Phase 3 Trial to Assess the Safety and Efficacy of Natroba for the Treatment of Scabies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 3 Trial to Assess the Safety and Efficacy of Natroba for the Treatment of Scabies (NCT02485717), a randomized phase 3 study. The primary outcome is Number of Index Subjects Completely Cured of Scabies After a Single Treatment.

2. Clinical Question

3. Trial Design

The registry identifies NCT02485717 as a Phase 3, randomized, double-blind, placebo-controlled study of Natroba, the spinosad topical suspension, for scabies. Allocation was randomized, masking was listed as quadruple, and the study model was parallel. The sponsor was ParaPRO LLC. The record lists an enrollment of 291 and a completed status. The recorded start date was 2017-05-02, and the primary completion date was 2018-06-25.

The two treatment groups were Natroba (spinosad) and placebo. Each group’s treatment description specifies one topical application left on for 6 hours. The active suspension was listed as 0.9% spinosad; the placebo was described as having the same formulation without spinosad. The efficacy comparison reported 43 participants in each group. That analyzed count is smaller than the total enrollment, and the reason for the difference is not reported in the registry record. The primary population description says that participants analyzed had no missing observations for the outcome in their group.

The primary efficacy assessment was complete cure 28 days after treatment. The record also describes pharmacokinetic assessments of spinosad and benzyl alcohol following a single dose in a separate pediatric population aged 4-16 years. The listed secondary assessments include maximum concentration, time to maximum concentration, and area under the concentration-time curve over 0-12 hours for those substances. Numerical results for those secondary assessments are not reported in the registry record.

Randomization and masking describe design features intended to support a fair comparison and reduce the influence of expectations on care or assessment. The record does not describe the randomization procedure, how masking was maintained, or whether allocation concealment was used. It also does not report the detailed procedures for recruiting participants or assessing the primary outcome.

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: Exclusion Criteria #2 - Has a household member(s) who is not willing or not eligible to enroll. Exclusion Criteria #12 - Administration of systemic therapy for infectious disease within the prior 2 weeks.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants analyzed are based on the number of subjects who had no missing observations in each study group.

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 Number of Index Subjects Completely Cured of Scabies After a Single Treatment, measured over 28 days after treatment.

The primary endpoint counts index subjects completely cured of scabies 28 days after treatment. The registry’s definition is more specific than a report of symptom improvement: complete cure required that all signs and symptoms resolve, including burrows, inflammatory or non-inflammatory lesions, and pruritus. It also required microscopic or dermatoscopic evidence of cure, including absence of mites, eggs, and scybala, together with negative dermatoscopy for burrows.

This is a binary outcome at the participant level: each assessed participant either met the complete-cure definition or did not. Counting participants who meet a prespecified definition can make a clinical comparison easier to interpret than relying on an unspecified change in symptoms. The endpoint also combines clinical findings with microscopic or dermatoscopic assessment, so it represents the record’s defined clinical and diagnostic criteria rather than symptoms alone.

The time point matters because the endpoint concerns status 28 days after treatment, not immediate response or longer-term recurrence. The posted primary outcome gives counts of 30 participants in the Natroba group and 20 in the placebo group, with 43 analyzed in each group. The record says the analysis included participants with no missing observations in each group. It does not report how missing observations were handled beyond that population description, or whether any additional endpoint definitions were used in the analysis.

As with any endpoint, interpretation depends on how consistently the definition was applied and whether all relevant assessments were completed. Further detail on assessor training, adjudication, and the handling of uncertain findings is not reported in the registry record.

7. Results Posted in the Registry

• Natroba (Spinosad): 69.8% (30/43) versus 46.5% (20/43) on control; risk difference 23.3 percentage points (95% CI 3.0 to 43.5), risk ratio 1.50 (1.03–2.18); unadjusted two-proportion z-test p = 0.029.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary because the endpoint classifies each assessed participant as completely cured or not completely cured at the stated follow-up. For a binary outcome, a group proportion describes the fraction of assessed participants meeting the event definition. The posted counts are 30 of 43 for Natroba and 20 of 43 for placebo. The record’s definition of the analysis population is participants with no missing observations in each study group.

What does the risk difference express?

In general, a risk difference subtracts one group’s event proportion from the other group’s event proportion. It keeps the comparison on the absolute probability scale, which can help readers understand how far apart the observed group proportions are. The posted unadjusted risk difference is 0.233. Its confidence interval is reported as 0.030 to 0.435. The direction depends on the comparison order; the record identifies Natroba as the arm compared with placebo.

How do relative measures differ?

In general, a risk ratio divides one group’s event proportion by the other group’s event proportion. An odds ratio compares the odds of the event between groups, where odds are the number with the event relative to the number without it. Because these measures use different scales, their numerical values need not match. The posted risk ratio is 1.5, with a confidence interval from 1.03 to 2.185. The posted odds ratio is 2.654, with a confidence interval from 1.096 to 6.428. The registry does not describe whether these relative measures were adjusted for any baseline variables; the posted comparison is identified as unadjusted.

What does the p-value address?

In general, a p-value evaluates how unusual data at least as different as those observed would be under a specified null model and test assumptions. It is not the probability that the null model is true, and it does not convey the magnitude or clinical importance of a result. The posted unadjusted p-value is 0.029. The registry record does not report the full test specification, including whether any continuity correction or other small-sample procedure was used. It is therefore appropriate to identify the value as the posted unadjusted p-value rather than to infer unreported test details.

Why use a confidence interval?

In general, a confidence interval gives a range of values compatible with the observed data under the interval method’s assumptions. It communicates precision as well as direction: a narrow interval indicates a more concentrated estimate, while a wide interval indicates greater uncertainty about the effect size. A confidence interval is not a guarantee that the true effect lies within its endpoints. The interval method used for the posted risk difference is not reported in the registry record, so interpretation should not depend on assumptions about a particular construction method.

What does randomization contribute?

In general, random assignment aims to balance prognostic factors across groups on average and supports a causal comparison when the assigned groups are analyzed appropriately. Randomization does not ensure that every characteristic is identical between groups, especially in a relatively small analyzed sample. The record confirms randomized allocation but does not report the sequence-generation method, concealment details, or baseline characteristics for the efficacy population. The trial is also described as double-blind with quadruple masking listed in the record; operational details about who was masked and how masking was maintained are not reported.

What analysis-population details matter?

The registry states that primary participants analyzed were those with no missing observations in each group. This means the posted counts reflect the recorded complete-observation population, rather than necessarily every participant enrolled or randomized. In general, excluding participants with missing outcomes can affect a comparison if missingness relates to treatment assignment or outcome status. The registry does not provide enough information to assess that possibility or to determine whether other analysis populations were used. No adjusted analysis, protocol-defined handling of missing values, or sensitivity analysis is reported in the registry record. The interpretation should therefore stay with the counts and unadjusted estimates that are posted.

10. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an effect estimate. For the primary risk difference, the posted estimate is 0.233 and its confidence interval runs from 0.030 to 0.435. The interval gives a range of values compatible with the observed data under the method’s assumptions. It is not a range of outcomes for individual participants, and it does not mean that every value inside it is equally likely. The confidence level and construction method are not reported in the registry record.

The interval spans a substantial range of possible effect sizes, so the point estimate should not be treated as exact. The lower and upper limits are both on the positive side after rounding, but the distance between them shows that the magnitude remains uncertain. The reported risk ratio and odds ratio also have confidence intervals: 1.03 to 2.185 for the risk ratio, and 1.096 to 6.428 for the odds ratio. The interval for the odds ratio covers a particularly broad range of relative values, reinforcing that its precise magnitude is not pinned down by the posted data.

The efficacy comparison is based on 43 participants per group, although total enrollment was 291. Smaller analyzed groups generally yield less precise estimates than larger groups, all else equal. However, the registry record does not explain the difference between total enrollment and the primary analysis population, and the confidence interval alone cannot identify the cause. The record’s complete-observation definition and the absence of reported missing-data analyses are relevant when judging how well the precision estimate reflects all enrolled participants.

Precision is distinct from statistical significance and from clinical importance. A p-value does not replace a confidence interval, and an interval does not determine whether an effect matters in practice. The registry does not provide a threshold for a clinically important difference. The estimates describe the posted comparison, with uncertainty, rather than guaranteeing the same result in another population or study.

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 this binary-outcome comparison, not total events. They are illustrations based on the observed effect, not the trial’s original design calculation. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and detection of the stated fraction of the observed effect. The registry record does not report the trial’s own original sample-size assumptions or justification.

For planning at 100% of the observed effect, the illustration gives 70 participants per arm for 80% power and 93 participants per arm for 90% power. At 75% of the observed effect, it gives 127 participants per arm for 80% power and 169 participants per arm for 90% power. At 50% of the observed effect, it gives 289 participants per arm for 80% power and 386 participants per arm for 90% power.

In plain language, the 80% power column describes an assumed design that would have an 80% chance of detecting an effect of the stated size under the listed model and assumptions, if that effect were the true one. The 90% power column uses a higher target chance of detection under the same general planning framework. These are design-planning quantities, not probabilities that the reported trial result is correct. Smaller effects need more participants to detect under the stated assumptions, which is why the illustrated participant requirements increase as the assumed fraction of the observed effect decreases.

This is not observed power. The registry record does not report that these were the trial’s original targets, and the illustrations should not be interpreted as evidence about the trial’s actual design decisions. They are conditional planning examples based on the observed comparison.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.465; treatment proportion p₁ = 0.698; average p̄ = 0.581.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6977 = 1.3674.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6780 = 0.5706.
4. n = (1.3674 + 0.5706)² / (0.2326)² = 69.4, rounded up to 70 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
p0 <- 0.465116279069767                          # control proportion
p1 <- 0.697674418604651                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2485717)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 70 (80% power), 93 (90% power)
 75% of observed effect: n per arm = 127 (80% power), 169 (90% power)
 50% of observed effect: n per arm = 289 (80% power), 386 (90% power)
power.prop.test: 69.4 
Simulated power at n = 70 per arm: 0.802 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 efficacy outcome and six secondary pharmacokinetic assessments. The primary outcome concerns complete cure at 28 days. The secondary assessments concern benzyl alcohol and spinosad concentrations in pediatric subjects aged 4-16 years, including maximum concentration, time to maximum concentration, and area under the curve over 0-12 hours. Numerical results for those six secondary outcomes are not reported in the registry record.

When a study evaluates multiple outcomes, the chance of obtaining at least one apparently notable result can increase if each is tested separately without a plan for multiplicity. In general, prespecified priorities and an adjustment strategy can clarify how multiple tests should be interpreted. The registry does not report whether multiplicity was addressed, whether the secondary assessments were considered confirmatory or exploratory, or what testing hierarchy or adjustment method was planned. The posted primary p-value is unadjusted, so it should not be described as adjusted for the other outcomes.

The primary analysis population is described as subjects with no missing observations in each study group. This indicates that the posted efficacy counts reflect participants with available outcome observations, but the registry does not report how many primary observations were missing, why they were missing, or how missing outcomes were handled in any other analysis. It also does not report an intention-to-treat analysis or sensitivity analyses addressing missing data. In general, missingness may affect both the estimate and its uncertainty if the participants without outcome data differ systematically from those assessed.

The record provides 43 analyzed participants in each efficacy group, compared with total enrollment of 291, but it does not explain the flow from enrollment to the primary analysis. It is not possible from the registry record to determine how many were randomized, received treatment, completed follow-up, or were excluded from the endpoint analysis. Detailed analysis populations, protocol deviations, and reasons for exclusion are not reported. These gaps limit assessment of potential bias and of how broadly the primary result represents the enrolled population.

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 registry reports serious adverse events, other adverse events, and deaths separately for three recorded groups. In the Natroba group, 142 participants were listed at risk for serious adverse events and 142 for other adverse events; zero were affected in either category, and deaths were zero. In the placebo group, 129 were listed at risk in each adverse-event category; zero were affected in either category, and deaths were zero. In the pediatric PK Natroba group, 20 were listed at risk in each category; zero were affected in either category, and deaths were zero.

These figures mean that no participants in the recorded at-risk groups were reported as having the specified events in the posted adverse-event summary. They do not establish that no adverse experiences of any kind occurred, because the record presents serious and other adverse events as summary categories and does not provide event terms. No top serious-event terms are listed. The record does not describe the event collection period, the definitions used for each category, or how the safety groups relate to the efficacy analysis population.

The safety denominators differ from the efficacy counts of 43 per group. The record does not explain the relationship between the safety populations, total enrollment, and primary analysis population. Zero reported events should therefore be read as a description of the posted safety figures, not as proof of absence of risk or as a comparison of rates adjusted for exposure or follow-up.

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

The posted data describe a randomized comparison of Natroba and placebo for complete cure of scabies at 28 days. Among participants included in the primary analysis, the registry reports 30 cures among 43 in the Natroba group and 20 among 43 in the placebo group. The reported unadjusted risk difference is 0.233, with a confidence interval from 0.030 to 0.435 and an unadjusted p-value of 0.029. Those figures characterize the observed result and its statistical uncertainty.

They do not establish the exact effect that would occur in a new group of participants. The confidence interval indicates uncertainty in the size of the comparison, and the trial’s analyzed groups are limited in size relative to the total enrollment. The primary analysis is described as using participants without missing observations, while the registry does not explain the difference between the analyzed count and total enrollment. Missing-data and sensitivity analyses are not reported.

The data also do not answer every question about the study. The registry does not provide numerical results for the six secondary pharmacokinetic outcomes, a detailed statistical analysis plan, or a multiplicity strategy. The posted safety summary lists zero serious adverse events, zero other adverse events, and zero deaths in each of its recorded groups, but it does not report event terms or the detailed safety ascertainment procedures. These summaries should not be used to infer that there were no possible harms.

In general, statistical evidence from a trial informs a group-level comparison under the study’s design and analysis assumptions. It cannot determine an individual participant’s outcome, and a p-value is not a measure of clinical importance. The registry does not identify a threshold for a clinically important difference. The appropriate reading is therefore bounded: the posted complete-cure counts and unadjusted comparison favor a higher observed cure proportion in the Natroba group, while the size, generalizability, and broader benefit-harm interpretation remain limited by the information reported.

16. Why This Trial Matters Statistically

This trial is statistically notable because it reports a binary clinical endpoint with a clear event definition: complete cure required resolution of specified signs and symptoms alongside microscopic or dermatoscopic criteria. Such a definition makes the outcome more interpretable than an unspecified improvement measure, while also making consistent assessment important. The endpoint was evaluated 28 days after a single treatment, so the comparison addresses that recorded follow-up point rather than long-term outcomes.

The primary comparison gives both group counts and an unadjusted effect estimate with a confidence interval. Readers can therefore consider not only the direction of the observed contrast but also its uncertainty. The risk difference, risk ratio, and odds ratio express the comparison on different scales; reading them together can illustrate how effect measures depend on scale without treating them as interchangeable. The confidence intervals make clear that an estimate is not a precise forecast of the result in every future study.

The contrast between total enrollment of 291 and the 43 analyzed participants in each efficacy group is important for statistical appraisal. The record describes a complete-observation analysis population but does not explain the participant flow or missing outcomes. That limits evaluation of precision, possible selection effects, and how representative the primary result is of the enrolled population.

The record also lists pediatric pharmacokinetic objectives separately from the clinical efficacy outcome. This distinction matters: the efficacy counts cannot stand in for the unreported concentration measurements, and the secondary assessments do not have posted numerical results in the record. Finally, the planning illustrations show how assumptions about effect size and power translate into different participant requirements, but they are not the original design justification. The original sample-size assumptions and multiplicity plan are not reported.

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 primary efficacy comparison is based on 43 participants in each group, while total enrollment is 291. The registry does not provide participant-flow details that explain this difference. It describes the primary analysis population as participants with no missing observations in each group, but does not report the number or reasons for missing observations, exclusions, or a sensitivity analysis. The possible effect of restricting analysis to complete observations therefore cannot be assessed from the record.

The registry reports an unadjusted comparison but does not give a detailed statistical analysis plan, the specific test used for the p-value, the method used to construct the confidence interval, or any adjusted analysis. Baseline characteristics for the analyzed efficacy groups are not reported in the information available. The randomization sequence, allocation concealment, and practical masking procedures are also not described, despite randomized allocation and the listed double-blind and quadruple-masking features.

The registry identifies one primary outcome and six secondary pharmacokinetic assessments, but does not report numerical results for the secondary outcomes or whether multiplicity was addressed. The record does not explain the relation between the pediatric PK group and the safety groups, nor does it provide detailed adverse-event terms or ascertainment periods. Zero events in the posted summary do not remove these reporting limits.

The primary endpoint is a composite definition requiring both clinical and diagnostic findings. The registry gives the criteria, but does not report assessor training, adjudication procedures, or the handling of ambiguous assessments. The follow-up point is 28 days after treatment; longer-term status and recurrence are not represented by this endpoint. These limitations constrain what can be concluded from the posted registry record and should not be filled in by assumption.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Phase 3 Trial to Assess the Safety and Efficacy of Natroba for the Treatment of Scabies — NCT02485717.
• Registry record last updated 2021-05-19; status last verified 2021-04.
• Results first posted 2019-01-16.
• 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

NCT02485717 is a completed, randomized, parallel Phase 3 trial comparing one treatment with Natroba (spinosad topical suspension, 0.9%) against placebo for scabies. The registry lists double-blind design and quadruple masking. Total enrollment was 291. The primary outcome was complete cure 28 days after treatment, defined using clinical and microscopic or dermatoscopic criteria.

The posted primary analysis included 43 participants per group: 30 were reported completely cured in the Natroba group and 20 in the placebo group. The unadjusted risk difference was 0.233, with a confidence interval from 0.030 to 0.435 and an unadjusted p-value of 0.029. Six secondary pediatric pharmacokinetic assessments are listed, but their numerical results are not reported in the registry record. The registry’s safety summary reports zero serious adverse events, zero other adverse events, and zero deaths in each listed group.

The record does not explain the difference between enrollment and the primary analysis population, or report detailed missing-data, multiplicity, or original sample-size methods. Interpretation is therefore limited to the posted outcomes and analysis descriptions.