Bioavailability and Safety Study Comparing Two Dose Levels of AMZ001 and One Dose Level of Diclofenac Sodium 1% Gel in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bioavailability and Safety Study Comparing Two Dose Levels of AMZ001 and One Dose Level of Diclofenac Sodium 1% Gel in Healthy Participants (NCT05968482), a randomized phase 1 study. The primary outcome is Compare Exposure to Diclofenac.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, open-label, single-center, three-period crossover study in healthy participants. The registry lists 74 participants enrolled and the study status as completed. Its stated purpose was to compare bioavailability after repeated topical administration of AMZ001 at two dose levels and diclofenac sodium 1% gel, while also investigating AMZ001 safety and tolerability.

In the crossover design, participants received three treatments: AMZ001 low dose, AMZ001 high dose, and diclofenac sodium 1% gel. Both AMZ001 regimens were applied once daily for 7 consecutive days; the reference gel was applied four-times daily for 7 consecutive days. The registry describes the reference treatment as the comparator and indicates that exposure was assessed on Day 7. The treatment sequence, period-specific procedures, and any washout interval are not reported in the registry record.

Randomization was used, but the registry does not report the allocation sequence or its implementation details. The study was open-label, meaning treatment assignment was not masked. The record does not explain whether outcome assessment or laboratory measurement was masked. It also does not report a planned sample-size justification, interim analyses, or a detailed statistical analysis plan.

The primary endpoint analysis included participants with at least one qualifying exposure measure for the reference treatment and at least one AMZ001 dose. The registry reports 69 participants for each of the three posted arm-level endpoint values. These arm-level counts do not by themselves describe the crossover sequence, the number of complete treatment-period sets, or the handling of participants with incomplete data. Those details 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.

First Crossover Period

Reasons for not completing this period:

Second Crossover Period

Reasons for not completing this period:

Third Crossover Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects for which at least AUC0-τ or Cmax can be determined for the reference treatment (Diclofenac Sodium 1% Gel) along with at least one of Treatments AMZ001 Low dose or AMZ001 High dose are included in the analysis 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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Compare Exposure to Diclofenac, measured over Day 7.

The primary endpoint was the area under the concentration-time curve from time zero to 24 hours on Day 7, reported in ng*hr/mL. AUC represents drug exposure over a specified period: it combines information about measured concentration and time rather than representing a single concentration measurement. In a repeated-dose topical study, the endpoint offers a way to compare the amount of diclofenac reaching the measured systemic compartment under the tested regimens. The registry identifies the endpoint as a pharmacokinetic measure, not a measure of symptom relief or another clinical outcome.

The registry reports geometric means and geometric coefficients of variation for the three treatment groups. A geometric mean is a summary suited to data that are positive and may be right-skewed; it is based on the logarithmic scale and then expressed on the original scale. The geometric coefficient of variation describes variability relative to the geometric mean. It is a measure of dispersion, not a confidence interval and not a measure of uncertainty about the estimated mean.

The posted values are 141.5 ng*hr/mL for AMZ001 low dose, 166.1 ng*hr/mL for AMZ001 high dose, and 202.3 ng*hr/mL for diclofenac sodium 1% gel. The corresponding geometric coefficients of variation are 89.8, 90.3, and 79.4. These summaries describe exposure in the analysed participants. The record does not report confidence intervals, a formal treatment contrast, or a statistical test for the primary endpoint, so the precision and inferential significance of differences between treatments cannot be assessed from these summaries alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary endpoint is a pharmacokinetic summary. It is the area under the concentration-time curve from time zero to 24 hours on Day 7, with units of ng*hr/mL. In general, AUC summarizes drug exposure over a defined time window. It differs from a single concentration such as a peak or trough: a concentration is measured at a particular time, whereas AUC reflects the accumulated concentration profile across the interval. Here, the record identifies AUC as the primary measure and also refers to Cmax in defining the analysis population.

What does a geometric mean describe?

In general, a geometric mean is calculated by transforming positive observations to the logarithmic scale, averaging there, and transforming the result back to the original scale. This can be useful for pharmacokinetic measures, which may have a skewed distribution and where multiplicative rather than additive variation is relevant. It is not interchangeable with an arithmetic mean. The registry reports geometric means of 141.5 ng*hr/mL for AMZ001 low dose, 166.1 ng*hr/mL for AMZ001 high dose, and 202.3 ng*hr/mL for diclofenac sodium 1% gel.

The geometric coefficient of variation is a relative measure of spread. In general, it describes how variable observations are in relation to their geometric mean, using a scale suited to log-transformed data. The reported values are 89.8, 90.3, and 79.4 for the low-dose AMZ001, high-dose AMZ001, and reference gel groups, respectively. These statistics do not give a confidence interval for the mean or a treatment contrast. They also do not reveal the distribution’s shape or the values for individual participants.

Why does the crossover design matter?

In general, a crossover study gives each participant more than one treatment, so treatment comparisons may use both between-participant and within-participant information. A participant’s stable characteristics can then be shared across treatment observations, potentially reducing variability in a comparison. Correct analysis must reflect the design, including the treatment and period structure; the treatment sequence can also matter. If treatment effects carry into a later period, that may complicate interpretation. The registry identifies a three-period crossover but does not report the treatment sequence, washout interval, or analysis model. Therefore, the posted arm-level summaries cannot establish whether the analysis accounted for these design features.

The study was randomized and open-label. In general, randomization helps balance measured and unmeasured baseline characteristics over treatment assignments, while masking can reduce some forms of expectation-related influence. Open-label means the treatments were not masked according to the registry. The record does not describe laboratory masking, allocation concealment, or the procedures used to implement randomization. Those details should not be inferred from the design labels alone.

What can be inferred from the posted summaries?

Descriptive summaries characterize observed data; inferential statistics quantify uncertainty about comparisons beyond the analysed sample. A confidence interval, in general, gives a range of values compatible with the data and the specified statistical procedure. A p-value, in general, measures how unusual the observed data would be under a stated null hypothesis and model. Neither can be reconstructed from geometric means and geometric coefficients of variation alone in a crossover study without additional information about paired observations and the analysis. The registry does not report a confidence interval, p-value, or formal treatment contrast for the primary endpoint.

The record lists 69 participants for each treatment’s primary endpoint summary. The enrolment count is 74, and the endpoint population required qualifying data for the reference treatment and at least one AMZ001 treatment. In general, such differences can arise from eligibility rules or unavailable measurements, but the specific reasons for the difference are not reported in the registry record. The identical reported treatment counts do not establish that every participant contributed data to all treatment periods or that all endpoint observations were complete.

Over-dispersion, in general, means that observed variability is greater than a statistical model assumes. When present, it can make standard errors too small if not addressed, resulting in overconfident inference. The geometric coefficients of variation indicate considerable relative variability, but they do not by themselves demonstrate model over-dispersion. The registry does not report a model, diagnostics, transformation details, or an approach to handling unusual values, so no conclusion about model fit can be made.

The record reports no posted analysis count for the primary comparison and describes the result as a single endpoint summary by treatment. It does not identify the model, adjustment factors, hypothesis-testing procedure, or whether any analyses were prespecified. Those statistical-plan details are not reported in the registry record. The result is therefore best interpreted as a set of descriptive exposure summaries, not as a completed inferential comparison of the treatments.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and seven posted secondary outcomes. The secondary outcome names include pharmacokinetic parameters such as Cmin, Tmax, Ke, and Cavg, as well as local tolerability; Tmax and Cavg appear more than once in the list. The record does not report a multiplicity-adjustment procedure, a hierarchy of hypotheses, or which secondary outcomes were intended to be confirmatory. When multiple outcomes or comparisons are tested, the chance of at least one apparently unusual result can rise. In general, prespecified testing strategies can address that issue, but the applicable strategy is not reported in the registry record. The posted primary endpoint summaries do not include inferential tests.

The registry defines the primary endpoint population as participants for whom at least AUC0-τ or Cmax could be determined for the reference treatment and for at least one AMZ001 dose. This definition allows a participant with data for one AMZ001 dose to meet the stated population criterion; it does not say that the participant must have complete data for all three treatments. The record reports 69 participants for each arm-level endpoint value, but does not describe missing data by treatment, period, or sequence, nor does it explain exclusions or imputation.

In general, missing-data methods matter because the reason data are unavailable may be related to treatment, outcome, or participant characteristics. Complete-case summaries describe those with available measurements, but their interpretation depends on how availability arose. The registry does not report whether missing values were imputed, whether sensitivity analyses were conducted, or how incomplete crossover sequences were handled.

The record also does not report a statistical analysis population beyond the endpoint eligibility description, or explain whether all randomized participants were included in any safety analyses. As a result, the completeness of the posted endpoint summaries and their relationship to the randomized population cannot be fully assessed from 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for each of the three treatment groups. For AMZ001 low dose, 71 participants were at risk and 0 had a serious adverse event. For AMZ001 high dose, 72 were at risk and 0 had a serious adverse event. For diclofenac sodium 1% gel, 72 were at risk and 0 had a serious adverse event. The record lists 0 deaths in each group.

These are observed counts in the safety groups described by the registry. They are not proof that serious events cannot occur or that the treatments have identical safety profiles. In general, a count of zero is interpreted in light of the number of participants observed, the duration and completeness of follow-up, and the event definitions. The registry information does not provide a comparative risk estimate or confidence interval for serious adverse events.

The record also lists other adverse events for 7 participants in the AMZ001 low-dose group, 8 in the AMZ001 high-dose group, and 5 in the reference-gel group. These counts are separate from the serious adverse event counts. The registry does not report event timing, severity details for the other events, attribution, or analyses that account for the crossover exposure and follow-up. The safety counts should therefore be read descriptively, not as a formal comparison between treatments.

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

The posted results describe Day 7 systemic diclofenac exposure after repeated topical use of two AMZ001 dose levels and diclofenac sodium 1% gel in healthy participants. The geometric mean AUC values are 141.5 ng*hr/mL for AMZ001 low dose, 166.1 ng*hr/mL for AMZ001 high dose, and 202.3 ng*hr/mL for the reference gel. The corresponding geometric coefficients of variation describe substantial variability around those treatment-specific summaries. This is a pharmacokinetic description of the participants with qualifying endpoint data.

The results do not, on their own, establish whether the treatments differ statistically. There are no posted confidence intervals, treatment ratios, or p-values for the primary endpoint. The geometric means can be compared descriptively, but their ordering is not a substitute for an analysis that accounts for the crossover design and quantifies uncertainty. The registry does not report enough detail to reconstruct such an analysis.

Nor do the reported values establish equivalence, noninferiority, or superiority. Those conclusions require a prespecified comparison, a clinically justified margin where relevant, and an appropriate inferential analysis. The registry record does not report such a margin or a corresponding test. The primary endpoint is exposure, not a clinical outcome, so it does not show whether participants experienced symptom improvement or another health benefit.

The safety figures show no serious adverse events or deaths reported in the listed groups, alongside other adverse event counts. These observations provide a descriptive account of events recorded in this study, but they do not rule out uncommon events or establish equal safety. The study was conducted in healthy participants, and the registry’s brief description focuses on bioavailability and safety after 7 days of repeated administration. Its findings should not be treated as evidence about treatment effects in patients or about longer-term use.

Interpretation is also limited by the absence of reported treatment sequence, washout information, missing-data handling, and a detailed statistical analysis plan. These details are important for understanding a crossover study and the precision of its comparisons. The available results support a narrow conclusion: the registry reports treatment-specific geometric mean exposure and variability for the defined analysis population, plus descriptive safety counts. Broader claims are not established by the posted record.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it uses a randomized crossover design to study drug exposure under three topical regimens. In general, crossover designs can support within-participant comparisons, which may be informative when the outcome varies substantially between people. The registry’s reported geometric coefficients of variation—89.8, 90.3, and 79.4—make it especially important to understand how the analysis handled the repeated treatment observations and the variability in exposure.

The primary endpoint is pharmacokinetic rather than clinical. AUC from time zero to 24 hours on Day 7 summarizes exposure over a defined interval after repeated administration. Distinguishing this kind of endpoint from a clinical outcome helps readers understand the scope of the evidence: exposure comparisons characterize drug disposition under the studied conditions, but do not by themselves demonstrate patient benefit.

The registry reports geometric means for all three treatments and endpoint counts of 69 for each. Those descriptive values are useful for seeing the reported scale of exposure and its variability. However, a crossover comparison relies on the relationship between measurements within the same participant, not only on separate treatment-specific summaries. Without a reported paired contrast, uncertainty estimate, or analysis model, readers cannot determine how precisely the treatments differed in the study.

The record also illustrates why clear reporting of analysis populations and missing data matters. The primary population definition requires a qualifying reference-treatment measure and at least one AMZ001 measure, while the study involved three treatments. The record does not specify how incomplete treatment sequences were handled. Transparent reporting of the analysis model, treatment sequence, missing-data approach, and any multiplicity strategy would make the statistical interpretation more complete.

Finally, the safety counts are worth distinguishing from comparative safety evidence. Zero serious adverse events were reported in each listed group, but the registry does not post comparative estimates or uncertainty intervals. The study therefore offers a descriptive snapshot of safety events alongside its pharmacokinetic summaries, rather than a definitive ranking of treatment safety.

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 registry record leaves several design and analysis details unreported. It identifies the study as randomized, open-label, and crossover, but does not describe randomization procedures, treatment sequence, washout interval, or the statistical model used for the repeated treatment observations. Without this information, it is not possible to assess how period, sequence, or possible carryover effects were addressed.

The primary endpoint values are presented as geometric means and geometric coefficients of variation. The record does not report a formal contrast, confidence interval, p-value, or other estimate of uncertainty for the treatment comparisons. The posted summaries therefore do not show the precision of a difference between treatments. Individual participant data and additional distributional summaries are also not reported.

The registry reports 74 enrolled participants and 69 participants for each primary endpoint treatment summary. It defines an analysis population based on having qualifying reference-treatment data and at least one AMZ001 treatment, but does not explain the reasons participants or measurements were absent from the endpoint summaries. Handling of incomplete treatment periods, missing data, and any sensitivity analyses is not reported in the registry record.

The registry lists secondary outcomes but does not report a multiplicity strategy or indicate which secondary analyses were confirmatory. It also does not report a sample-size justification, interim analyses, or a detailed statistical analysis plan. These omissions limit assessment of how the endpoints and comparisons were selected and how inferential results, if any, were intended to be interpreted.

Safety findings are reported as counts, without event-level timing, comparative uncertainty estimates, or details of follow-up in the information available for this analysis. The study population was healthy participants and the reported treatment period was 7 consecutive days. These features limit how far the safety observations can be extended beyond the study conditions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Bioavailability and Safety Study Comparing Two Dose Levels of AMZ001 and One Dose Level of Diclofenac Sodium 1% Gel in Healthy Participants — NCT05968482.
• Registry record last updated 2025-04-09; status last verified 2025-03.
• Results first posted 2025-04-09.
• 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

The registry describes a completed Phase 1, randomized, open-label, single-center, three-period crossover study in healthy participants. The stated study objective was to compare bioavailability and safety after repeated topical use of AMZ001 at two dose levels and diclofenac sodium 1% gel. AMZ001 was applied once daily for 7 consecutive days; the reference gel was applied four-times daily for 7 consecutive days.

The primary endpoint was Day 7 AUC from time zero to 24 hours, reported as a geometric mean and geometric coefficient of variation. The posted geometric means were 141.5 ng*hr/mL for AMZ001 low dose, 166.1 ng*hr/mL for AMZ001 high dose, and 202.3 ng*hr/mL for diclofenac sodium 1% gel. The endpoint summaries each list 69 participants. The registry does not report formal treatment contrasts or confidence intervals.

Serious adverse event counts were 0 in each treatment group, and deaths were 0 in each group. Other adverse events were reported for 7, 8, and 5 participants in the low-dose AMZ001, high-dose AMZ001, and reference-gel groups, respectively. These are descriptive results; crossover analysis details, missing-data handling, and a detailed statistical plan are not reported in the registry record.