Pharmacokinetic Study of AG200-15 Transdermal Patch to Three Anatomical Sites in Healthy Females: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic Study of AG200-15 Transdermal Patch to Three Anatomical Sites in Healthy Females (NCT01422135), a randomized phase 1 study. The primary outcome is Steady-State Concentration (Css) (48-168) Profile for LNG.

2. Clinical Question

The central statistical question is about pharmacokinetics: whether the measured concentration profile differs according to where the patch is applied. This is not a comparison of the patch with no patch or with another drug. Each listed sequence includes the three anatomical locations, with the order varying between sequences. The study description says pharmacokinetic sampling was performed after exposure to each location.

The record identifies a primary pharmacokinetic population and a mean as the outcome measure, with standard deviation as the dispersion measure. It does not give participant-level data, site-specific means, variability estimates, or an effect estimate comparing locations. Therefore, the endpoint description establishes what the investigators intended to measure, but the posted information does not establish what the measured profiles were or how precisely any difference was estimated.

In general, a crossover study can use within-participant comparisons because participants receive multiple conditions. That design can help separate differences between application sites from differences between participants. However, the registry record does not report the statistical model, handling of period or sequence effects, or a formal comparison. The clinical question is consequently clear at the level of study design, while its answer is not available in the posted results.

3. Trial Design

This was a phase 1, randomized, unmasked, crossover study sponsored by Agile Therapeutics. The registry record lists 24 participants and describes the population as healthy. The study status is completed. It began in 2011-02, with primary completion in 2011-04. These dates describe the record; they do not supply any unreported outcome results.

The intervention was AG200-15, a transdermal patch. The sequence descriptions show application at the abdomen, buttock and upper torso excluding the breast, with the order differing among sequences. The outcome description says pharmacokinetic sampling was performed after exposure to each anatomical location. The brief summary characterizes the study as pharmacokinetics and safety over 3 weekly applications. The primary outcome timeframe is listed as 6 weeks. The registry record does not explain the relationship between these two duration descriptions in further detail.

Randomization in this setting concerns assignment to an application sequence, as reflected in the listed orders. The record does not give the number of participants assigned to each sequence or a sequence-specific participant flow. It also does not describe concealment of sequence assignment. Masking is listed as none, so the study is described as unmasked.

In general, a crossover design differs from a parallel-group design because participants are exposed to more than one condition over time. This can make each participant a reference for their own measurements, but it also makes timing and sequence relevant to analysis. For example, a statistical analysis may need to account for measurement period, sequence, and possible residual effects from an earlier exposure. Whether and how those features were handled is not reported in the registry record.

The posted record does not report a protocol-level sample-size justification, target effect, or statistical plan. The enrollment of 24 is a study characteristic, not evidence by itself that the study was designed to detect a particular difference with a specified precision. No formal primary-outcome analysis is listed in the record. The tables and plots should therefore be read alongside that limitation: the registry description gives design and measurement details, but the inferential methods and primary results are not reported.

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: Primary PK population

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety population

6. Primary Endpoint

The registry lists the primary outcome as Steady-State Concentration (Css) (48-168) Profile for LNG, measured over 6 weeks.

The primary endpoint is titled “Steady-State Concentration (Css) (48-168) Profile for LNG.” It is a pharmacokinetic measure, expressed in pg/mL, and the recorded summary type is a mean with standard deviation. The timeframe is listed as 6 weeks. The description says that pharmacokinetic sampling took place after exposure to each anatomical location.

The listed sampling times are immediately prior to dosing and at 3 hours, 6 hours, 12 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days), 120 hours (5 days), 144 hours (6 days), and 168 hours (7 days) after patch application. The endpoint title focuses on the 48-to-168-hour profile, while the description also includes earlier sampling times. The record does not explain how those earlier measurements contributed to the primary endpoint.

In general, pharmacokinetic concentration measurements describe the amount of a drug or related substance measured in the body over time. A profile can show how measured concentration varies across sampling times; a steady-state measure is intended to characterize exposure after repeated dosing has reached a relatively stable pattern. The specific operational definition of Css for this study is not reported in the registry record, so it is not possible to determine from the description alone how steady state was defined or summarized.

These measurements are used to characterize exposure rather than to directly measure a clinical outcome. The registry record does not report the mean concentrations, standard deviations, or site comparisons for this endpoint. As a result, the endpoint’s purpose and measurement schedule are described, but the observed profiles and their precision cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, the method used to analyze a clinical trial should match its design, outcome type, and scientific question. Here, the registry describes a randomized crossover study and a continuous pharmacokinetic outcome summarized by a mean and standard deviation. However, the specific statistical method used for the primary endpoint is not reported in the registry record. The explanation below describes relevant statistical concepts, not a claim that any particular method was used in this study.

What does a crossover design change?

In general, a crossover design measures participants under more than one condition, with treatment or condition order assigned by sequence. A comparison can then use the fact that measurements from the same participant are related. This within-participant structure can reduce the influence of stable differences between participants, compared with treating every measurement as if it came from an unrelated person.

That structure also requires care. Measurements from one participant are correlated, so analyses generally should not treat them as independent observations. The timing of the measurement and the order of exposures can also matter. Period effects are systematic differences associated with when a condition is received; sequence effects relate to the order assigned. Carryover refers, in general, to an effect of an earlier condition persisting into a later period. The registry record lists different application orders, but does not report whether period, sequence, or carryover were assessed or how they were handled.

What does the outcome summary describe?

The primary endpoint is a concentration profile, a continuous measure recorded in pg/mL. The registry lists the mean and standard deviation. In general, the mean summarizes the central level of measured values, while the standard deviation describes their spread around that mean. A standard deviation is not the same as a standard error or confidence interval: it describes variability among observations, whereas inferential uncertainty in an estimated mean or contrast depends on the analysis and the amount and structure of data.

The listed pharmacokinetic sampling schedule includes several measurements after application. Repeated measures over time are related within a participant. In general, an analysis of a profile may summarize individual time points, model the time course, or define a derived exposure measure. The registry record does not report which approach was used, how the values across times were combined, or the precise operational definition of the titled Css outcome. No concentration values or model estimates are reported in the registry results.

What can a comparison estimate?

In general, a contrast between anatomical sites could be expressed as a difference in a concentration summary or as a comparison of profiles. The choice affects interpretation: a single-time-point contrast answers a narrower question than a comparison of the full time course. An estimate should be accompanied by a measure of uncertainty, such as a confidence interval, if the aim is to communicate its precision. The registry record does not report a site contrast, confidence interval, or p-value, and the record’s skip note indicates fewer than two arms in the primary outcome.

Randomization helps protect comparisons against systematic assignment differences, but it does not itself specify the analysis. For a crossover study, an appropriate analysis needs to respect the repeated observations and assigned sequences. Whether any adjustment or model was used is not reported in the registry record. The record also does not state assumptions about distributions, missing measurements, or the handling of values below or above assay limits.

How should dispersion and over-dispersion be understood?

In general, over-dispersion refers to variability greater than a statistical model expects. It is especially discussed for count outcomes, where a simple model may underestimate variability and consequently overstate precision. The primary endpoint is continuous concentration, not a count outcome. The registry record does not report an over-dispersion assessment, a distributional model, or any adjustment for unusually high variability. Readers should not infer that such a method was used from the outcome description alone.

What do planning illustrations mean?

The study information describes sample-size assumptions for a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. Such a calculation is a planning illustration, not the trial’s original design justification and not observed power. In general, observed power is not a substitute for reporting the estimated effect and its uncertainty. The numerical results of the illustration are not reported in the registry record, and no primary effect estimate is available from which readers could independently judge its inputs.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, but does not report a multiplicity strategy. Multiplicity arises when several outcomes, time points, comparisons, or statistical tests are examined. In general, if many tests are interpreted together without an appropriate plan, the chance of finding at least one apparently unusual result can increase. Methods such as prespecifying a primary comparison or adjusting inference may be used, but the registry record does not say whether either approach was applied.

The primary endpoint description includes multiple pharmacokinetic sampling times. The record does not explain whether each time point was analyzed separately, whether a profile-level summary was used, or how any repeated testing across times was handled. It also lists four outcome measures and zero analyses. No analysis plan, hierarchy of outcomes, or multiplicity adjustment is reported in the registry record.

Missing-data handling is not described. In general, missing concentration measurements can affect a repeated-measures analysis, particularly if the reason data are missing is related to participant characteristics or measured values. The record does not report the number of missing values, exclusions from the primary pharmacokinetic population, imputation, or sensitivity analyses. The primary population is named, but its size and inclusion criteria are not reported.

The safety groups have different numbers at risk, but the registry record does not explain the reasons for those differences. It would not be appropriate to infer that all enrolled participants contributed to every outcome or to assume a particular missing-data mechanism. The posted record supplies no participant flow or analysis-population detail to resolve this.

These reporting gaps limit how fully the results can be evaluated. They do not demonstrate that the investigators failed to conduct additional analyses; they mean that those methods are not reported in the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry safety entries separate serious adverse events, other adverse events, and deaths for each application-site group. For AG200-15 on the lower abdomen, 22 participants were at risk for serious adverse events and 0 were affected; 22 were at risk for other adverse events and 19 were affected. For the buttock, 23 were at risk for serious adverse events and 0 were affected; 23 were at risk for other adverse events and 23 were affected. For the upper torso excluding the breast, 23 were at risk for serious adverse events and 0 were affected; 23 were at risk for other adverse events and 21 were affected. The death count is 0 in each group.

These are reported counts, not a statistical comparison between sites. The numbers at risk differ, and the record does not give a reason for that difference. It also does not report event descriptions for the other adverse events or provide a statistical analysis of those counts. The registry lists no top serious-event terms.

In general, a zero count in a study group means that no event in that category was recorded for the listed participants; it does not by itself establish that the underlying risk is zero. Counts also do not show timing, severity beyond the serious/non-serious distinction, or whether a participant experienced more than one event. Those details are not reported in the registry record. The safety entries should therefore be read as descriptive information for this study, not as evidence of a comparative safety effect.

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

The study is relevant as a randomized crossover assessment of pharmacokinetics after applying the AG200-15 patch at three anatomical locations in healthy female volunteers. The registry describes the application sequences and the sampling schedule, and it identifies the steady-state concentration profile for LNG as the primary outcome. Those details help define the question the investigators set out to examine.

What the posted results do not provide is the answer in numerical terms. The record does not report the concentration measurements, site-specific summaries, differences between sites, confidence intervals, or p-values. It therefore does not show whether profiles were alike or different, nor how precisely any estimated contrast was measured. The design and endpoint description should not be mistaken for a finding.

The adverse-event entries offer limited descriptive information: each site group has a reported serious adverse event count of 0, and other adverse-event counts are also listed. The record does not provide a comparative safety analysis or enough detail to interpret the nature and timing of those other events. These data cannot, on their own, establish a difference or lack of difference between sites.

In general, a non-significant result, if reported, would not automatically demonstrate equivalence; an equivalence conclusion requires a defined margin and an analysis designed to evaluate it. Here, no primary comparison or equivalence framework is reported in the registry record, so neither conclusion can be drawn from the posted information.

The study’s stated enrollment of 24 and its phase 1 designation describe the study, but do not resolve the missing result information. The record does not report a sample-size justification or statistical plan. Any interpretation should remain limited to what is documented: a planned assessment of concentration profiles and registry-reported safety counts, without a reported primary statistical result.

13. Why This Trial Matters Statistically

This trial illustrates a common statistical distinction between a well-described measurement plan and a reported result. The record gives the outcome title, unit, summary type, timeframe, and sampling schedule. Those details tell readers what was to be measured, but they do not replace the estimates needed to judge the observed concentration profiles or their precision.

The crossover design also makes the analysis structure important. In general, within-participant comparisons can account for stable differences among participants, but repeated measurements are correlated, and exposure order and period can be relevant. The sequence descriptions make the order of application part of the study design. Yet the statistical model and its handling of sequence, period, and possible carryover are not reported in the registry record. This limits reproducibility and prevents readers from evaluating whether the analysis reflected the design.

The page also demonstrates why descriptive counts should not be treated as inferential results. The safety entries show counts at risk and counts affected, but no comparison or uncertainty estimate. A count can describe what was recorded in a group; it does not quantify how much groups differ or how uncertain that difference is.

Finally, a planning illustration based on an observed effect is conceptually different from the original design justification and from observed power. In general, planning calculations depend on assumptions about the target effect and analysis. If the outcome estimate and analysis are not reported, the assumptions behind such an illustration cannot be fully evaluated. The statistical lesson is to distinguish study design, measurement, descriptive reporting, and inferential evidence rather than treating them as interchangeable.

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 of the posted record is that it does not report the numerical results for the primary pharmacokinetic endpoint. No concentration means, standard deviations, contrasts, confidence intervals, or p-values are reported. Without those estimates, readers cannot assess the size or precision of any site-related difference.

The registry describes a primary pharmacokinetic population but does not report its size or define its membership. It lists an enrollment of 24, while safety-group denominators differ by site. Participant flow, exclusions, and reasons for differing numbers at risk are not reported. Missing concentration data and their handling are also not described.

The study is described as a randomized crossover, but its statistical model is not reported. The record does not state how repeated observations, application sequence, period effects, or possible carryover were addressed. It also does not report the exact operational definition of the Css profile or how measurements at the listed times were combined for analysis.

The brief summary says the study covered 3 weekly applications, while the primary outcome timeframe is listed as 6 weeks. The registry record does not further explain how those duration descriptions relate. The record also does not report the protocol-level sample-size rationale, a formal statistical analysis plan, or a multiplicity strategy.

Safety information is limited to group-level counts. Event descriptions for other adverse events and a comparative safety analysis are not reported. These limitations are specific to the details available in the registry record and should not be read as evidence about what may have been documented elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetic Study of AG200-15 Transdermal Patch to Three Anatomical Sites in Healthy Females — NCT01422135.
• Registry record last updated 2018-12-31; status last verified 2018-07.
• Results first posted 2018-12-31.
• 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

This completed phase 1 study was randomized, unmasked, and crossover in design. It lists an enrollment of 24 healthy female volunteers and evaluates AG200-15 patch application at the abdomen, buttock, and upper torso excluding the breast, using different application sequences.

The primary outcome is the steady-state concentration profile for LNG from 48 to 168 hours, measured in pg/mL and summarized by a mean and standard deviation. The description lists sampling from immediately before dosing through 168 hours after application, and a timeframe of 6 weeks. The brief summary describes 3 weekly applications.

The registry record does not report primary endpoint values or a statistical comparison between sites. It lists zero serious adverse events in each site group and reports other adverse-event counts, but no comparative safety analysis. The record lists four outcome measures and zero analyses.