Study to Evaluate Safety & Efficacy of Sarecycline in Treatment of Acne: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Safety & Efficacy of Sarecycline in Treatment of Acne (NCT02320149), a randomized phase 3 study. The primary outcome is Absolute Change in Facial Inflammatory Lesion Counts at Week 12.

2. Clinical Question

The primary endpoint focuses on inflammatory lesions, including papules, pustules, and nodules as defined in the registry record. Counts were assessed across facial areas including the forehead, cheeks, nose, and chin. The trial also registered outcomes relating to percent change and other time points, but the primary statistical question is the Week 12 comparison in absolute change.

This is a comparison between assigned treatment groups, not a comparison of each participant with an untreated counterfactual. The posted results describe group-level changes and an adjusted group contrast. They do not by themselves establish why any individual participant's lesion count changed, nor do they address acne outcomes beyond those recorded in the trial.

3. Trial Design

The registry describes a randomized, double-blind, placebo-controlled, parallel-group Phase 3 study. Participants were assigned to oral sarecycline or matching placebo, with once-daily dosing over 12 weeks. The registry record lists acne vulgaris as the condition and describes the target population as people with moderate to severe facial acne vulgaris.

The randomized design supports a comparison between groups formed by treatment assignment. Double masking is intended to reduce the influence of knowledge of assignment on participant experience, clinical assessment, and trial conduct. The registry does not specify who was masked beyond the overall double-masking designation, so further details about the masking arrangements are not reported in the registry record.

Enrollment was 968. The primary analysis used the ITT population, defined in the record as all randomized participants. The arm-level primary outcome summaries list 483 participants in the sarecycline group and 485 in the placebo group. These endpoint analysis counts should be read as the counts associated with the posted summaries; the handling of participants with missing Week 12 measurements is not reported in the registry record.

The primary endpoint was absolute change in facial inflammatory lesion counts from baseline (Day 1) to Week 12. The registry identifies ANCOVA as the analysis method, with treatment group and pooled study center as factors and baseline value as a covariate. Secondary outcomes include percent change in inflammatory lesion counts at several visits and measures of noninflammatory lesions. The registry record does not report the original sample-size justification, intended effect size, or planned analysis details beyond the endpoint-specific information recorded.

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 population included all randomized participants.

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: Intent-to-treat (ITT) Population included all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Absolute Change in Facial Inflammatory Lesion Counts at Week 12, measured over Baseline (Day 1) to Week 12.

The primary endpoint is the absolute change in facial inflammatory lesion count between baseline (Day 1) and Week 12. Counts covered the forehead, left and right cheeks, nose, and chin. Inflammatory lesions were defined as papules, pustules, and nodules, using the size and appearance criteria stated in the registry record. The endpoint is continuous: it records a count-based change rather than a yes-or-no outcome.

A negative change means that the count decreased from baseline. The reported group estimates were -15.3 for sarecycline and -10.1 for placebo, each expressed as a least-squares mean. The reported adjusted difference, sarecycline relative to placebo, was -5.2 lesions. Its negative direction indicates a larger average decrease in the sarecycline group under the stated contrast.

Using change from baseline makes the outcome interpretable in relation to participants' starting counts. The registry's ANCOVA model also included baseline value as a covariate, which accounts for baseline measurements in estimating the treatment-group contrast. This endpoint was selected as the primary measure for the trial's Week 12 comparison. It captures change in the specified facial inflammatory lesion count; it does not represent every feature of acne, participant experience, or safety.

7. Results Posted in the Registry

• Sarecycline: mean -15.30 versus -10.10 on control; difference -5.20 (95% CI -6.86 to -3.54), standardized effect d = -0.39; z-test p = <0.001.

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 Facial Inflammatory Lesion Counts at Week 12

• 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:
  • Sarecycline: mean -51.80 versus -35.10 on control; difference -16.70 (95% CI -22.11 to -11.29), standardized effect d = -0.39; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Sarecycline than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 9

• 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:
  • Sarecycline: mean -47.40 versus -34.90 on control; difference -12.50 (95% CI -17.21 to -7.79), standardized effect d = -0.33; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Sarecycline than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 6

• 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:
  • Sarecycline: mean -42.20 versus -28.90 on control; difference -13.30 (95% CI -17.73 to -8.87), standardized effect d = -0.38; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Sarecycline than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary results reported for inflammatory lesion counts at Week 6, Week 9, and Week 12 show negative group estimates and negative between-group contrasts. For a change measure, negative values indicate decreases from baseline. The direction across these reported visits is consistent with the primary Week 12 result: the estimates indicate larger decreases in the sarecycline group than in the placebo group under the stated comparisons.

These results add temporal context to the primary endpoint by showing that the direction of the inflammatory-lesion comparisons is present at the reported intermediate visits as well as at the primary visit. They do not establish that the change followed a particular trajectory between assessments, and they should not be interpreted as independent replications: the measures are related outcomes collected within the same trial.

The registry lists secondary outcomes covering percent change, other visits, absolute change, and noninflammatory lesion counts. Fifteen secondary results are posted. The record does not provide enough detail to treat every listed outcome as having the same statistical status or to infer the results of measures not described in the available analyses. The overall pattern should therefore be stated narrowly: the reported inflammatory lesion comparisons at the listed visits have a consistent direction with the primary comparison.

Secondary findings generally carry less confirmatory weight than the primary endpoint when many outcomes or time points are examined. Each additional comparison creates more opportunities for an apparently notable result, unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity-adjustment strategy. As a result, unadjusted secondary p-values should be interpreted cautiously and as supportive context rather than treated as if each were an independently confirmed primary finding. This caution does not change the direction of the posted estimates; it affects how strongly their statistical significance can be interpreted across the collection of outcomes.

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

• Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 12
• Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 9
• Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 6
• Percent Change From Baseline in Facial Inflammatory Lesion Counts at Week 3
• Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 9
• Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 6
• Absolute Change From Baseline in Facial Inflammatory Lesion Counts at Week 3
• Percent Change From Baseline in Facial Noninflammatory Lesion Counts at Week 12

9. Statistical Interpretation

10. Statistical Methods Explained

The primary analysis is described as an analysis of covariance, or ANCOVA. In general, ANCOVA compares outcome levels or changes between treatment groups while including one or more covariates in a statistical model. Here, the registry states that treatment group and pooled study center were factors and baseline value was a covariate. This means the reported treatment contrast accounts statistically for baseline lesion count and study center, rather than relying only on a raw subtraction of the two posted group means.

The reported endpoint estimates are least-squares means. In general, a least-squares mean is a model-based group estimate adjusted for the other terms in the model. It is not necessarily identical to an unadjusted arithmetic average. The registry's arm summaries report -15.3 for sarecycline and -10.1 for placebo, and the reported ANCOVA least-squares mean difference is -5.2. The model's contrast is the central comparison: it expresses the estimated difference between the groups in the direction sarecycline relative to placebo.

The sign needs to be interpreted in light of the endpoint definition. Negative change indicates fewer inflammatory lesions than at baseline. Thus, a negative between-group difference means a larger decrease in the sarecycline group than in the placebo group, according to the stated contrast. The sign does not mean a negative count, and it does not imply that every participant had a decrease.

The reported 95% confidence interval for the primary difference runs from -6.7 to -3.6. In general, a confidence interval gives a range of values compatible with the data and the statistical model, under the method's assumptions. Its width conveys uncertainty: a narrower interval indicates greater precision than a wider interval, all else equal. An interval is not a range containing every individual response, nor does it assign a probability to the fixed treatment effect after observing the data.

The sponsor-reported p-value is p < 0.001. In general, a p-value measures how unusual data at least as incompatible with a null hypothesis would be if that null and the test assumptions held. It is not a measure of clinical importance or a direct probability that the finding is due to chance. The registry classifies the reported analysis as a superiority analysis. That label describes the statistical comparison being made; the numerical estimate, confidence interval, and model context are needed to understand the direction and precision.

A separate recalculation uses posted summary statistics to estimate an unadjusted mean difference and confidence interval. Such a recalculation is not the same as the sponsor's ANCOVA: it does not reproduce the baseline and pooled-center adjustment from individual participant data. The group standard errors are reported as 0.6 for each arm, and the recalculation uses an approximate pooled standard deviation. That approximation is useful for a summary-based comparison, but it cannot reconstruct every feature of the original model or its covariance structure. The recalculated estimate is -5.2, with a confidence interval from -6.863 to -3.537 and p < 0.001. Its agreement in direction and rounded point estimate with the reported result is reassuring as a check, while the sponsor's model-based result remains the trial's reported analysis.

Standard errors describe the estimated sampling variability of a statistic, not the spread of individual participant outcomes. The registry lists standard errors of 0.6 for the group least-squares means. They support estimation of uncertainty around the group means and contrasts. They should not be interpreted as standard deviations or as the amount of change experienced by a typical participant.

What does the adjusted comparison account for?

The baseline covariate represents the starting lesion count, while pooled study center accounts for the study-center grouping used in the model. Adjusting for these terms can improve comparability of estimated outcomes when baseline values or centers are related to the endpoint. Random assignment provides the foundation for the treatment comparison; model adjustment is an additional statistical step. The registry does not give further details on the coding of center, model diagnostics, or handling of missing covariate or outcome values.

What do the power illustrations mean?

In general, power is the probability that a specified statistical test will reject its null hypothesis under a particular assumed effect and analysis setup. The planning illustrations use the observed effect or stated fractions of it, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The figures are participants per arm. They are hypothetical planning calculations, not a description of the trial's original design rationale and not observed power. The original sample-size assumptions are not reported in the registry record.

The calculations use an observed summary contrast and therefore inherit its uncertainty. Planning for a smaller effect requires more participants, because a smaller separation between group means is harder to distinguish from sampling variation. These illustrations can show how sample-size requirements change under the stated assumptions, but they do not establish the sample size that would be appropriate for a different population, endpoint, allocation, or analysis. They also do not incorporate details that are not listed in the planning assumptions.

The statistical interpretation depends on the design and analysis population as well as the numerical result. The record identifies all randomized participants as the primary ITT population. It does not report the extent of missing Week 12 outcomes or the method used for any missing values, so the influence of missing data on the model-based estimates cannot be assessed from the registry record alone. Multiplicity handling across secondary endpoints is also not reported. Consequently, the primary endpoint's reported inference should be distinguished from exploratory or unadjusted inferences across multiple outcomes.

11. Confidence Intervals and Precision

The sponsor-reported primary comparison is -5.2 lesions, with a 95% confidence interval from -6.7 to -3.6. The interval is entirely negative, matching the direction of a greater decrease in the sarecycline group under the stated contrast. The range gives a sense of the precision of the adjusted estimate: values near either endpoint are compatible with the observed data under the model and its assumptions, while values outside the interval are less compatible at the stated confidence level.

The interval should not be read as the range of individual participant changes. It concerns uncertainty in the estimated group contrast. Individual changes can vary more widely, and the registry record does not report a distribution of individual responses in these results. The reported standard errors of 0.6 for the arm estimates are also measures of uncertainty in estimated means, not measures of participant-to-participant variability.

The summary-based recalculation gives a confidence interval from -6.863 to -3.537. This interval is based on an unadjusted approximation from posted summary statistics, rather than the sponsor's ANCOVA model. It is close in direction and overall scale to the sponsor-reported interval, but the methods differ. The adjusted interval is the relevant one for the reported ANCOVA analysis; the recalculated interval serves as a supplementary check rather than a replacement.

Confidence intervals communicate precision, not importance. Whether a difference of the estimated size is meaningful for patients is not established by interval exclusion of zero alone. The registry record does not report a threshold for clinical importance. The interval also does not account for uncertainties that may arise from unreported missing-data or multiplicity procedures.

12. 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 are participants per arm, not total participants and not total events. They illustrate sample sizes under a normal approximation, two-sided significance level 0.05, and equal allocation between the two arms. The calculation uses the observed effect as its reference and also considers planning for 75% of the observed effect and 50% of the observed effect. These are planning illustrations based on the observed results; the trial's own original design assumptions are not reported in the registry record.

The 80% power column gives the estimated participants per arm under the stated assumptions for a design with 80% power to detect the effect used in that row. The 90% power column gives the corresponding per-arm requirement for 90% power. In general, higher planned power means a greater chance of detecting the specified effect if that effect is present, and it usually requires a larger sample under otherwise similar assumptions.

The rows represent different effect sizes relative to the observed effect. Planning for 75% of the observed effect or 50% of the observed effect assumes a smaller difference between groups than planning for 100% of the observed effect. Smaller effects are harder to detect, so they require more participants under the same design assumptions. The curve conveys this relationship across the considered effects; it should be read as a planning aid, not as a summary of what happened during enrollment.

These figures are not observed power. They are calculations made from the observed effect and stated assumptions, and they do not describe the trial's original sample-size rationale. The registry record does not report that rationale or its design assumptions. The figures should therefore be read as hypothetical planning illustrations rather than as evidence that the trial was designed around these estimates.

13. 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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -5.200; pooled standard deviation σ = 13.200.
2. n = 2 × (1.96 + 0.842)² × 13.200² / -5.200² = 101.2, rounded up to 102 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
delta <- -5.2                      # observed difference in means
sigma <- 13.2000282326067                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2320149)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 102 (80% power), 136 (90% power)
 75% of observed effect: n per arm = 180 (80% power), 241 (90% power)
 50% of observed effect: n per arm = 405 (80% power), 542 (90% power)
power.t.test: 102.1 
Simulated power at n = 102 per arm: 0.803 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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.

14. Analyses Reported by the Sponsor

The sponsor-reported primary analysis used ANCOVA and gave a least-squares mean difference of -5.2, a 95% confidence interval from -6.7 to -3.6, and p < 0.001. This is the analysis reported by the registry for the primary endpoint and is the principal model-based result to interpret.

The supplementary recalculation from posted summary statistics also gives an estimated difference of -5.2. Its confidence interval is from -6.863 to -3.537, with p < 0.001. This calculation is unadjusted and uses an approximate pooled standard deviation; it does not reproduce the sponsor's ANCOVA adjustment for baseline value and pooled study center. Differences in the interval endpoints and p-value reflect the distinct calculation and precision conventions, not a separate trial result.

The estimates agree in direction and rounded point estimate, and the sponsor analysis reports a confidence interval that is also entirely negative. The recalculation is a useful check on the posted summary statistics, but it is not a replacement for the trial's ANCOVA analysis. The registry record does not flag a discrepancy between the reported analysis and the recalculation.

15. Multiplicity, Missing Data and Analysis Populations

The primary analysis population is identified as the ITT population, which included all randomized participants. This clarifies the intended population for the primary endpoint comparison. The registry record does not describe whether all randomized participants contributed an observed Week 12 value, how missing outcome measurements were handled, or whether imputation or another missing-data method was used. The extent and possible influence of missing data therefore cannot be evaluated from the record.

Missing data matter because a model-based comparison can be affected when outcome availability is related to treatment assignment, baseline characteristics, or the unobserved outcome itself. In general, the consequences depend on both how much information is missing and why it is missing. Without information on missingness and the analysis procedure, it is not possible to determine whether the reported estimates would change under alternative assumptions about absent measurements.

The record reports multiple secondary outcomes and analyses. It does not report whether statistical testing across those outcomes was adjusted for multiplicity, or whether a hierarchy of tests was planned. When multiple hypotheses are tested, the chance of at least one small p-value can rise if no adjustment or prespecified testing strategy is used. Thus, secondary p-values should not automatically be read with the same confirmatory force as the primary analysis.

The primary endpoint analysis is described as ANCOVA with treatment group and pooled study center as factors and baseline value as a covariate. Additional details such as model diagnostics, assumptions checks, sensitivity analyses, and interim-analysis plans are not reported in the registry record. The registry also does not report the original sample-size justification or the assumptions used in trial planning. These are limits on what can be assessed from the posted record, rather than evidence that a particular procedure was or was not performed.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: abortion spontaneous (0.4%), alanine aminotransferase increased (0.2%), aspartate aminotransferase increased (0.2%), gamma-glutamyltransferase increased (0.2%), diabetic ketoacidosis (0.2%).

The registry reports serious adverse events for the safety populations. In the sarecycline group, 3 serious adverse events were reported among 481 participants at risk; in the placebo group, 5 were reported among 483 participants at risk. The record reports 0 deaths in each group. No other adverse events are listed as affected participants in the reported summary.

The serious adverse event terms listed include Abortion spontaneous at 0.4%, and Alanine aminotransferase increased, Aspartate aminotransferase increased, Gamma-glutamyltransferase increased, Diabetic ketoacidosis, and Nephrolithiasis at 0.2% each. These are registry-reported terms and percentages. They describe reported serious events, not necessarily events judged to be caused by study treatment.

These figures should be read as counts and reported percentages within the stated safety summaries. The at-risk counts differ from the primary endpoint arm counts, so the safety summary and efficacy analysis should not be treated as having identical analysis populations. The registry record does not establish comparative causation from these counts alone, and the absence of reported deaths does not summarize all possible safety outcomes or longer-term risk.

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

The primary result describes a model-adjusted difference between the randomized groups in change in facial inflammatory lesion counts from baseline to Week 12. The estimate is -5.2 lesions for sarecycline relative to placebo, with a sponsor-reported 95% confidence interval from -6.7 to -3.6. Given the endpoint's sign convention, this indicates a greater estimated decrease in the sarecycline group. The result is statistically distinguishable from a zero difference under the reported ANCOVA analysis, which gave p < 0.001.

That finding is specific to the measured endpoint, the study population, the 12-week treatment period, and the analysis described in the registry. It does not establish that every participant had a decrease, or that the group difference was the same for every participant. A group mean cannot describe the full distribution of individual changes.

The result does not by itself establish how large a change would matter to participants. The registry record does not report a threshold for clinical importance or patient-reported outcomes that would translate the lesion-count difference into a broader measure of benefit. Statistical evidence against a zero difference and clinical importance are related but distinct questions.

The posted comparison also does not establish longer-term effects after the treatment period, outcomes for acne features outside the endpoint definition, or effects in populations beyond the trial's stated focus. It does not resolve uncertainty about unreported missing-data methods or multiplicity procedures. Safety interpretation likewise requires care: the serious-event counts are descriptive registry summaries and do not alone establish whether an event was caused by treatment.

Accordingly, the most direct conclusion is about the relative Week 12 change in the specified inflammatory lesion count under the reported randomized comparison and ANCOVA model. Broader claims about overall experience, durability, or individual response are not established by this endpoint alone.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be interpreted through its endpoint, contrast, and analysis model rather than by comparing two group estimates without context. Both group mean changes are negative, but the central statistical question is the between-group difference. The ANCOVA estimate is adjusted for baseline lesion count and pooled study center, and its negative sign indicates a greater modeled decrease in the sarecycline group under the stated contrast.

The distinction between model-based and unadjusted estimates is also instructive. The sponsor's ANCOVA and the summary-based recalculation give the same rounded point estimate, while their confidence intervals and p-values differ because the recalculation does not reproduce the trial's adjustment. Similar point estimates do not make methods interchangeable; the reported model and its assumptions remain important to interpretation.

The record also illustrates the difference between precision and clinical importance. The confidence interval conveys uncertainty in the estimated group contrast, while a separate clinical threshold would be needed to interpret whether that contrast is meaningful in practice. No such threshold is reported in the registry record.

Finally, secondary outcomes and safety summaries require context. Related outcomes across visits can support a coherent descriptive pattern, but multiple unadjusted tests carry less confirmatory weight than the primary analysis. Serious adverse event counts describe reported events but do not prove causation. Taken together, the statistical reading depends on separating what the randomized comparison estimates from questions the posted record does not resolve.

19. 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 registry record does not report the original sample-size justification or the assumptions used when planning enrollment. The sample-size illustrations based on the observed effect are not a substitute for that design rationale. It is also not reported whether interim analyses were planned or conducted.

Information about missing Week 12 outcomes and their handling is not reported. Although the primary population is identified as ITT, the record does not describe the number of missing measurements, the assumptions made about them, or sensitivity analyses. These omissions limit assessment of the robustness of the primary estimate to missing-data choices.

The primary ANCOVA specification is described at a high level, but additional details are not reported, including diagnostics, model-assumption checks, and sensitivity analyses. The summary-based recalculation uses approximate dispersion derived from the posted summaries and is not equivalent to an individual-level reanalysis. Its agreement in direction does not remove uncertainty about model details.

The registry lists many secondary outcomes, but multiplicity handling is not reported. Consequently, secondary statistical evidence cannot be interpreted as fully confirmatory without further information about prespecified testing procedures. The available pattern across inflammatory lesion visits is supportive context, not an answer to every listed outcome.

The primary endpoint captures facial inflammatory lesion counts over the treatment period. It does not on its own represent noninflammatory lesions, all aspects of acne, patient experience, or outcomes after treatment. The record also does not provide a clinical-importance threshold for the observed difference. Safety summaries are limited to the reported serious-event counts and terms, and do not establish causality or provide a complete assessment of all potential harms.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study to Evaluate Safety & Efficacy of Sarecycline in Treatment of Acne — NCT02320149.
• Registry record last updated 2019-02-15; status last verified 2019-01.
• Results first posted 2018-05-17.
• 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.

23. Record Summary

NCT02320149 is a completed randomized, double-blind, parallel-group, placebo-controlled Phase 3 study sponsored by Almirall, S.A. It evaluated oral sarecycline at 1.5 mg/kg/day against matching placebo, taken once daily for 12 weeks, for moderate to severe facial acne vulgaris. Enrollment was 968.

The primary endpoint was absolute change in facial inflammatory lesion counts from baseline to Week 12. The reported ANCOVA least-squares mean difference was -5.2 lesions, with a 95% confidence interval from -6.7 to -3.6 and p < 0.001. The estimate indicates a greater decrease in the sarecycline group under the stated comparison.

The primary population was ITT, including all randomized participants. The registry does not report the original sample-size rationale, missing-data handling, or multiplicity strategy. Serious adverse event summaries report 3 events among 481 at risk in the sarecycline group and 5 among 483 at risk in the placebo group; 0 deaths were reported in either group.