Adapalene-BPO Gel Associated With Doxycycline Hyclate 100 mg in the Treatment of Severe Acne Vulgaris: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adapalene-BPO Gel Associated With Doxycycline Hyclate 100 mg in the Treatment of Severe Acne Vulgaris (NCT00688064), a randomized phase 3 study. The primary outcome is Percent Change From Baseline in Total Lesion Counts at Week 12..

2. Clinical Question

The registry also identifies safety as an aim and lists secondary measures concerning inflammatory and non-inflammatory lesion counts, investigator global assessment success, and adverse events. The central contrast is therefore the addition of active adapalene-BPO gel versus vehicle gel within a regimen that included doxycycline in both groups. The posted record provides arm-level results for the primary measure and a secondary success-rate comparison, but does not report a formal inferential comparison for the primary endpoint. It also does not report a detailed definition of success on the investigator assessment, or additional clinical eligibility criteria. Those omissions limit how specifically the clinical question can be interpreted beyond the registered population, treatments, outcome, and assessment time.

3. Trial Design

This was a randomized, parallel-group Phase 3 trial. The registry lists quadruple masking, but does not specify which roles were masked or how masking was maintained. The two groups received either adapalene-BPO gel with doxycycline or vehicle gel with doxycycline, so the intended contrast concerned the topical gel while the oral treatment was common to both arms.

The registry records enrollment of 459 participants. The posted primary outcome summaries include 232 participants in the adapalene-BPO plus doxycycline group and 227 in the vehicle plus doxycycline group. The study is marked completed. Its recorded start was 2008-08 and its primary completion was 2009-02. The sponsor is Galderma R&D.

The primary endpoint was assessed at week 12. It was the percent change from baseline in total lesion counts, summarized by the median and full range in an ITT, LOCF population. Secondary outcomes include changes in inflammatory and non-inflammatory lesion counts, success on the investigator global assessment, and the percentage of participants with adverse events. The registry lists four secondary outcomes, although its outcome-measure count is five when the primary endpoint is included.

Details such as the randomization method, concealment procedures, masking procedures, protocol deviations, and the planned sample-size justification are not reported in the registry record. No interim analyses or stopping rules are reported in the registry record. Consequently, the design can be described from the listed allocation, masking, model, arms, and endpoints, but not from unreported procedural details.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT, LOCF

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 Percent Change From Baseline in Total Lesion Counts at Week 12., measured over Week 12.

The primary endpoint is the percent change from baseline in total lesion counts at week 12. It describes the relative change in the measured total lesion count from each participant’s starting point, rather than the count at week 12 alone. A negative value represents a decrease from baseline; a positive value represents an increase. The registry reports the median for each group and gives the full range, rather than a mean and standard deviation.

Lesion counts provide a direct measure of the condition being studied. Using change from baseline expresses how counts shifted during the study while accounting for the fact that participants may have started with different counts. The endpoint is measured at a specified follow-up time, so it captures the result at week 12 rather than the course of change across all visits. The registry does not provide a more detailed rationale for selecting this endpoint or a definition of the total lesion-count assessment.

The reported medians are -64.0 for adapalene-BPO plus doxycycline and -41.0 for vehicle plus doxycycline. The respective full ranges are -100.0 to 34.0 and -92.0 to 64.0. These are descriptive arm summaries. No formal inferential comparison for the primary endpoint is reported in the registry record, so the medians and ranges alone do not establish the precision of the between-group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a median and full range for the primary endpoint, while a secondary binary outcome has a posted risk-difference analysis. These summaries answer different questions. The median describes the middle of the observed distribution of participant-level changes; the full range gives the lowest and highest observed values. A risk difference compares the proportions classified as successes in the two groups. General statistical explanations below describe what these measures mean; they do not add unreported details about the trial’s analysis plan.

What does the median summarize?

The median is the value at the center of an ordered set of observations. It is less influenced by very high or very low observations than the arithmetic mean. For a percentage-change endpoint, the median gives a central description of participant-level changes, but it does not show the entire distribution. Two groups can have different medians while their distributions overlap, and a median alone does not quantify the uncertainty of a between-group difference.

The full range records the most extreme observed values in either direction. It is useful for showing the span of the posted outcomes, but it can be strongly affected by a small number of extreme observations. It is not a measure of typical spread in the same way as a standard deviation or interquartile range, and it does not indicate how precisely an estimated group contrast is known.

What does a confidence interval mean?

General explanation: a confidence interval gives a range of values compatible with an estimate under the statistical procedure used. Its width communicates precision: a narrower interval indicates greater precision than a wider one, under the same method and assumptions. It does not mean that a particular proportion of participants had effects inside the interval, and it does not by itself establish clinical importance.

The secondary investigator-assessment result includes a risk-difference estimate and confidence interval. The risk difference is the difference between the observed success proportions, expressed as a proportion. The posted estimate is 0.231. Its interval is above zero, and the unadjusted p-value is < 0.001. The registry does not report an adjustment for testing multiple outcomes, so the confidence interval and p-value should be understood as unadjusted rather than as accounting for all outcome testing.

Why distinguish descriptive and inferential results?

Descriptive statistics report what was observed in the analyzed groups. Inferential statistics use a model or procedure to estimate uncertainty about a contrast beyond those observed participants. The primary endpoint has arm-level medians and ranges, but no formal inferential comparison is reported in the registry record. The secondary success outcome has a posted comparison. The availability of inference for one endpoint does not supply a test or interval for another endpoint.

General explanation: a p-value measures how unusual data at least as incompatible with a null hypothesis would be under the assumptions of a specified test. It is not the probability that the null hypothesis is true, and it is not a measure of the size or clinical importance of an effect. The posted unadjusted p-value for the secondary outcome is evidence about that comparison under its analysis assumptions, not a substitute for an absent primary comparison.

What do the sample-size illustrations mean?

The registry includes planning illustrations computed from the observed secondary effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. They show participants per arm for 80% or 90% power under several stated fractions of that observed effect. These are planning illustrations, not the trial’s original design justification and not observed power. A planning result based on an effect estimated from trial data is conditional on that effect and on the stated assumptions; it does not establish the probability that this completed trial detected an effect.

General explanation: power is the probability that a specified design and analysis would reject a particular null hypothesis if a particular true effect were present, under the assumptions used for planning. It depends on the chosen effect, variability, significance level, allocation, and analysis. It is not a property that can be inferred retrospectively from whether a result was statistically significant. The registry’s planning illustrations should therefore be read as hypothetical design calculations, not as evidence about the trial’s observed ability to detect its primary endpoint.

What is not available for the primary analysis?

The registry identifies the primary population as ITT, LOCF. ITT generally refers to analyzing participants according to their randomized assignment, while LOCF means that a last observed value is carried forward to fill a later missing measurement. These are general definitions; the registry does not describe implementation details, the amount or pattern of missing data, or the reasons for missingness. LOCF relies on assumptions about how an unobserved outcome relates to the last observation, and those assumptions may not hold in every setting.

Because the primary result is reported as arm-level median and full range without a formal contrast, the registry does not give a primary confidence interval, p-value, or adjusted estimate. The analysis method for the secondary binary comparison is not described in detail. The registry record also does not report a protocol-specific sample-size justification, the handling of multiplicity, or sensitivity analyses. These omissions prevent a fuller appraisal of the planned inferential strategy.

10. Multiplicity, Missing Data and Analysis Populations

The primary population is listed as ITT, LOCF. ITT generally preserves the randomized group assignment in analysis, while LOCF uses the last recorded measurement when a later measurement is missing. These labels do not reveal how many participants had missing week 12 measurements, the reasons for missingness, or whether every randomized participant contributed to the posted summaries. Those details are not reported in the registry record.

General explanation: carrying a last observation forward assumes that this value is an acceptable stand-in for the missing later outcome. If outcomes would have continued to change after the last observed visit, the substitution may not represent the unobserved measurement well. Without information about missingness patterns or sensitivity analyses, the effect of this method on the result cannot be assessed from the record.

The registry record does not report a multiplicity adjustment or a hierarchy for testing the primary and secondary outcomes. The secondary investigator-assessment comparison is explicitly unadjusted in the posted analysis. Because the record lists multiple secondary measures, the result should be viewed with caution in the context of multiple testing. No correction should be assumed where none is reported.

The primary endpoint has descriptive summaries but no formal inferential comparison in the registry record. The record does not report a primary p-value, confidence interval, or adjusted contrast. It also does not provide a protocol-specific sample-size justification, a detailed analysis plan, or information about interim analyses. Consequently, the planned relationship between endpoints and inferential testing cannot be reconstructed from the posted record. These missing details affect appraisal of precision, missing-data handling, and the interpretation of the secondary p-value; they do not change the numerical summaries that are posted.

11. 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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each group: 0 among 232 participants receiving adapalene-BPO plus doxycycline and 0 among 227 receiving vehicle plus doxycycline. This states what the record posts for the serious-event counts; it does not establish that the regimens have no serious risks. A count of zero observed events is not proof that an event cannot occur, and the record does not give a confidence interval for these counts.

Deaths are not reported in the registry record. The serious adverse-event terms are also not listed. The registry separately reports 43 other adverse events in the adapalene-BPO plus doxycycline group and 48 in the vehicle plus doxycycline group. These counts are not a comparison adjusted for exposure time or participant characteristics, and the record does not provide further detail about event types, severity, timing, or attribution in the information posted.

Serious and other adverse events are different categories in the record. The serious-event figures should not be combined with the other adverse-event counts or interpreted as a complete account of tolerability. The safety information is limited to the posted counts and does not support broader conclusions beyond those observations.

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

The posted primary summaries show that the median total lesion count change at week 12 was a larger decrease in the adapalene-BPO plus doxycycline group than in the vehicle plus doxycycline group. The full ranges show substantial variation in each group, including participants whose counts increased. Because the registry record does not report an inferential primary comparison, the precision of the primary between-group difference is unknown from these results.

The secondary investigator global assessment comparison reports a higher success proportion in the active-gel group and an unadjusted p-value of < 0.001. This is a result for that secondary outcome, not a test of the primary median endpoint. Its unadjusted status and the absence of a reported multiplicity strategy limit how strongly it can be used to support a broader claim across outcomes.

The trial compares two regimens that both include doxycycline. It does not answer what would happen without doxycycline, and the topical combination does not allow the separate contribution of adapalene and benzoyl peroxide to be distinguished. Results are reported at week 12 and do not establish what happened at other times. The registry also does not report enough detail to assess the impact of missing data, the specific investigator-assessment success definition, or the planned analysis strategy.

These findings are statistical descriptions of the posted trial data, not medical advice. They do not by themselves determine clinical importance, provide a complete safety assessment, or guarantee that the same results would occur in other populations or settings. Interpretation should remain tied to the registered population, the two assigned regimens, the week 12 assessments, and the limitations of the posted analyses.

13. Why This Trial Matters Statistically

This trial illustrates why endpoint summaries and treatment contrasts should be distinguished. A median and range can describe observed outcomes in each group, but they do not by themselves provide an estimate of uncertainty for the between-group difference. The primary endpoint has these descriptive summaries, yet no formal inferential comparison is reported in the registry record. Readers therefore cannot determine from the posted primary results how precisely the groups differ.

It also illustrates why an inferential result for a secondary outcome cannot be substituted for a primary analysis. The investigator global assessment comparison has a posted risk difference, confidence interval, and unadjusted p-value, while the primary lesion-count result does not have a posted contrast. Their directions are consistent, but their definitions and analytical status differ. Keeping that distinction clear prevents a secondary result from being mistaken for a formal test of the primary endpoint.

The record also highlights the importance of multiplicity and missing-data reporting. Several secondary outcomes are listed, yet adjustment for multiple testing is not reported. The primary population uses ITT, LOCF, but the record does not describe missingness or sensitivity analyses. Those details matter when judging the reliability and scope of an estimate, even when descriptive values are available.

Finally, the sample-size illustrations are based on the observed effect and stated assumptions, rather than a reported original design justification. Their role is planning, not evidence of observed power. These features make the study a useful example of how registry results can contain informative arm-level and secondary summaries while still leaving important questions about primary inference and analysis planning unanswered.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint is reported only through arm-level medians and full ranges. A formal between-group estimate and its uncertainty are not reported in the registry record. This limits statistical interpretation of the principal outcome, even though the direction of the two medians can be described. The ranges also do not show the distribution’s shape or provide a measure of uncertainty for the median.

The primary population is identified as ITT, LOCF, but the record does not report how many participants had missing observations, the reasons for missingness, or sensitivity analyses using other approaches. The endpoint description does not provide a detailed lesion-count assessment procedure. These omissions make it difficult to judge how the analysis population and missing-data method affected the reported summaries.

Only one secondary outcome has a posted inferential comparison. The result is unadjusted, and multiplicity handling is not reported. The registry lists other secondary measures but does not provide their detailed results in the posted analyses. The investigator global assessment success definition is also not reported, limiting interpretation of precisely what qualified as success.

The safety record gives serious-event counts but does not list serious-event terms or report deaths. Other adverse events are counted, but the registry does not provide further detail about their nature or timing in these results. The record also lacks a detailed protocol-specific sample-size justification, analysis plan, and information about interim analyses. Finally, both groups received doxycycline, and the active topical regimen combines adapalene with benzoyl peroxide. The design as posted does not isolate the separate effects of those components or estimate the effect of doxycycline versus no doxycycline.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Adapalene-BPO Gel Associated With Doxycycline Hyclate 100 mg in the Treatment of Severe Acne Vulgaris — NCT00688064.
• Registry record last updated 2021-02-18; status last verified 2010-03.
• Results first posted 2010-03-31.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT00688064 is a completed, randomized, parallel-group Phase 3 trial sponsored by Galderma R&D. It enrolled 459 participants with severe acne vulgaris and lists quadruple masking. The recorded start was 2008-08, and primary completion was 2009-02.

The comparison was adapalene 0.1% / benzoyl peroxide 2.5% gel plus doxycycline hyclate 100 mg tablets versus vehicle gel plus doxycycline hyclate 100 mg tablets. The primary endpoint was median percent change from baseline in total lesion counts at week 12 in an ITT, LOCF population, with the full range reported for each group.

The registry posts primary arm summaries and one secondary investigator-assessment success comparison. It does not report a formal inferential comparison for the primary endpoint. Serious adverse events are recorded as zero in both groups; deaths are not reported in the registry record. Multiplicity handling, detailed missing-data information, and a protocol-specific sample-size justification are not reported in the registry record.