Pharmacokinetic (PK) and Tolerance Study of Natroba Topical Suspension in Pediatrics With an Active Head Lice Infestation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic (PK) and Tolerance Study of Natroba Topical Suspension in Pediatrics With an Active Head Lice Infestation (NCT01660321), a na phase 4 study. The primary outcome is Cmax for Spinosyn A.

2. Clinical Question

This is a pharmacokinetic question, not a comparison of treatment outcomes between randomized groups. Cmax describes the highest measured plasma concentration for the analyte over the sampling period. In general, pharmacokinetic measurements can help characterize how much of a drug-related substance is measurable in blood and how concentrations change over time. They do not, by themselves, establish a clinical benefit or a comparative effect.

The registry record describes a study in young children with active infestation and a single treatment. Its primary endpoint concerns spinosyn A concentration, while the record also reports safety counts. It does not provide a summarized estimate of the primary endpoint. Consequently, the central question is what the sampling and reported quantification limits allow readers to conclude about measurable plasma exposure—not whether Natroba performed better than another treatment.

3. Trial Design

This completed Phase 4 study was registered as a single-group pharmacokinetic and tolerance study. Its official title describes a single treatment of Natroba (spinosad) topical suspension, 0.9%, in pediatric subjects 6 months to 4 years of age with active head lice infestation. The registry lists 26 participants as the enrollment and identifies ParaPRO LLC as the sponsor.

The study started in 2011-09 and had a primary completion date of 2011-10. Its status is completed. The listed intervention is spinosad, and the arm description identifies Natroba topical suspension, 0.9%. Allocation is recorded as not applicable, masking as none, and the model as single group. There is therefore no randomized treatment comparison or masked control group described in the registry record.

Blood samples for the primary pharmacokinetic measure were collected before treatment and at 0.5, 1.0, 3.0, 6.0, and 12 hours after treatment. The primary endpoint is Cmax for spinosyn A, expressed in ng/mL. The endpoint population is described as Per Protocol. These design features define a short-term concentration assessment in a specific pediatric population; they do not describe a comparative efficacy trial.

The registry record does not report the rationale for the enrollment target, details of the recruitment process, participant characteristics beyond the stated age range and infestation, or a fuller account of the protocol. A statistical analysis plan, sample-size justification, interim analysis plan, and information about any changes to the planned design are not reported in the registry record. Planning illustrations associated with the posted results should be distinguished from the trial’s actual design: they are not evidence that the trial enrolled participants according to a comparative power calculation.

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

Analysis population for the primary outcome, as defined in the registry: Per Protocol. For all but 1 subject (Subject 02-202), all spinosyn A and spinosyn D concentrations were Below Quantification Level (BQL) or \< 3.0 ng/mL for all samples. Therefore, Cmax, Tmax, and AUC 0-12 were not summarized.

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 Cmax for Spinosyn A, measured over Blood samples collected up to 12 hours post treatment - 0 (pre-treatment), 0.5, 1.0, 3.0, 6.0 and 12 hours post-treatment..

The primary endpoint is Cmax for spinosyn A, measured in ng/mL. Cmax is the peak plasma concentration observed for a substance across the scheduled blood-sampling times. In general, it is used in pharmacokinetic work to describe the highest measured systemic concentration during a specified observation period. It is not a direct measure of clinical response, and it does not by itself describe the full concentration-time profile.

Blood samples were collected before treatment and at 0.5, 1.0, 3.0, 6.0, and 12 hours after treatment. The registry describes the endpoint population as Per Protocol. The primary endpoint description also states that, for all but 1 subject (Subject 02-202), all spinosyn A and spinosyn D concentrations were Below Quantification Level (BQL) or < 3.0 ng/mL for all samples. As a result, Cmax, Tmax, and AUC 0-12 were not summarized.

In general, a quantification limit means that the assay cannot report a reliable numerical concentration below a specified threshold. Such a result is not equivalent to a measured concentration of zero. When most observations are below the threshold, a conventional summary of peak concentration may not be informative or may not be available. The registry record does not report a summarized Cmax estimate, its variability, or a confidence interval. It also does not report the procedure used to handle below-quantification results in a numerical analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary measure is Cmax for spinosyn A, with concentration expressed in ng/mL. The endpoint is described for the Per Protocol population. Blood samples were collected before treatment and at 0.5, 1.0, 3.0, 6.0, and 12 hours after treatment. The primary endpoint description states that the concentration summaries were not produced because almost all reported spinosyn A and spinosyn D concentrations were below the quantification level or < 3.0 ng/mL.

What does Cmax describe?

In general, Cmax is the largest measured concentration in a set of samples collected over a stated period. It describes a peak among observed measurements, not necessarily the exact biological peak between sampling times. Its interpretation depends on the collection schedule, assay performance, and the rule used to select or estimate the peak. The registry record identifies the endpoint and collection times but does not report a fuller derivation method or a numerical Cmax summary.

Tmax is the time associated with the observed peak, while AUC describes concentration accumulated over a time interval. These are general pharmacokinetic concepts. The registry record names Tmax and AUC 0-12 as measures that were not summarized, but does not provide estimates for either measure. Their mention does not establish that a particular result was obtained.

How should below-quantification observations be read?

In general, an assay’s lower quantification limit marks a level below which it cannot reliably report a numerical concentration. A below-quantification result is not automatically zero, and it does not identify the actual concentration. It is a threshold-based observation. When many samples fall below the limit, ordinary summaries based on numerical concentrations may be difficult to calculate or interpret. The record reports that all but 1 subject had all spinosyn A and spinosyn D concentrations BQL or < 3.0 ng/mL across all samples. It does not report a statistical method for assigning values to those observations, nor does it give the measurements for Subject 02-202.

Analysts may use different approaches for data below a quantification limit, depending on the assay and the prespecified plan. General possibilities include reporting the frequency of values below the threshold, using methods that account for censored observations, or presenting individual concentration profiles when appropriate. These are methodological examples, not methods confirmed for this study. The analysis approach is not reported in the registry record. Because the endpoint summary itself was not produced, a reader should not infer that any particular substitution, model, or handling rule was used.

What can an estimate and confidence interval contribute?

In general, an estimate gives a numerical summary of a parameter, while a confidence interval describes uncertainty around that estimate under the assumptions of the analysis. A narrow interval usually indicates greater precision than a wide interval, but interval interpretation also depends on study design and the validity of the model. This record gives no Cmax estimate or confidence interval. It therefore does not allow readers to assess the precision of a population-level peak concentration estimate. No p-value or formal hypothesis test for the primary pharmacokinetic endpoint is reported.

The study is registered as single group, with allocation not applicable and no masking. There is no comparator group described for the primary endpoint. Consequently, a between-group treatment contrast is not available from this design. In general, a single-group pharmacokinetic study can describe measurements collected after treatment, but without a comparator it cannot estimate a randomized difference between treatment strategies.

How do planning calculations differ from trial results?

In general, power and sample-size calculations describe what a future or planned study might require under chosen assumptions. They are not observed outcomes and do not determine whether a result was statistically significant. The planning assumptions associated with this record specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of an observed effect. Those assumptions describe a planning illustration, not this single-group study’s design. The record does not report the trial’s own sample-size justification, and a planning calculation should not be treated as observed power.

Any calculated participant targets per arm for a power scenario are planning quantities, not counts of participants who experienced an outcome. In general, such calculations depend on the assumed effect, variability, test, allocation, and significance level. The registry record does not report a protocol-based justification linking the enrollment of 26 to a particular power target. The primary outcome’s lack of a summarized Cmax estimate also limits what can be inferred from calculations framed around an observed effect. A planning illustration cannot substitute for an endpoint estimate or a formal analysis of the collected data.

The record lists 9 outcome measures and 0 analyses. These counts do not reveal whether additional analyses were conducted but not posted; the statistical analysis plan and any analysis not included in the registry record are not reported there. The available endpoint description gives the reason the primary pharmacokinetic summaries were not produced. It does not specify inferential procedures, covariate adjustment, or sensitivity analyses.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 9 outcome measures and 0 analyses. It identifies Cmax for spinosyn A as the primary outcome and states that Cmax, Tmax, and AUC 0-12 were not summarized because nearly all reported concentrations were below the quantification level or < 3.0 ng/mL. The record does not provide a set of inferential results across outcomes, so it does not permit an assessment of how multiple statistical tests were handled.

Multiplicity refers, in general, to the increased chance of obtaining a seemingly unusual result when many hypotheses or outcomes are tested. Studies may prespecify a hierarchy, adjustment, or other strategy to address multiple testing. The multiplicity strategy is not reported in the registry record. The listed outcome count alone does not establish which outcomes were analyzed, whether they were tested, or whether any adjustment was applied.

The primary endpoint is described for the Per Protocol population. The record does not describe other analysis populations or state how participants were included or excluded from each outcome analysis. It does not report missing-data counts, reasons for missing samples, imputation methods, or sensitivity analyses. The description of below-quantification concentrations is not the same as a report of missing data: those samples are characterized by their relation to an assay threshold, while the handling of any uncollected or unavailable samples is not reported.

The registry record also does not report an interim analysis plan, stopping rules, or a complete statistical analysis plan. These omissions mean readers cannot establish whether the posted results reflect all planned analyses or how analytic decisions were specified before data review. No additional details should be inferred from the absence of analysis entries.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent non-serious adverse event terms

The Natroba group lists 26 participants at risk for serious adverse events and 0 participants affected. For other adverse events, 26 participants were at risk and 9 were affected. These are counts from the registry record, not rates calculated. The record does not list serious adverse event terms among its top serious terms. The death count is not reported in the registry record.

In general, an at-risk count is the number of participants represented in the relevant safety group, and an affected count is the number recorded as having the event type. These counts do not describe event severity beyond the category used, the timing of events, or whether an event was considered related to treatment. The registry record does not provide those details in the listed summary.

A recorded count of 0 serious adverse events in this group means that none are listed as affected in this safety summary. It is not proof that serious events are impossible, and it should not be interpreted as a complete characterization of risk. The group size and study design limit what these counts alone can establish. The other adverse event count is separate from the primary pharmacokinetic endpoint, which was not summarized.

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

The registry record describes a completed, single-group study of a single treatment of Natroba topical suspension, 0.9%, in pediatric subjects 6 months to 4 years of age with active head lice infestation. Its primary question concerns spinosyn A peak plasma concentration. The posted endpoint description says that Cmax, Tmax, and AUC 0-12 were not summarized because, for all but 1 subject (Subject 02-202), all spinosyn A and spinosyn D concentrations were BQL or < 3.0 ng/mL at all sampled times.

This means the posted results do not offer a numerical Cmax estimate or a measure of its precision. It is appropriate to describe the recorded quantification pattern, but not to replace unquantified observations with zero or to infer a population concentration from the record. The result does not establish the exact concentration for samples below the assay threshold, and the record does not give the values for Subject 02-202.

The study has no comparator group and is not recorded as randomized or masked. It therefore does not provide a randomized comparison with another treatment. The data described in the record do not establish a comparative clinical effect, and the concentration findings should not be converted into a claim about clinical benefit or lack of benefit. The primary endpoint is a pharmacokinetic measure, not a direct clinical outcome.

The safety summary records 0 participants with serious adverse events and 9 with other adverse events among 26 at risk in the Natroba group. These counts do not show event timing, attribution, or a comparative safety contrast. The death count is not reported in the registry record. The study’s enrollment, limited age range, single-group design, and endpoint reporting constrain the conclusions that can be drawn from the posted information.

In general, a study can be informative about whether an assay quantified concentrations at specified sampling times even when it cannot provide a conventional summary estimate. That is the relevant statistical distinction in this record. The available information supports a narrow reading of the observed quantification pattern and safety counts, not a broader conclusion about outcomes beyond those data.

13. Why This Trial Matters Statistically

This study illustrates a practical issue in pharmacokinetic analysis: the primary measure may be difficult to summarize when most samples fall below the assay’s quantification threshold. A below-quantification observation is not a numerical concentration and is not equivalent to zero. When such observations dominate the sampling record, the usual peak, variability, and time-course summaries may not be available or may require methods that are described in advance and reported transparently.

The record identifies Cmax for spinosyn A as the primary endpoint and gives the blood collection schedule through 12 hours after treatment. It also explicitly states why Cmax, Tmax, and AUC 0-12 were not summarized. That explanation helps distinguish an unavailable endpoint summary from a numerical estimate that happened to be small. No summarized Cmax value or interval is reported, so statistical precision cannot be judged from the posted endpoint information.

The design also clarifies the difference between pharmacokinetic description and comparative inference. A single-group study can collect concentration measurements after treatment, but it does not contain a randomized comparator for estimating a treatment contrast. The absence of a comparator is particularly important when readers are tempted to interpret a concentration endpoint as evidence about clinical outcomes. The registry record does not provide that kind of comparative result.

Finally, the study shows why planning calculations should be kept separate from actual evidence. Planning illustrations depend on assumptions and are not observed power, a result, or the trial’s own sample-size justification. The record’s single-group design differs from the equal-allocation, two-arm assumptions stated for the planning illustration. Keeping these distinctions clear prevents planning quantities from being mistaken for trial findings.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpreting the primary endpoint is that no Cmax, Tmax, or AUC 0-12 summary is reported. The registry attributes this to all but 1 subject (Subject 02-202) having all spinosyn A and spinosyn D concentrations BQL or < 3.0 ng/mL at all samples. The actual values for the exception, individual profiles, and any group-level concentration estimates are not reported in the registry record. The exact handling of below-quantification results is also not reported.

The design is single group, with allocation not applicable and masking none. No comparator is available to support a treatment contrast, and the endpoint does not by itself measure a clinical outcome. Enrollment was 26, and the population is restricted to pediatric subjects from 6 months to 4 years of age with active head lice infestation. The record does not give further participant characteristics that would allow readers to assess how closely the enrolled group represents other populations.

Sampling for the primary endpoint is described through 12 hours after treatment. The registry does not report concentration results beyond that interval, and longer-term pharmacokinetic information is not reported in the registry record. The entry also does not report the assay’s fuller validation characteristics, the planned statistical analysis methods, a sample-size justification, or handling of missing samples. These details should not be inferred from the posted endpoint description.

The safety summary gives affected counts but does not provide event timing, attribution, or the death count. The statistical analysis plan, interim analysis plan, and multiplicity approach are not reported. These limits make the available information suitable for a restrained description of the registered design, quantification pattern, and recorded safety counts, rather than a broad assessment of comparative outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetic (PK) and Tolerance Study of Natroba Topical Suspension in Pediatrics With an Active Head Lice Infestation — NCT01660321.
• Registry record last updated 2012-11-22; status last verified 2012-11.
• Results first posted 2012-11-19.
• 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.

18. Record Summary

NCT01660321 is a completed Phase 4, single-group pharmacokinetic and tolerance study sponsored by ParaPRO LLC. The registry lists an enrollment of 26, a start date of 2011-09, and a primary completion date of 2011-10. The population was pediatric subjects 6 months to 4 years of age with active head lice infestation.

The intervention was a single treatment of Natroba (spinosad) topical suspension, 0.9%. The primary endpoint was Cmax for spinosyn A in ng/mL, based on blood samples collected before treatment and through 12 hours after treatment. The endpoint was not summarized because all but 1 subject had all spinosyn A and spinosyn D concentrations BQL or < 3.0 ng/mL at all samples.

The safety listing records 0 participants with serious adverse events and 9 with other adverse events among 26 at risk. The death count and fuller analysis methods are not reported in the registry record. There is no comparator group, and no summarized primary concentration estimate is posted.