AGN-199201 for the Treatment of Erythema With Rosacea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AGN-199201 for the Treatment of Erythema With Rosacea (NCT01735201), a randomized phase 2 study. The primary outcome is Percentage of Participants With at Least a 2-Grade Decrease From Baseline on Both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA).

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel Phase 2 trial sponsored by Allergan. The registry lists an enrollment of 357 and a completed status. The study started in 2012-12, with primary completion in 2013-05. Those dates describe the registry timeline and do not provide details about the duration of follow-up beyond the treatment schedules.

The eight listed groups paired Dose A, Dose B, Dose C, or vehicle with either once-daily or twice-daily application. Each group’s description specifies application to the face for 28 days. This structure allows a reader to distinguish comparisons of dose from comparisons of schedule, while recognizing that the endpoint results needed to make those comparisons are not reported in the registry record.

Randomization assigns participants to study groups by chance; in general, this is intended to limit systematic differences between groups at the outset. Triple masking means the record identifies masking at that level, but does not specify which individuals were masked or how masking was maintained. Further details about the allocation process, concealment, and masking procedures are not reported in the registry record.

The enrollment figure is not a group-by-group accounting of participants, and it should not be used as the denominator for any particular endpoint or safety result. The primary endpoint population is defined separately by treatment exposure and measurement availability. The registry record does not report the number analyzed in each group.

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: 357 patients were randomized; 1 patient in error. 356 patients were included in the Modified intent-to-treat and Safety populations.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified intent-to-treat population included all randomized patients who applied study medication during the study, had both CEA and SSA measurements at Baseline and at least 1 post-baseline measurement for both CEA and SSA.

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.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With at Least a 2-Grade Decrease From Baseline on Both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA), measured over Baseline, Day 28-hours 2 to 12.

The primary endpoint is the percentage of participants with at least a 2-grade improvement from baseline on both the Clinician Erythema Assessment and the Subject Self-Assessment. It was assessed during Day 28 hours 2 to 12. CEA is the investigator’s rating of erythema severity, while SSA is the participant’s rating of unwanted redness. Both assessments use five-point scales running from 0 to 4, with higher scores representing more redness or greater severity.

Requiring improvement on both scales makes this a joint response definition: a participant must meet the threshold on the clinician assessment and on the self-assessment. In general, using two perspectives can describe a response that is evident to both an observer and the participant, although it also means that improvement on only one measure does not meet the endpoint definition. This endpoint is reported as a percentage of participants rather than as an average change in score.

The baseline comparison makes the measure about change within each participant, while the treatment-group comparison would address differences in the proportion meeting the response definition. The registry provides the endpoint definition and its timeframe, but not the group percentages, uncertainty estimates, or statistical comparisons. The observed size and precision of any treatment-group difference are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

A percentage endpoint expresses the share of participants meeting a prespecified condition. Here, that condition is a decrease of at least 2 grades from baseline on both CEA and SSA. In general, a percentage is easy to interpret as a response frequency, but its precision depends on how many participants were assessed and how many met the condition. The registry does not report the endpoint counts or percentages, so neither the response frequency nor its precision can be described for this trial.

Why use both assessments?

CEA is an investigator’s rating, and SSA is the participant’s rating. The combined endpoint requires both perspectives to reach the improvement threshold. In general, combining measures can make a response definition more demanding and can avoid treating a change on just one measure as a joint response. It also means that each participant’s status on both measures is needed to determine whether the endpoint was met. Separate CEA or SSA results would not, by themselves, establish the combined response rate.

What does the scale tell the reader?

The record describes both instruments as five-point scales from 0 to 4. For CEA, the anchors range from clear skin with no signs of erythema to severe, fiery redness. For SSA, they range from clear of unwanted redness to completely unacceptable redness. A decrease is defined as improvement. The endpoint uses a change from baseline rather than an absolute score at Day 28, and requires a decrease of at least 2 grades on each scale. The registry does not report the distribution of baseline scores or follow-up scores.

How should a group comparison be understood?

In general, a randomized comparison of response percentages estimates how often the defined response occurred in each group. A difference in those percentages would describe an absolute contrast in response frequency; an interval around that contrast would indicate the uncertainty compatible with the data under the analysis. The record does not report group response percentages, comparative estimates, confidence intervals, or p-values for the primary endpoint. No direction or magnitude of a group contrast can therefore be stated.

What does the analysis population mean?

The primary population is described as modified intent-to-treat. It includes all randomized patients who applied study medication, had both CEA and SSA at baseline, and had at least one post-baseline measurement for both. This definition retains randomization as an entry condition but adds requirements about treatment exposure and measurement availability. In general, excluding participants without the required measurements can affect how well an analysis reflects all randomized participants, especially if missingness is related to response or tolerability. The number excluded and the reasons for missing measurements are not reported in the registry record.

What is multiplicity?

Multiplicity arises when several outcomes, time points, doses, or comparisons are examined. In general, making many statistical comparisons without a planned approach can increase the chance of at least one apparently unusual result. This trial lists a primary outcome and secondary joint-response outcomes at 0.5 hour and 1 hour post-dose on Day 28, alongside multiple dose and schedule groups. The registry does not report a statistical analysis plan or a multiplicity adjustment, so it is not possible to say how the reported analyses handled the family of potential comparisons. No comparative outcome analyses are listed.

What are planning calculations?

In general, a sample-size calculation uses assumptions about the outcome, allocation, statistical threshold, and effect worth detecting to illustrate how many participants may be needed for a design. The record describes planning assumptions using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the target effect is a stated fraction of the observed effect. Such an illustration is not an observed result and is not the trial’s own design justification. The actual planning values and a trial-specific sample-size justification are not reported in the registry record. A planning calculation should not be interpreted as observed power.

What do the safety counts add?

The safety summary gives, for each listed group, the number at risk and the number affected by serious events, as well as the number at risk and affected by other events. These are descriptive counts. In general, counts can help orient a reader to the number of participants recorded with events, but they do not by themselves establish whether a difference between groups is meaningful. The registry does not provide comparative statistical analyses of these safety figures, and the reported counts should not be combined across groups to create an unreported total.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome: the percentage of participants with at least a 2-grade improvement on both CEA and SSA. It also lists secondary outcomes using that same joint-response criterion at 0.5 hour and 1 hour post-dose on Day 28. Several doses and two schedules were studied, creating multiple possible group contrasts. The record does not state which contrasts were prespecified for formal testing, how multiplicity was addressed, or whether an adjustment was used. Statistical analyses are not listed, so no testing hierarchy or adjusted inference can be described.

The primary analysis population is defined as randomized participants who applied study medication, had baseline measurements on both scales, and had at least one post-baseline measurement on both. That definition identifies who could contribute to the primary endpoint analysis, but the record does not report how many participants qualified in each group. It also does not describe how participants without required follow-up measurements were handled beyond the population definition.

Missing-data methods, reasons for missing measurements, and sensitivity analyses are not reported in the registry record. In general, missing data can affect a response proportion if participants with unavailable measurements differ in their likelihood of meeting the endpoint. Without the number and pattern of missing measurements or an analysis strategy, the robustness of any endpoint estimate cannot be assessed. The registry also does not report whether any interim analyses were planned or performed, or provide the statistical analysis plan.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure congestive (2.3%), chondrocalcinosis pyrophosphate (2.3%), rotator cuff syndrome (2.3%), hypertension (2.3%), cerebrovascular accident (2.2%).

The safety record lists eight treatment groups and gives a number at risk and a number affected by serious events for each. For once-daily groups, the serious-event counts are 0 of 45 for Dose A, 1 of 44 for Dose B, 0 of 44 for Dose C, and 1 of 44 for vehicle. For twice-daily groups, the corresponding counts are 0 of 45, 1 of 45, 0 of 45, and 0 of 44. These are descriptive counts, not estimates of comparative risk with uncertainty intervals.

The record also gives counts for participants affected by other events: 5 of 45, 5 of 44, 1 of 44, and 1 of 44 among the once-daily groups, and 2 of 45, 6 of 45, 7 of 45, and 6 of 44 among the twice-daily groups, in the same dose-and-vehicle order. The safety record lists serious-event terms with percentages: cardiac failure congestive, chondrocalcinosis pyrophosphate, rotator cuff syndrome, and hypertension at 2.3% each, and cerebrovascular accident at 2.2%. The context and denominators for those term percentages are not reported in the registry record.

Deaths are not reported in the registry record. These safety summaries do not provide a statistical comparison, establish causation, or replace the missing primary endpoint results.

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

The record establishes what the trial set out to compare: three AGN-199201 doses, each used once or twice daily, against vehicle on corresponding schedules. It describes randomization, triple masking, the 28-day treatment schedules, and a joint clinician- and participant-rated primary outcome. It also defines a modified intent-to-treat population and gives descriptive safety counts.

Those design details do not show whether the primary endpoint favored any group. The registry record does not report the primary response percentages, group contrasts, confidence intervals, or p-values. It also does not report the secondary response results. Without those results, the size, direction, and precision of any efficacy difference cannot be assessed. The overall enrollment figure cannot substitute for the group-specific endpoint denominators.

In general, a confidence interval describes a range of values compatible with an estimate under the statistical model and data. It helps distinguish a relatively precise estimate from one with substantial uncertainty. No such interval is reported for the primary endpoint. Similarly, statistical significance cannot be inferred from a trial’s randomization, masking, phase, or enrollment alone.

The safety counts document participants affected by serious and other events in each group, but they are descriptive and do not constitute a comparative analysis. The listed serious-event terms and percentages also lack denominator context in the registry record. They should not be treated as proof that an event was caused by a study intervention or as a complete account of safety.

The record supports a description of the research question and the outcomes it intended to evaluate, not a conclusion about efficacy or comparative safety. The registry does not report a sample-size justification, statistical analysis plan, missing-data strategy, or multiplicity procedure. Those omissions limit assessment of how the study was planned and how its results, if available elsewhere, should be interpreted.

13. Why This Trial Matters Statistically

This trial is statistically notable for a design that crossed three doses with two schedules and included a vehicle group for each schedule. Such a structure can address more than one scientific question, including dose-related contrasts and schedule-related contrasts. In general, however, multiple arms also create choices about which comparisons are primary and how uncertainty from multiple testing is handled. The registry does not describe those choices or list analysis results.

The primary outcome is also a joint response definition rather than a single-scale score. It requires at least a 2-grade improvement on both clinician and participant assessments. This makes the estimand—the quantity the study seeks to compare—specific and interpretable, but it depends on paired measurements from both instruments. The endpoint’s analysis population further requires post-baseline measurements on both scales, making the handling and extent of missing data important to interpretation.

The registry gives a completed status and safety counts across the groups, yet does not report the primary or secondary efficacy results. This illustrates a distinction central to trial appraisal: a sufficiently detailed design description is not the same as an available estimate of treatment effect. Without outcome counts and uncertainty, readers cannot assess the size or precision of a comparative response.

Finally, planning illustrations are conceptually different from observed evidence. The record describes assumptions for a planning calculation, but does not report the trial’s own sample-size justification. Any planning value should be read as conditional on its assumptions, not as a measure of the trial’s achieved information or as observed power.

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 largest limitation for interpretation is that the registry record does not report results for the primary endpoint or either secondary outcome. No group-level response proportions, effect estimates, confidence intervals, or p-values are available in the record. As a result, comparative efficacy and precision cannot be evaluated from these entries.

The record reports enrollment of 357 but does not provide group-specific numbers analyzed for the primary outcome. Although it defines the modified intent-to-treat population, it does not report the number meeting that definition in each group or explain the extent and reasons for missing measurements. The missing-data approach and sensitivity analyses are not reported.

Although randomization and triple masking are recorded, procedural details about allocation, concealment, and masking are not reported in the registry record. The statistical analysis plan, sample-size justification, interim-analysis information, and multiplicity approach are also not reported. These omissions prevent assessment of whether the planned analysis corresponds to the listed outcome structure.

The safety record provides affected-participant counts, but no comparative statistical analysis. The context and denominators for the listed serious-event percentages are not reported, and deaths are not reported in the registry record. The record’s completed status does not resolve these gaps in the posted outcome information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: AGN-199201 for the Treatment of Erythema With Rosacea — NCT01735201.
• Registry record last updated 2019-11-18; status last verified 2019-11.
• Results first posted 2014-05-30.
• 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

This completed, randomized, triple-masked, parallel Phase 2 trial enrolled 357 participants and evaluated AGN-199201 Dose A, Dose B, and Dose C against vehicle, with once-daily and twice-daily schedules applied to the face for 28 days. The study started in 2012-12 and reached primary completion in 2013-05.

The primary outcome was the percentage with at least a 2-grade decrease from baseline on both CEA and SSA during Day 28 hours 2 to 12. Secondary outcomes used the same combined criterion at 0.5 hour and 1 hour post-dose on Day 28. Efficacy results and statistical comparisons are not reported in the registry record. The record gives group-level serious and other event counts but does not report comparative safety analyses.