Pharmacokinetics and Safety of MM36 Topical Ointment in Pediatric Subjects With Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics and Safety of MM36 Topical Ointment in Pediatric Subjects With Atopic Dermatitis (NCT02945657), a na phase 2 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax) of MM36.

2. Clinical Question

3. Trial Design

This completed Phase 2 study evaluated topical MM36 ointment in pediatric subjects with atopic dermatitis. Its official title describes a multicenter, open-label study under maximal-use conditions. The registry identifies the design as single-group, with no masking and allocation listed as not applicable. The intervention was MM36 topical ointment, 1%, applied twice daily for 28 days. Enrollment was 32.

The study's stated purpose was to assess pharmacokinetic parameters and safety. Its primary outcome focused on maximum observed plasma concentration of MM36 on Day 1. The specified sampling schedule included a pre-dose measurement and measurements at 1, 4, and 8 hours post-dose. The primary pharmacokinetic population included participants in the Safety Population with pharmacokinetic data.

The registry lists safety outcomes that include treatment-emergent adverse events and serious adverse events, adverse events according to severity, application-site adverse events, and clinically meaningful changes in laboratory tests, vital signs, and ECG measures. Some ECG outcomes are specified for different study days. The registry lists 14 outcome measures and 0 analyses. These entries describe the outcomes and analysis records registered, but the primary Cmax summary statistics and detailed results for most safety outcomes are not reported in the registry record.

The study began in 2016-10, reached primary completion on 2017-06-08, and is listed as completed. No randomized comparator is described, so its design supports description of pharmacokinetic and safety observations within the treated study group, not a controlled estimate of treatment differences. Further details about the protocol's statistical plan, sample-size justification, and handling of interim analyses are not reported in the registry record.

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: Pharmacokinetic (PK) population included participants in the Safety Population with PK Data

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 Maximum Observed Plasma Concentration (Cmax) of MM36, measured over Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 1.

The primary endpoint is the maximum observed plasma concentration, or Cmax, of MM36 on Day 1. It is a continuous pharmacokinetic measure expressed in ng/mL. The registry specifies that the reported summary parameter is the mean and that dispersion is described by the standard deviation. Measurements were scheduled before dosing and at 1, 4, and 8 hours post-dose on Day 1.

As a general statistical concept, Cmax describes the highest concentration observed within a defined sampling schedule. It can help characterize the peak systemic concentration after a dose, which is relevant when assessing whether a topical medicine is measurable in plasma under the conditions studied. Its interpretation depends on the timing and completeness of sampling: a maximum observed at scheduled collection times is not necessarily the same as a continuously observed biological peak.

Cmax is not a direct measure of the total amount of drug exposure over time; other pharmacokinetic measures address different aspects of concentration over time. Nor does Cmax alone establish a clinical benefit or determine safety. The registry record does not report the mean Cmax, its standard deviation, individual measurements, or a confidence interval. It therefore describes the endpoint and measurement schedule, but does not allow readers to assess the observed concentration level or its precision from the primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: plasma concentration of MM36, expressed in ng/mL. The registry specifies the mean as the summary parameter and the standard deviation as the measure of dispersion. In general, the mean describes the arithmetic center of a set of measurements, while the standard deviation describes how spread out measurements are around that mean. These summaries answer different questions; a mean alone does not show how variable individual observations were.

The sampling schedule is part of the endpoint definition. The registry specifies a pre-dose measurement and post-dose measurements at 1, 4, and 8 hours on Day 1. The maximum observed concentration refers to the largest value observed within that scheduled set for a participant. In general, more widely spaced sampling can miss a peak that occurs between collection times. The registry record does not report additional sampling times, individual concentration profiles, or the numerical Cmax summary.

What does a confidence interval add?

As a general statistical explanation, a confidence interval communicates uncertainty around an estimated quantity. It can help distinguish a precise estimate from one that remains compatible with a broad range of values. The registry record does not report a confidence interval for the primary Cmax outcome, so the precision of that estimate cannot be judged from the recorded result. The standard deviation, if reported, would describe variability among observations, not by itself the uncertainty around the mean.

How should the single-group design shape interpretation?

A single-group study can describe measurements and events observed among participants receiving the intervention. It does not, by itself, estimate what would have happened to similar participants under a different treatment or no treatment. Randomized comparative designs can support that kind of contrast by assigning participants to different conditions; this study's allocation is listed as not applicable and its model as single-group. Accordingly, no between-group effect should be inferred from this record.

The study is open-label, with masking listed as none. In general, lack of masking can affect assessments that involve judgment or reporting, although the degree of concern depends on the outcome and how it is measured. Plasma concentration is a laboratory-based measure, while adverse-event reports and assessments can involve participant or investigator judgment. The registry record does not describe safeguards, blinded laboratory procedures, or other methods for limiting assessment influence.

What do the safety counts represent?

The record lists 31 at risk for serious adverse events and 0 affected, as well as 31 at risk for other adverse events and 7 affected. It also lists 0 deaths. These are descriptive safety data. They do not establish that the treatment caused or did not cause an event, and the recorded categories do not supply event-level detail. In general, counts observed in a study group have uncertainty, especially when the events of interest are uncommon. A zero count is not evidence that the underlying risk is exactly zero.

Over-dispersion is a general concern when count data vary more than a simple statistical model expects. If safety events were modeled as counts, a method that allows extra variability might be appropriate in some settings. But the registry record does not report a count model, an over-dispersion assessment, or inferential safety estimates. It would therefore be inappropriate to attribute a particular count-data method to this study.

What do the planning assumptions mean?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It specifies that the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, the illustrations are expressed as participants per arm; time-to-event illustrations use a total number of events. These are planning assumptions, not features of the study's single-group design. No resulting planning estimates are reported in the registry record. Such illustrations are not observed power and do not show that the trial had a particular probability of detecting an effect.

The registry record does not report the study's own sample-size justification, the statistical analysis plan, an interim analysis plan, or the inferential method used for Cmax. The sample-size assumptions attached to planning illustrations should not be mistaken for the protocol's design rationale. Nor should the absence of a recorded analysis be taken to mean that no analysis occurred outside the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("MM36 Topical Ointment, 1%")
n   <- c(31)
m   <- c(23.1)
sp  <- c(23.4)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  MM36 Topical Ointment, 1%  31  23.100  23.400  14.517  31.683

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures across pharmacokinetic and safety topics and 0 analyses. Outcomes include the primary Cmax measure, several adverse-event categories, and clinically meaningful changes in laboratory, vital-sign, and ECG measures. The registry record does not state whether these outcomes were treated as confirmatory or exploratory, which analyses were prespecified, or whether any adjustment for multiple testing was planned.

As a general statistical principle, examining many outcomes can increase the chance that at least one result appears notable by chance. Multiplicity procedures can address that issue, but the appropriate approach depends on the study questions and analysis plan. No such procedure is reported in the registry record. Since the primary numerical result is also not reported, the record does not support evaluating statistical significance across endpoints.

Missing-data methods are not reported in the registry record. It does not describe whether any Cmax measurements were missing, how incomplete profiles were handled, or how missing safety information was treated. The primary population is described as participants in the Safety Population with PK Data, but its size and the criteria for the Safety Population are not reported in the registry record. This definition indicates that pharmacokinetic analyses were tied to available PK data, but does not establish how missingness was addressed.

These gaps matter because the analyzed population and missing-data approach can affect both estimates and their interpretation. No assumptions about the reason for missing data, imputation, exclusions, or sensitivity analyses can be made from the registry record.

12. 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 non-serious adverse event terms

The registry record lists 0 serious adverse events among 31 at risk, 0 deaths, and 7 affected in the other-adverse-event category among 31 at risk. These counts are descriptive, not comparative. The study has no concurrent control group, so the figures do not estimate a difference in safety outcomes between MM36 and another treatment.

The record lists additional safety outcomes by severity and for application-site events, as well as laboratory, vital-sign, and ECG changes. The detailed numerical results for these outcomes are not reported in the registry record. Specific terms for the 7 other adverse events are also not reported in the registry record, so their nature and clinical context cannot be characterized from the recorded information.

In general, a zero count means that no event was recorded in the observed group; it does not establish that the event is impossible or that the underlying risk is zero. A study's ability to characterize uncommon harms depends on the amount and duration of observation and the quality of event ascertainment. The registry record does not provide enough detail to quantify uncertainty around these safety counts or to draw conclusions about risks outside the study conditions.

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

This record describes a completed, open-label, single-group study of topical MM36 ointment, 1%, applied twice daily for 28 days in pediatric subjects with atopic dermatitis. Its primary pharmacokinetic endpoint was maximum observed plasma concentration on Day 1, with measurements scheduled before dosing and at 1, 4, and 8 hours post-dose. The registry also records safety outcomes and gives descriptive counts for serious and other adverse events.

The record does not report the primary Cmax mean or standard deviation. It therefore does not establish the observed plasma concentration level or its variability. The recorded safety counts describe events in the study group, but do not show whether MM36 caused those events or how its safety compares with another treatment. The entries also do not establish that no unrecorded event occurred.

As a general distinction, pharmacokinetic measurements describe drug concentrations, while clinical outcomes address effects on health. A concentration result alone does not establish clinical benefit. Likewise, a single-group safety description cannot establish comparative safety. The registry record does not report the detail needed to assess the primary result's precision, the analysis of multiple outcomes, or the handling of missing observations.

The conclusions that can be drawn are therefore narrow: the study's design, regimen, endpoint schedule, and selected safety counts are recorded, while the primary numerical pharmacokinetic result and many safety details are not reported in the registry record. Any broader claim about effectiveness, comparative safety, or application beyond the study conditions would go beyond what this record documents.

14. Why This Trial Matters Statistically

This study illustrates how a trial can focus on pharmacokinetic characterization rather than a randomized estimate of clinical treatment effect. The endpoint is a measurable plasma concentration, and the sampling schedule defines the opportunities to observe a peak. Interpretation requires attention to both the summary statistic and how measurements were collected. A mean without its dispersion or uncertainty would give an incomplete account of the data; in this record, the numerical mean and standard deviation are not reported.

The single-group design also makes the distinction between description and comparison especially important. Observations in the treated group can characterize what was recorded under the study regimen, but without a concurrent comparator they do not estimate a treatment contrast. This distinction applies to the safety counts as well as to pharmacokinetic findings.

The record offers another useful statistical lesson: listed endpoints are not the same as reported results. Multiple safety categories and clinical measurements are named, but detailed outcomes and analysis methods are not available in the registry record. Without that information, readers cannot assess multiplicity handling, missing-data assumptions, or the precision of most estimates.

Finally, planning illustrations should be kept separate from the trial's actual design and results. The recorded planning assumptions describe a hypothetical two-arm framework, while this study is identified as single-group. Planning calculations can help frame future studies, but they are not observed evidence and do not replace a protocol's sample-size rationale. Recognizing these distinctions helps prevent overinterpretation of descriptive pharmacokinetic and safety records.

15. 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 central limitation for interpreting this trial record is the absence of the primary Cmax numerical result. Although the endpoint, unit, summary parameter, variability measure, and sampling schedule are defined, the mean and standard deviation are not reported in the registry record. No interval estimate or participant-level concentration data are reported either, so neither the observed level nor its precision can be assessed.

The single-group, open-label design provides no randomized comparator. It therefore cannot support a comparative estimate of pharmacokinetic or safety outcomes. The study's population is limited to pediatric subjects with atopic dermatitis under the recorded maximal-use regimen; the registry record does not establish how observations would apply under other conditions.

Safety reporting is also incomplete in the recorded information. The record gives counts for serious events, deaths, and other adverse events, but specific event terms, timing, severity details, and detailed results for the listed safety measures are not reported in the registry record. The number and criteria of participants in the pharmacokinetic analysis population are not reported in the registry record.

Further limitations include the absence of recorded information about missing observations, analysis methods, multiplicity procedures, and the protocol's sample-size justification. The registry lists 14 outcomes and 0 analyses, but those entries do not establish which analyses were performed or how they were conducted. These limitations restrict interpretation of the record; they do not establish that the unreported analyses or information do not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetics and Safety of MM36 Topical Ointment in Pediatric Subjects With Atopic Dermatitis — NCT02945657.
• Registry record last updated 2018-11-19; status last verified 2018-11.
• Results first posted 2018-11-19.
• 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.

19. Record Summary

NCT02945657 is a completed Phase 2, multicenter, open-label, single-group study of MM36 topical ointment, 1%, in pediatric subjects with atopic dermatitis. The regimen was twice daily for 28 days. Enrollment was 32, and the study began in 2016-10 with primary completion on 2017-06-08.

The primary outcome was maximum observed plasma concentration of MM36 on Day 1, summarized as a mean with standard deviation, with sampling before dosing and at 1, 4, and 8 hours post-dose. Its numerical result is not reported in the registry record. The safety record lists 0 serious adverse events among 31 at risk, 0 deaths, and 7 affected in the other-adverse-event category among 31 at risk. Detailed safety results and the statistical analysis methods are not reported in the registry record.