Dermal Safety Study to Evaluate Potential Irritation of Abametapir Lotion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dermal Safety Study to Evaluate Potential Irritation of Abametapir Lotion (NCT02061813), a randomized phase 1 study. The primary outcome is Potential of Abametapir Lotion to Cause Irritation After Repeated Topical Application to the Healthy Skin of Humans..

2. Clinical Question

The study was designed to assess cumulative irritation on healthy skin, rather than to evaluate treatment of head lice. Although Head Lice is listed as a condition in the registry record, the stated study purpose and primary outcome concern potential skin irritation after repeated topical application. The outcome therefore describes the observed irritation scores under the study’s patch-test conditions. It does not by itself address use on affected skin or establish results for other settings.

3. Trial Design

The registry describes a completed Phase 1 study with randomized allocation, double masking, and a parallel design. Its official title identifies a 21-day controlled study using a cumulative irritant patch test design. The stated purpose was to determine the irritation potential of repeat applications of abametapir lotion on normal skin. The study start and primary completion are both recorded as 2014-01.

Four applications are named: abametapir lotion 0.74% w/w, vehicle lotion, sodium lauryl sulphate (SLS), and saline 0.9%. The arm descriptions state that each was applied topically in a 0.2 mL amount under occlusive conditions. SLS is identified as the positive control and saline as the negative control. Vehicle lotion is the comparator for the principal abametapir contrast.

The registry lists enrollment as 40, while each of the four posted outcome groups reports 40 participants. The record does not explain the relationship between the enrollment figure and the group counts, so they should be read as separate reported figures rather than reconciled by assumption. Randomization, masking, and a parallel model describe broad features of the trial, but details such as the randomization procedure, concealment, masking assessment, and allocation implementation are not reported in the registry record.

The primary outcome was assessed daily from baseline through the Day 21 visit, with a final result described as the mean of scores over 21 days. The primary population is listed as all randomized subjects. Further operational details, including the specific patch schedule, analysis methods, and handling of deviations from the intended application schedule, 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: All Randomized Subjects

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 Potential of Abametapir Lotion to Cause Irritation After Repeated Topical Application to the Healthy Skin of Humans., measured over 21 days.

The primary endpoint is the mean score for potential irritation after repeated topical application to healthy human skin. A trained evaluator visually assessed patch sites for irritation symptoms using the Modified Berger procedure. Scores use numerical equivalents from 0 to 7, where 0 represents the least irritation potential and 7 the maximum irritation potential. The stated assessment was performed daily from baseline through the Day 21 visit, and the final outcome is the mean of scores over 21 days.

A mean summarizes the level of scores across the assessment period in a single continuous measure. It can make the overall pattern easier to compare across application groups than considering each daily assessment separately. The registry identifies the reported summary as a mean with standard deviation. The standard deviation describes variability among scores within a group; it is not the same as uncertainty around the group mean.

The cumulative irritant patch test is described in the registry as an accepted standard methodology for assessing cumulative irritation potential. In this design, the repeated assessments are relevant because the question concerns irritation across repeated applications, not only a single application. The endpoint is specific to the scoring method, application conditions, healthy-skin population, and assessment period described in the record. Details such as evaluator agreement, score aggregation when assessments were missing, and any additional endpoint validation are not reported in the registry record.

7. Results Posted in the Registry

• Abametapir Lotion Group: mean 1.10 versus 0.70 on control; difference 0.40 (95% CI -0.92 to 1.72), standardized effect d = 0.13; z-test p = 0.551.
• Saline 0.9%: mean 1.10 versus 0.70 on control; difference 0.40 (95% CI -1.80 to 2.60), standardized effect d = 0.08; z-test p = 0.721.
• Sodium Lauryl Sulphate (SLS): mean 49.15 versus 0.70 on control; difference 48.45 (95% CI 45.56 to 51.34), standardized effect d = 7.34; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted outcomes are continuous means: each group’s result summarizes a numerical irritation score, and the main contrasts are differences between group means. A mean difference is expressed in the same units as the outcome. A positive value in the reported contrast means that the comparison group’s mean is higher than the vehicle mean, according to the ordering used in the posted results. For abametapir and saline, that difference is 0.4; for SLS, it is 48.45. The registry does not provide a separate detailed statistical-analysis plan.

What does a confidence interval describe?

A confidence interval conveys uncertainty around an estimated quantity. It gives a range of values compatible with the observed data under the method used to construct the interval. A wide interval indicates that the estimate is not sharply determined; an interval spanning zero for a mean difference includes no difference as one of its compatible values. This does not mean that every value in the interval is equally likely, nor does it give the probability that the true value lies within that particular interval. The interpretation depends on the statistical method and assumptions, which are not fully described in the registry record.

For the abametapir-versus-vehicle contrast, the 95% interval crosses zero, as does the saline-versus-vehicle interval. The interval for SLS versus vehicle is entirely above zero. These descriptions concern the estimated group mean differences, not individual participants’ scores. They also do not establish whether any difference is important in a practical or clinical sense; no threshold for a meaningful difference is reported in the registry record.

How should the standard deviation be read?

The standard deviation describes how dispersed observed values are around a group mean. A larger standard deviation means the scores were more variable within that group. It is not a measure of how uncertain the mean is, and it is not a confidence interval. The group standard deviations are 3.11 for abametapir, 2.89 for vehicle, 6.48 for saline, and 8.87 for SLS. The saline and SLS results show greater reported spread than the abametapir and vehicle results. The record does not explain the unusual relationship between the stated score range and the SLS mean, so the reported values should not be altered.

In a general comparison of means, uncertainty depends on both variability and the amount of information in each group. Repeated assessments on the same participant can also create dependence: scores from one participant may be more alike than scores from different participants. A method that treats repeated measurements as independent when they are correlated could misstate uncertainty. The registry describes daily scoring and a final mean over 21 days, but it does not report the model or variance method used for the posted comparisons. It is therefore not possible to determine from the registry record how within-participant dependence was handled.

What do p-values add?

A p-value summarizes how surprising data at least as extreme as those observed would be under a specified null hypothesis and analysis model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of a difference. The unadjusted p-values are 0.551 for abametapir versus vehicle, 0.721 for saline versus vehicle, and <0.001 for SLS versus vehicle. The first two values accompany confidence intervals that cross zero. The SLS comparison has a much larger posted difference and an interval above zero. These p-values are reported as unadjusted; the registry record does not describe any multiplicity correction.

The confidence intervals and p-values are related summaries when they use compatible methods, but the registry does not document the methods in enough detail to verify that relationship. The comparisons should consequently be interpreted as posted, without assuming a particular model, adjustment, or treatment of repeated measurements. No analyses are listed in the record’s analysis count, and a complete protocol-level statistical plan is not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion means observed variability exceeds what a statistical model assumes. If a model understates variability, standard errors may be too small and intervals too narrow; if it accounts for variability poorly in the other direction, precision may be understated. This concern is relevant in principle when scores are highly variable or repeated within participants. The posted summaries show different standard deviations across the four groups, but the registry does not report a model-based assessment of over-dispersion or a correction for it. It is not possible to conclude from these summaries alone whether over-dispersion was present or affected the comparisons.

The listed sample-size illustrations are separate from the original trial design. They use the observed contrasts and stated planning assumptions, so they describe hypothetical future planning under those assumptions. They do not establish the power of this completed study. Details of the original sample-size justification, interim analyses, missing-data methods, and any prespecified analysis hierarchy are not reported in the registry record.

10. Confidence Intervals and Precision

Precision is conveyed most directly by the confidence intervals for the mean differences. The abametapir-versus-vehicle estimate is 0.4, and its 95% confidence interval extends from -0.916 to 1.716. The interval includes zero and covers values on both sides, indicating that the data do not pin down the direction of the difference precisely. The saline-versus-vehicle estimate is also 0.4; its interval extends from -1.799 to 2.599 and likewise includes zero. These intervals are wide relative to their point estimates.

For SLS versus vehicle, the estimate is 48.45 and the 95% confidence interval runs from 45.56 to 51.34. Unlike the other two intervals, this one does not include zero. It indicates a more clearly separated mean contrast under the reported comparison. Its interpretation remains subject to the registry’s stated outcome description and the unexplained fact that the posted SLS mean is beyond the stated score range.

Precision should not be judged from the point estimate or p-value alone. The group standard deviations show different amounts of observed variability, and the registry does not provide confidence intervals for each group mean. The comparison intervals quantify uncertainty in mean differences, not the range of individual scores. The method used to account for repeated daily assessments is not reported in the registry record, which limits assessment of how well the intervals reflect the study design.

A confidence interval does not identify a clinically important threshold. The record does not report a threshold for a meaningful change in the irritation score, so statistical compatibility with a range of differences cannot be translated into a judgment about importance. The reported precision is also specific to this study’s healthy-volunteer population, patch-test procedure, and 21-day assessment period.

11. 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 for 80% power and participants per arm for 90% power; they are not total event counts. They are planning illustrations based on the observed effect, not the original trial’s design assumptions. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect.

For abametapir versus vehicle, planning for 100% of the observed effect gives 885 participants per arm for 80% power and 1,184 for 90% power. Planning for 75% of the observed effect gives 1,572 and 2,105 participants per arm, respectively; planning for 50% gives 3,537 and 4,735. For saline versus vehicle, the corresponding figures are 2,470 and 3,307 for 100% of the observed effect, 4,391 and 5,878 for 75%, and 9,879 and 13,225 for 50%. For SLS versus vehicle, the figures are 1 participant per arm for 80% power and 1 for 90% at 100% or 75% of the observed effect; at 50%, they are 2 per arm for both power levels.

The 80% and 90% columns describe the target probability of detecting the specified effect under the stated planning assumptions if that effect and model were appropriate. Higher target power generally requires more participants for the same effect. Smaller effects need more participants, which is reflected in the larger figures for the smaller fractions in the abametapir and saline comparisons. The unusually small SLS illustrations follow from its very large observed contrast and should not be transferred to the other comparisons. These figures are not observed power. The original sample-size justification is not reported in the registry record.

12. 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 = 0.400; pooled standard deviation σ = 3.002.
2. n = 2 × (1.96 + 0.842)² × 3.002² / 0.400² = 884.2, rounded up to 885 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 <- 0.4                      # observed difference in means
sigma <- 3.00201598929786                     # 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(2061813)
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 = 885 (80% power), 1,184 (90% power)
 75% of observed effect: n per arm = 1,572 (80% power), 2,105 (90% power)
 50% of observed effect: n per arm = 3,537 (80% power), 4,735 (90% power)
power.t.test: 885.1 
Simulated power at n = 885 per arm: 0.798 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no posted secondary outcome measures. It also lists no analysis entries. Three pairwise mean comparisons are reported: abametapir versus vehicle, saline versus vehicle, and SLS versus vehicle. Their p-values are explicitly unadjusted. The registry record does not report whether these contrasts were prespecified as a family, whether any adjustment for multiple comparisons was planned, or whether a particular comparison had priority beyond the stated primary outcome.

Multiplicity matters because testing several comparisons can increase the chance that at least one result appears statistically unusual under a set of null hypotheses. Adjustment methods can change the interpretation of p-values or intervals. Since no multiplicity procedure is described, the reported p-values should not be treated as multiplicity-adjusted evidence. The positive and negative control roles are stated, but their place in a formal testing hierarchy is not reported in the registry record.

The primary population is described as all randomized subjects. The posted groups each list 40 participants, while registry enrollment is 40; the record does not explain the relationship between those figures. The number and handling of missing daily scores, withdrawals, exclusions, or protocol deviations are not reported. It is also not stated whether the final mean required every daily score or how incomplete score series were handled.

Other analysis details are absent, including the statistical model, the method for calculating standard errors and confidence intervals, assumptions about distributions, and whether repeated assessments within a participant were modeled together. The record does not report an interim-analysis plan, a missing-data strategy, or sensitivity analyses. These omissions do not invalidate the posted summaries, but they limit independent assessment of how the comparisons were constructed and how robust they are to analysis choices.

14. 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.

The serious adverse event summary lists 40 subjects at risk, with 0 affected by a serious adverse event and 0 deaths. The separate other-adverse-event figures list 40 at risk and 0 affected. These are counts as reported for the group titled All Randomized Subjects.

A count of zero means that no affected participants are recorded in that category in this summary. It does not mean that the risk is known to be zero, and it does not establish that no event could occur in a larger or different population. The registry record does not provide event terms, severity details for non-serious events, the safety observation period, or a detailed account of how adverse events were collected. No serious adverse event terms are listed. The safety figures should therefore be read as the posted counts, not as a complete characterization of safety across all uses or populations.

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

The results describe mean irritation scores under a specific repeated-application patch-test procedure in healthy volunteers. Abametapir’s reported mean was 1.1, compared with 0.7 for vehicle, with a mean difference of 0.4. The confidence interval for this comparison crosses zero, and the unadjusted p-value is 0.551. The data therefore do not establish a clear difference between those group means. The interval also leaves uncertainty about the direction and size of the contrast.

The saline-versus-vehicle comparison has a mean difference of 0.4, an interval that crosses zero, and an unadjusted p-value of 0.721. The SLS comparison is markedly different in its posted summary: its mean was 49.15, and the difference from vehicle was 48.45 with p < 0.001. SLS is identified as the positive control. However, its reported mean exceeds the stated 0-to-7 scoring range, and the registry record does not explain this. The posted result should not be silently reconciled with the scale description.

These statistics do not establish how scores would behave in other populations, with different application conditions, or outside the 21-day assessment period. They do not address effectiveness for head lice, despite that condition being listed in the record. The study’s stated purpose is irritation assessment on normal skin, and the endpoint is a score produced by visual evaluation under a cumulative irritant patch-test design.

Statistical uncertainty is not the same as clinical importance. The registry does not report a threshold that would define an important score difference. Nor does it provide enough analysis detail to evaluate missing-score handling, repeated-measures methods, or multiplicity. The findings should be understood as the observed summaries and comparisons in this completed study, with those boundaries in mind, rather than as a broad conclusion about product performance or safety.

16. Why This Trial Matters Statistically

This study illustrates why design context matters when interpreting a continuous outcome. The endpoint is based on repeated daily visual assessments, but the final result condenses those observations into a mean over 21 days. That summary is convenient for comparing groups, yet it does not show the timing or pattern of scores across individual assessment days. The registry does not report separate daily results or the method used to account for correlations among repeated measurements.

The comparisons also illustrate the distinction between an estimate and its precision. The abametapir-versus-vehicle mean difference is modest in the context of its interval, which crosses zero and extends in both directions. The p-value alone does not resolve that uncertainty. The positive-control contrast is much larger in the posted results, while the negative-control contrast resembles the vehicle comparison in its point estimate. These groups provide context for reading the study, but the record does not describe a formal validation analysis or a prespecified testing hierarchy.

The record also highlights the importance of checking internal interpretability. It describes scores from 0 to 7 but posts an SLS mean of 49.15. Without an explanation, readers should preserve both reported details and avoid inventing a rescaling or correction. The registry enrollment and outcome-group counts also differ in presentation: enrollment is listed as 40, and each outcome group lists 40. The record does not explain their relationship.

Finally, planning figures based on the observed contrasts can be informative about how effect size influences sample-size requirements, but they are not evidence about the completed study’s power or the original design rationale. The original justification and detailed analysis plan are not reported in the registry record. These distinctions support a cautious reading of both the estimates and their limitations.

17. 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 leaves important design and analysis details unresolved. It identifies randomization, double masking, and a parallel model, but does not describe sequence generation, allocation concealment, masking procedures, or how adherence to masking was assessed. The registry lists an enrollment of 40, whereas each outcome group reports 40 participants; the relationship between these figures is not explained.

The outcome description says scores range from 0 to 7, while the posted SLS mean is 49.15. No explanation is reported, so the scale interpretation for that result is uncertain. The record also does not show daily score summaries, making it impossible to assess how irritation scores changed across the 21-day period or whether the final mean concealed different time patterns.

There is no reported detail on missing daily assessments, withdrawals, exclusions, protocol deviations, or the handling of incomplete score series. The statistical model, standard-error method, repeated-measures approach, and any adjustment for multiple comparisons are not reported. The comparisons are identified as unadjusted, and no secondary outcomes or analysis entries are listed.

The endpoint is tied to healthy skin and the specified patch-test conditions. The record does not establish that the results generalize beyond that setting. The original sample-size justification, interim analyses, and prespecified statistical plan are not reported in the registry record. Finally, the serious and other adverse-event summaries give zero affected participants but do not provide event terms or detailed collection and observation information.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Dermal Safety Study to Evaluate Potential Irritation of Abametapir Lotion — NCT02061813.
• Registry record last updated 2021-07-26; status last verified 2021-07.
• Results first posted 2021-07-26.
• 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.

21. Record Summary

NCT02061813 is a completed Phase 1 randomized, double-masked, parallel study of repeated topical abametapir lotion applications in healthy volunteers. The registry identifies a 21-day cumulative irritant patch test design and lists enrollment as 40. The primary endpoint is the mean irritation score across the assessment period, based on daily visual evaluation using the Modified Berger procedure.

The posted mean was 1.1 for abametapir and 0.7 for vehicle, with a difference of 0.4 and an unadjusted p-value of 0.551. Saline had the same reported mean as abametapir; SLS had a much higher posted mean and is identified as the positive control. The SLS mean is inconsistent with the stated score range, and the registry record does not explain why. Analysis details, missing-data methods, multiplicity handling, and the original sample-size justification are not reported in the registry record.