71), standardized effect d = 0.00; z-test p = 1.000.

8. Secondary Efficacy Endpoints

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

Percent Change From Baseline in PIH ODS Scores at Week 24

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Trifarotene (CD5789) Cream: mean -45.40 versus -44.90 on control; difference -0.50 (95% CI -15.64 to 14.64), standardized effect d = -0.01; z-test p = 0.948.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Trifarotene (CD5789) Cream and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the assessment beyond the primary absolute change in PIH ODS score at Week 24. They include percent change at Week 24 and absolute or percent change at earlier listed visits. The secondary result with numerical arm summaries in the registry is the Week 24 percent change outcome. Its general direction is consistent with the primary result: the posted arm summaries are similar rather than showing a marked separation. No further endpoint-by-endpoint numerical interpretation is repeated.

The registry record lists additional secondary outcomes for absolute change at Weeks 12, 16 and 20, and percent change at Weeks 12, 16 and 20. Numerical results for those listed outcomes are not reported in the registry record. Their inclusion in the outcome list should not be taken as evidence about their direction or magnitude. The available secondary results therefore do not provide a complete account of how the endpoint pattern evolved across the planned follow-up times.

Secondary outcomes can help describe whether a result is consistent across related measures or timepoints, but their interpretation depends on how many comparisons were considered and how the analysis handled that multiplicity. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for these secondary comparisons. Any unadjusted secondary significance result, if one were available, would consequently merit less weight than a result interpreted under a prespecified strategy that accounts for multiple testing. The posted registry results list no reported analyses for the outcomes.

In relation to the primary result, the available Week 24 secondary summary does not materially change the broad picture of similar arm-level findings. It should be viewed as supporting context, not as independent confirmation: the secondary measure concerns the same underlying PIH score and follow-up period. The absent numerical results at other listed timepoints limit claims about consistency over time.

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

• Percent Change From Baseline in PIH ODS Scores at Week 24
• Absolute Change From Baseline in PIH ODS Scores at Weeks 12, 16 and 20
• Percent Change From Baseline in PIH Overall Disease Severity Scores at Weeks 12, 16 and 20

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a score, and the reported arm summaries are least-squares means with standard errors. General statistical explanation: a mean summarizes the central value of a continuous outcome, while a standard error describes the estimated precision of that mean. A standard error is not the spread of individual participant scores; it reflects uncertainty in an estimated mean.

What does the between-arm estimate represent?

The comparison is the trifarotene arm’s mean change minus the vehicle arm’s mean change. A value of 0.0 means that the displayed arm means do not differ at the reported precision. A positive value would mean a greater numerical change in the trifarotene arm under this subtraction order, while a negative value would mean a smaller numerical change. Because the endpoint’s negative values indicate reduced severity from baseline, the sign of a contrast must be interpreted together with the scale definition, not in isolation.

The arm-level least-squares means are reported as -2.1 for both groups. Least-squares means are model-based adjusted means in general statistical usage. However, the model and any adjustment variables are not reported in the registry record. It is therefore not possible to explain which factors, if any, were included in the sponsor’s calculation or how the posted means were estimated.

What is the status of the recalculated comparison?

The unadjusted comparison is recalculated from posted summary statistics. It is not a sponsor-reported analysis. The calculation uses the arm means and standard errors, with an approximate pooled standard deviation noted in the registry-derived analysis. Such a recalculation is a compact way to describe the posted summaries, but it cannot reproduce an analysis whose model, covariate adjustments, missing-data handling, or other details are not reported. The registry record lists no reported analyses for the outcomes.

The recalculated primary contrast is 0.0, with a 95% confidence interval from -0.708 to 0.708 and an unadjusted p-value of 1.0. General statistical explanation: a p-value summarizes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. Here, the unadjusted p-value should not be treated as a reported sponsor result or as a substitute for the interval and design context.

Why does over-dispersion matter?

General statistical explanation: over-dispersion occurs when the observed variability is greater than a statistical model expects. If a model underestimates variability, standard errors can be too small and confidence intervals too narrow; if it accounts for variability appropriately, uncertainty estimates are more credible. The primary endpoint is a bounded, ordered score, but the registry record does not describe a distributional model or report an over-dispersion assessment. No claim about over-dispersion in this trial is warranted. The recalculation’s approximate standard deviation is a summary-statistic device and should not be confused with evidence that a particular model fits the outcome.

How should the planning illustrations be read?

The sample-size illustrations are based on the observed effect and are planning scenarios, not observed power. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and detection of a stated fraction of the observed effect. The planning counts are expressed as participants per arm. They illustrate how a target effect and assumptions can inform a future design; they do not establish the probability that this completed trial detected an effect, and they are not the trial’s enrollment justification. The protocol’s sample-size rationale is not reported in the registry record.

General statistical explanation: planning based on an observed effect can be unstable, particularly when the observed estimate is close to zero. A small estimated effect can imply very large sample-size requirements under the same assumptions, while a larger estimated effect can imply smaller requirements. Such illustrations should be treated cautiously because an observed effect is itself uncertain and may not be the effect a future study aims to detect. No additional calculation is needed to interpret the planning figures posted for this trial.

What does the endpoint scale imply?

The PIH ODS score has ordered grades from 0 to 8. General statistical explanation: an ordered scale ranks levels of severity, but the numerical distance between adjacent categories is not necessarily identical in lived or clinical meaning. Treating change in the score as a continuous measure permits mean-based summaries, but the registry record does not report sensitivity analyses using an ordinal method or other outcome scale. The posted means should therefore be understood as summaries on the specified score scale, not as literal units of pigmentation or as a count of severity categories improved for each participant.

11. Confidence Intervals and Precision

The recalculated primary contrast is 0.0, with a 95% confidence interval from -0.708 to 0.708. This interval expresses uncertainty about the difference in mean change between the trifarotene and vehicle arms under the approximate unadjusted calculation. It is centered on the posted contrast and includes values below and above zero.

General statistical explanation: a confidence interval is a range produced by a procedure that, under its assumptions and repeated use, would contain the underlying parameter at the stated rate. For a particular trial, the interval is not a guarantee that the true effect lies within its limits. It is also not a range of individual participant outcomes. The primary interval concerns the difference between arm-level means.

The interval allows for a range of possible between-arm differences rather than supporting a single exact value. Since it includes zero, the result is compatible with no difference under the calculation. Its other values also indicate that nonzero differences remain compatible with the summaries. The interval alone cannot determine whether any such difference would be clinically important; the registry record does not report a threshold for clinical importance or a minimal important difference for this scale.

The arm-level standard errors are 0.27 for trifarotene and 0.24 for vehicle. These are estimates of uncertainty in the respective means, not estimates of participant-to-participant variability. The recalculated contrast and interval rely on posted summaries and an approximate standard deviation. They do not incorporate undocumented modeling or analysis choices. No sponsor-reported confidence interval for the comparison is listed in the registry record.

The displayed precision should not be mistaken for certainty about the underlying effect. The point estimate is equal to zero at the reported precision, but the interval is the more informative description of uncertainty. The appropriate reading is that the registry summaries yield a near-zero unadjusted contrast with uncertainty extending in either direction, not that the two creams have been proven identical.

12. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified as absolute change in PIH ODS score at Week 24, and the record also lists secondary outcomes at Week 24 and earlier visits. The registry record does not report whether a formal multiplicity strategy was used, such as a testing hierarchy or an adjustment for the number of secondary comparisons. It also does not report whether an interim analysis was planned or conducted. These details should not be inferred from the presence of multiple outcomes or from the completed status.

General statistical explanation: when several outcomes or timepoints are examined, the chance of obtaining at least one apparently unusual result can increase if each is tested separately without accounting for the collection of tests. This is why unadjusted secondary findings generally carry less confirmatory weight than a primary result specified in advance and interpreted under a known testing plan. The registry record does not describe the relevant prespecification or testing procedures for this trial.

The primary outcome population is described as the Intent to Treat population, including all randomized participants. That definition identifies who belongs to the target analysis population, but it does not explain how missing Week 24 scores were handled. The registry record does not report the amount or pattern of missing outcome data, reasons for missingness, imputation procedures, or sensitivity analyses. It is also not possible to tell from the record whether every randomized participant contributed an observed value to each posted summary.

General statistical explanation: missing data can affect interpretation when the availability of an outcome is related to participant characteristics or outcomes. Different assumptions and methods for handling missing measurements can produce different estimates. Without details on missingness and analysis procedures, the robustness of the reported means to incomplete follow-up cannot be assessed from the registry record.

The record lists no reported analyses for the outcomes. In consequence, the available summaries do not document a full statistical analysis plan, model specification, multiplicity control, interim monitoring, or missing-data strategy. These absences limit reconstruction of the analysis and should be kept distinct from evidence that a particular procedure was or was not used outside what the registry reports.

13. 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: bipolar disorder (1.6%).

The serious adverse event figures are reported separately for the two arms. In the trifarotene cream arm, 0 of 60 participants were recorded with a serious adverse event; in the vehicle arm, 1 of 63 was recorded with a serious adverse event. The registry lists Bipolar Disorder at 1.6% among the serious-event terms. No deaths are reported in either arm.

The record also reports other, non-serious adverse events for 10 of 60 participants in the trifarotene arm and 19 of 63 participants in the vehicle arm. These figures describe the counts recorded in the registry and should not be conflated with the serious-event counts.

These safety summaries are descriptive. A small number of serious events cannot establish whether an event was caused by an assigned cream, and the registry record does not provide event narratives, timing, severity details beyond seriousness, or an assessment of relatedness. The figures also do not substitute for a complete evaluation of safety across all participants and possible event types. They should be read as the adverse-event counts posted for the trial, not as a recommendation about either intervention.

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

The primary result describes mean change in PIH ODS score from baseline to Week 24 in the two randomized arms. Both posted arm means are -2.1, and the simple unadjusted recalculation gives a between-arm difference of 0.0. The negative mean changes indicate lower PIH severity scores from baseline, according to the registry’s scale description. These observations describe the posted trial results; they do not establish why the scores changed.

The result does not prove that the treatments are equivalent. Equivalence requires a prespecified margin and an analysis designed to test whether the difference is sufficiently small relative to that margin. The registry record does not report such a margin or an equivalence analysis. A confidence interval spanning zero is not, by itself, evidence that all clinically meaningful differences have been excluded.

Nor does the comparison establish that either cream caused the observed within-arm reductions. Both groups were followed in a trial, and the posted summaries do not include a no-treatment comparison. The randomized contrast is informative about the difference between assigned groups under the study design, but interpretation also depends on analysis details that are not reported in the registry record.

The endpoint is a severity score and captures one aspect of acne-associated PIH at a particular follow-up. It does not describe every patient’s experience, the full course of acne, or outcomes beyond those recorded. Mean changes can also conceal variation among participants: some individual scores may have changed more or less than the average, but individual-level distributions are not reported in the registry record.

The secondary results and safety counts add context, but do not resolve these limitations. The numerical secondary information is incomplete across the listed timepoints, and no multiplicity plan is reported. Safety counts are descriptive and do not establish causality. The findings should therefore be understood as registry-reported comparative summaries for this completed study, with uncertainty and unreported analysis details remaining relevant to any broader interpretation.

15. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between observing change within each arm and estimating a contrast between arms. Both groups had the same displayed mean change in the primary score, while the study question concerns whether the assigned creams differed. That distinction prevents the within-arm decreases from being mistaken for a comparative treatment effect.

It also highlights why an estimate should be read alongside its confidence interval. A point estimate of 0.0 is not a complete account of the result: the interval indicates the range of differences compatible with the approximate recalculation and extends in both directions around zero. This supports a cautious reading rather than a conclusion of exact equality.

The trial also demonstrates the limits of registry-level statistical reconstruction. The record gives arm summaries and a recalculable comparison, but does not report the sponsor’s analysis details, model specification, missing-data procedures, or multiplicity strategy. Those omissions matter because the posted least-squares means may be model-based, while the simple recalculation is unadjusted and cannot recover undocumented modeling choices.

Finally, the planning illustrations distinguish trial design from post hoc interpretation. They are based on the observed effect under stated assumptions and are not observed power or the trial’s reported sample-size justification. This distinction is important when considering whether a future study should use a different target effect or design. Overall, the trial offers a useful example of interpreting a null-centered estimate without treating it as proof of no difference and of separating reported details from unanswered methodological questions.

16. 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 main trial-specific limitation for statistical interpretation is the gap between the registry’s outcome summaries and the details needed to reproduce the analysis. Although least-squares means and standard errors are reported, the model, adjustment variables, and estimation procedure are not described in the registry record. The unadjusted recalculation is therefore not interchangeable with a sponsor’s model-based comparison.

The registry identifies the Intent to Treat population as all randomized participants but does not provide a participant flow or explain how missing Week 24 scores were addressed. The counts listed for the outcome do not establish that every randomized participant had an observed endpoint. Without missingness information or sensitivity analyses, the effect of incomplete outcome data cannot be evaluated.

The primary measure is an ordered 9-point severity scale summarized using means. The record does not report a scale-validation discussion, a clinically important difference, or alternative analyses that might assess the result without treating score increments as continuous. The interpretation of the numeric mean difference is consequently limited to the specified score measure.

Only one secondary outcome has numerical summaries in the available registry results, while additional secondary measures and timepoints are listed without numerical results. The record also does not report a multiplicity strategy. This limits assessment of the consistency of findings over time and the confirmatory weight of any separate secondary comparison.

Finally, the registry does not report the protocol’s sample-size justification, an interim analysis plan, detailed adherence information, or the analysis plan. These points are unreported rather than evidence that a particular design or procedure was absent. They constrain how fully the trial’s methods and the robustness of its estimates can be assessed.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: AkLief Evaluation in Acne-induced Post-Inflammatory Hyperpigmentation — NCT05089708.
• Registry record last updated 2023-12-20; status last verified 2023-12.
• Results first posted 2023-12-20.
• 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.

20. Record Summary

The registry record describes NCT05089708, a completed randomized, double-masked, parallel Phase 4 study sponsored by Galderma R&D. It enrolled 123 participants with acne vulgaris and compared trifarotene (CD5789) cream with trifarotene vehicle cream over 24 weeks. The primary outcome was absolute change from baseline in PIH ODS score at Week 24 in the Intent to Treat population.

The reported least-squares mean change was -2.1 in each arm. A simple unadjusted recalculation gives a mean difference of 0.0, with a 95% confidence interval from -0.708 to 0.708 and an unadjusted p-value of 1.0. This is not a sponsor-reported comparison. The record lists additional secondary outcomes, but numerical results are not reported for all listed measures and timepoints.

The registry reports 0 serious adverse events in the trifarotene arm and 1 in the vehicle arm, with no deaths reported. Analysis details, missing-data methods, multiplicity procedures, and the sample-size justification are not reported in the registry record.