This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Comparison of Diclofenac Systemic Exposure From Two Different Products (AMZ001 and Diclofenac Diethylammonium 1.16% Gel) in Healthy Participants After Repeated Topical Administrations for 7 Days. (NCT06729073), a randomized phase 1 study. The primary outcome is Area Under the Curve 0-24h.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT06729073 |
| Phase | Phase 1 |
| Condition | Healthy Volunteer |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 34 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Amzell |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled healthy participants, rather than patients being treated for a clinical condition. The registry records an enrollment of 34. The posted results describe observations for 33 participants in the AMZ001 group and 34 in the diclofenac diethylamine 1.16% group; these arm entries should not be added to infer a count of distinct participants in a crossover study.
Intervention
AMZ001 was diclofenac sodium gel applied once daily on each knee for 7 consecutive days. The study’s stated aim included assessing its systemic bioavailability after repeated administration, as well as its safety and local tolerability. The registry identifies the study as Phase 1.
Comparator
The reference product was diclofenac diethylamine gel 1.16%, applied four times daily on each knee for 7 consecutive days. The comparison therefore concerns the products as used in these different regimens; product and application schedule are not varied independently in the registry description.
Primary question
On Day 7, what systemic diclofenac exposure was observed over the 0-24h interval with each regimen? The primary endpoint is the area under the concentration-time curve from time zero to 24 hours. The registry reports a geometric mean and geometric coefficient of variation for each arm, but no primary comparative estimate or confidence interval.
3. Trial Design
This was a Phase 1, randomized, open-label, single-center, two-period, two-treatment crossover study. In a crossover design, participants receive each of the treatments in separate periods, so treatment observations can be compared within a participant. Randomization concerns the assigned treatment sequence; the registry does not report the sequence details. It also does not report the length of any interval between periods or other period-specific procedures.
The two regimens were AMZ001, diclofenac sodium gel applied once daily on each knee, and diclofenac diethylamine gel 1.16% applied four times daily on each knee. Both were used for 7 consecutive days. Because both the product and the application frequency differ, the registry comparison is between these treatment regimens as a whole. It does not isolate the effect of product formulation from the effect of dosing frequency.
The study was open-label, meaning masking was not used. The registry lists 34 enrolled participants and records 33 for AMZ001 and 34 for the reference product in the primary outcome results. These outcome entries do not establish that each participant contributed usable measurements in every period. The analysis population and the handling of incomplete period data are not reported in the registry record.
The recorded study start was 2024-11-29, and primary completion was 2025-06-10. The registry status is completed. The sponsor is Amzell. These design details describe how the study was structured; they do not by themselves establish whether the treatment comparison was precise or how any observed difference should be interpreted.
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.
1
| Stage | AMZ001/Diclofenac Diethylamine 1.16% | Diclofenac Diethylamine 1.16%/AMZ001 |
|---|---|---|
| STARTED | 17 | 17 |
| COMPLETED | 17 | 17 |
| NOT COMPLETED | 0 | 0 |
2
| Stage | AMZ001/Diclofenac Diethylamine 1.16% | Diclofenac Diethylamine 1.16%/AMZ001 |
|---|---|---|
| STARTED | 17 | 16 |
| COMPLETED | 17 | 16 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | AMZ001/Diclofenac Diethylamine 1.16% | Diclofenac Diethylamine 1.16%/AMZ001 | Total |
|---|---|---|---|---|
| Participants analysed | 17 | 17 | 34 | |
| Age, Continuous | years | 47.2 (SD 12.75) | 44.5 (SD 9.94) | 45.8 (SD 11.34) |
| Sex: Female, Male: Female | Participants | 11 | 7 | 18 |
| Sex: Female, Male: Male | Participants | 6 | 10 | 16 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 17 | 15 | 32 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 17 | 17 | 34 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Curve 0-24h, measured over Day 7.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | h*ng/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the area under the diclofenac concentration-time curve from time zero to 24 hours, measured on Day 7 and expressed in h*ng/mL. In general, an area-under-the-curve measure summarizes drug concentration over a specified interval. It is used to characterize systemic exposure, rather than a clinical benefit or symptom outcome. The 0-24h interval corresponds to the stated daily observation period for the once-daily AMZ001 regimen.
The registry reports geometric means of 281.6 for AMZ001 and 411.4 for diclofenac diethylamine 1.16%. It also reports geometric coefficients of variation of 67.1% and 57.2%, respectively. A geometric mean summarizes measurements on a multiplicative scale, which is often suitable for pharmacokinetic values that vary proportionally. The geometric coefficient of variation describes variability on that scale; it is not a confidence interval for the treatment contrast.
These group summaries describe measured exposure, but they do not by themselves quantify the uncertainty in the comparison. The registry record does not report a primary treatment contrast, its confidence interval, or a primary comparison p-value. The clinical and statistical interpretation therefore needs to remain tied to the posted summaries and their limitations.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
On Day 7, the posted geometric mean area under the curve from time zero to 24 hours was 281.6 h*ng/mL for AMZ001 and 411.4 h*ng/mL for diclofenac diethylamine 1.16%. The corresponding geometric coefficients of variation were 67.1% and 57.2%. These are descriptive summaries of systemic exposure under the two regimens used in the study.
The registry does not provide a direct primary comparison estimate or a confidence interval for that estimate. Without those quantities, the uncertainty around the treatment contrast cannot be read from the two geometric means alone. In a crossover study, the within-participant relationship between measurements can matter to the precision of a comparison. The posted group summaries do not show that relationship, and no primary comparative analysis is reported in the registry record. The relative precision of the observed primary result is therefore not established by the listed means and variability measures.
The secondary application-site-reaction outcome reports zero participants for AMZ001 and one for the reference product. Its unadjusted risk difference is 0.029, with a 95% confidence interval from -0.027 to 0.086 and p = 0.321. The interval includes zero, so the data are compatible with no difference as well as with differences in either direction within the interval. The p-value is not evidence that the treatments are identical, and the estimate is not a substitute for the primary systemic-exposure comparison.
The primary endpoint addresses systemic exposure, while application-site reactions concern local tolerability. They answer different questions and should not be combined into a single conclusion. In particular, a descriptive exposure contrast does not establish a clinical outcome, and a sparse local-reaction result does not resolve the precision of the primary endpoint.
All interpretation is bounded by the study population and regimen. Participants were healthy, the treatment period was 7 days, and the reference product was applied more frequently than AMZ001. The registry does not report a primary comparative confidence interval, analysis population, or missing-data approach. Consequently, the posted primary summaries support a description of measured exposure but not a precise estimate of the treatment contrast or conclusions beyond the study conditions.
9. Statistical Methods Explained
The endpoint summaries and the design each affect what can be inferred. The registry identifies the primary measure as a geometric mean and reports geometric coefficients of variation. It also identifies the study as a randomized crossover. Those features are relevant to interpretation, but they do not disclose the full statistical analysis plan. Details such as the model used for the primary comparison, any adjustment for period or sequence, and the method for constructing a confidence interval are not reported in the registry record.
What does a geometric mean describe?
In general, a geometric mean is calculated on a logarithmic scale and then expressed back on the original measurement scale. This approach is commonly used when measurements vary multiplicatively: a value that is proportionally higher is treated differently from an equal-sized additive change. The geometric mean is a summary of the observed distribution, not an estimate of a treatment difference by itself. The registry reports 281.6 h*ng/mL for AMZ001 and 411.4 h*ng/mL for diclofenac diethylamine 1.16% on Day 7.
The geometric coefficient of variation summarizes dispersion relative to the geometric mean. In general, it can help convey how spread out pharmacokinetic measurements are on a multiplicative scale. It does not describe the precision of the treatment contrast, and it is not interchangeable with a standard deviation or confidence interval. The registry reports 67.1% for AMZ001 and 57.2% for the reference product. A confidence interval for the primary contrast would address uncertainty in that contrast; none is reported in the registry record.
Why does the crossover design matter?
In general, a crossover design measures each participant under more than one treatment condition. Comparing measurements within the same participant can account for some stable differences between people, but the quality of that comparison depends on the data collected in each period and the analysis used. Period effects, sequence effects, carryover, and incomplete observations may be relevant considerations in crossover studies. Their presence, assessment, or handling in this study is not reported in the registry record, so none should be assumed.
The registry describes randomization, two periods, two treatments, and no masking. It does not report a primary model or state whether the primary analysis used paired observations, adjusted for period, or used another approach. The listed arm-level geometric means and coefficients of variation cannot reconstruct such an analysis. The primary result should therefore be read as posted descriptive summaries, not as a recalculated treatment effect.
What does a confidence interval contribute?
In general, a confidence interval gives a range of values compatible with the data under the assumptions of the analysis. For a treatment contrast, it communicates both the estimated direction and the uncertainty around the estimate. A narrow interval indicates greater statistical precision than a wide one, although precision does not by itself establish clinical importance. The primary endpoint has no reported contrast interval in the registry record, so its comparative precision cannot be assessed from the available primary summaries alone.
The secondary application-site-reaction comparison does have a reported interval: the unadjusted risk difference is 0.029, with a 95% confidence interval from -0.027 to 0.086. This is a separate binary outcome. Its interval includes zero, and its limits also allow nonzero differences. It does not establish equivalence, and it should not be used as a measure of uncertainty for the primary pharmacokinetic endpoint.
How should the planning illustrations be read?
In general, sample-size calculations estimate how many observations a future study might require under specified assumptions. The registry describes its planning illustrations as based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the completed study had a particular probability of detecting an effect. The registry’s planning assumptions do not replace a documented original sample-size justification, which is not reported in the registry record.
The calculation approach also cannot remedy uncertainty in the primary comparison. If the underlying effect estimate or its variance is uncertain, planning values derived from it inherit that uncertainty. The registry does not report a rationale for the original enrollment target, the variance assumptions used in the original design, or an interim-analysis plan. Those details should not be inferred from planning illustrations based on posted results.
What can be recalculated from the posted summaries?
For a binary outcome, an unadjusted risk difference compares the observed proportions in the two groups. In general, its confidence interval reflects uncertainty in that simple comparison, but may not account for design features such as pairing in a crossover study. The registry labels the application-site-reaction contrast as unadjusted and reports p = 0.321. No adjustment for multiplicity is reported. The registry record lists no reported analyses for the secondary outcomes, and the analysis details needed to reproduce or verify a design-adjusted analysis are not reported.
Overall, statistical methods should be distinguished from the numerical summaries. The record supplies endpoint definitions and selected descriptive and secondary comparison results, but not enough detail to establish how the primary contrast was analyzed. General statistical concepts can explain what these summaries mean; they cannot fill in unreported analysis decisions.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report whether the statistical plan controlled the overall type I error across multiple outcomes or comparisons. This matters because examining multiple outcomes can increase the chance of at least one apparently unusual result under a setting where there is no true difference. In general, multiplicity can be addressed through prespecified testing hierarchies, adjusted significance thresholds, or other methods. No such approach is reported for this study.
The available application-site-reaction comparison is explicitly unadjusted, with p = 0.321. It should be understood as a single unadjusted secondary analysis, rather than as a multiplicity-adjusted confirmatory result. The registry lists other secondary pharmacokinetic outcomes, but does not report analyses for them. The number of outcomes alone does not reveal which hypotheses were prespecified, how they were ordered, or whether any correction was planned.
Missing-data handling is not reported in the registry record. The primary result lists 33 observations for AMZ001 and 34 for diclofenac diethylamine 1.16%, while enrollment is listed as 34. These entries do not explain why the primary outcome counts differ, whether measurements were missing in one period, or how any incomplete data were treated. No imputation method, complete-case rule, or sensitivity analysis is reported.
The analysis population is also not reported in the registry record. It is therefore unclear from the posted results whether the primary summaries include all randomized participants, only those with evaluable measurements, or another population. The registry lists no reported analyses for secondary outcomes beyond the posted application-site-reaction comparison. Without these details, readers cannot assess the possible influence of missing observations or determine how closely the analyses follow any prespecified plan.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| AMZ001 | 0 | 33 | 0.0% |
| Diclofenac Diethylamine 1.16% | 0 | 34 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| AMZ001 | 0 of 33 |
| Diclofenac Diethylamine 1.16% | 0 of 34 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| AMZ001 | 5 of 33 |
| Diclofenac Diethylamine 1.16% | 8 of 34 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AMZ001 | Diclofenac Diethylamine 1.16% |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 2 of 33 | 3 of 34 |
| Headache | Nervous system disorders | 1 of 33 | 2 of 34 |
| Rhinitis | Infections and infestations | 0 of 33 | 1 of 34 |
| Urinary tract infection | Infections and infestations | 1 of 33 | 0 of 34 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 33 | 0 of 34 |
| Skin abrasion | Injury, poisoning and procedural complications | 0 of 33 | 1 of 34 |
| Dysuria | Renal and urinary disorders | 0 of 33 | 1 of 34 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 33 | 0 of 34 |
| Erythema | Skin and subcutaneous tissue disorders | 0 of 33 | 1 of 34 |
The registry reports zero serious adverse events for AMZ001 among 33 participants at risk and zero for diclofenac diethylamine 1.16% among 34 participants at risk. It also records zero deaths in each group. These entries describe what was reported during the study; they do not establish that serious events are impossible or rule out uncommon harms.
Safety interpretation is limited by the study setting and exposure period. Participants were healthy, and the repeated topical dosing period was 7 days. The registry’s serious-event counts cannot describe risks during longer use or in patient populations not studied. The record does not provide additional detail in the serious-event terms list.
The registry separately records other adverse events, which are distinct from serious adverse events. A zero count for serious events should not be read as a zero count for all adverse events. These safety entries are descriptive observations from this study and are not a basis for medical advice or a general safety conclusion.
12. What the Result Does, and Does Not, Mean
The primary result describes systemic diclofenac exposure after the specified topical regimens in healthy participants. It reports Day 7 geometric mean area-under-the-curve values and their geometric coefficients of variation. This gives readers information about the measured exposure summaries, but the registry does not report a primary treatment contrast with a confidence interval. The statistical precision of the comparative result is therefore not established by the posted primary values alone.
The two study regimens differ in both product and application frequency: AMZ001 was applied once daily on each knee, whereas the reference product was applied four times daily on each knee. Any observed contrast pertains to these regimens as studied. The design does not, from the registry description alone, separate a formulation effect from a frequency-of-application effect.
The endpoint is pharmacokinetic, not a measure of symptom relief, function, or another clinical outcome. The registry record does not report evidence about clinical effectiveness. The findings also do not establish longer-term safety: the study involved healthy participants and repeated administration for 7 days. Results from this setting should not be extended to patients, other durations, or other patterns of use without evidence.
The secondary application-site-reaction comparison offers limited additional context. Its unadjusted interval includes zero and spans values on either side, so it does not demonstrate that the regimens have the same local-reaction risk. The registry does not report analyses for the other secondary outcomes. Those gaps limit the conclusions that can be drawn from the secondary results.
In short, the posted data characterize selected exposure and safety summaries under the study conditions. They do not supply a complete estimate of the primary comparative effect, establish equivalence, or answer broader clinical questions. Those distinctions are central to interpreting a small, short Phase 1 pharmacokinetic study.
13. Why This Trial Matters Statistically
This study illustrates why the choice of endpoint matters. Area under the concentration-time curve describes systemic exposure, while a clinical outcome would address a different question. A pharmacokinetic result can characterize how much drug reaches systemic circulation over a defined interval, but it does not by itself establish a clinical benefit or harm.
It also illustrates the importance of matching interpretation to design. In a crossover study, the comparison may draw on within-participant information, yet the registry reports only group-level geometric means and variability for the primary outcome. Without a reported comparative estimate and confidence interval, readers cannot assess the precision of the primary contrast. Design labels alone do not reveal the analysis details needed to understand that precision.
The regimens make the estimand especially important. The products differ, and their application frequencies differ as well. The resulting comparison concerns the full regimens rather than an isolated formulation effect. A clear description of what is being compared prevents the numerical contrast from being attributed to a single feature that the study did not vary independently.
Finally, the registry record demonstrates why secondary and safety results need context. An unadjusted secondary comparison may be informative but carries less weight when many outcomes may be examined and no multiplicity approach is reported. Zero serious adverse events in the posted groups is a description of the study observations, not proof that serious events cannot occur. These are general lessons in distinguishing observed data, statistical uncertainty, and the scope of a study’s conclusions.
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.
Several limitations specific to this study constrain interpretation. The participants were healthy, so the record does not directly describe exposure or tolerability in people being treated for a medical condition. The study evaluated repeated administration for 7 days, which does not establish what might be observed with longer use.
The treatment regimens differed in both product and application frequency. AMZ001 was used once daily on each knee, while the reference product was used four times daily on each knee. The comparison therefore cannot isolate a product-only difference from a dosing-schedule difference on the basis of the registry description.
The study was open-label and single-center. The registry does not report whether awareness of treatment could have influenced outcome collection, or how any such possibility was addressed. For the primary outcome, the record provides group geometric means and geometric coefficients of variation but no comparative estimate, confidence interval, or p-value. That omission prevents a direct assessment of the primary comparison’s statistical precision.
The registry also does not report the primary analysis population, the statistical model, missing-data handling, period or sequence adjustments, or the approach to multiplicity. Primary outcome counts are listed as 33 for AMZ001 and 34 for the reference product, but the record does not explain the difference. Analyses for most listed secondary outcomes are not reported. These limits leave important questions about analysis and completeness unresolved.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Comparison of Diclofenac Systemic Exposure From Two Different Products (AMZ001 and Diclofenac Diethylammonium 1.16% Gel) in Healthy Participants After Repeated Topical Administrations for 7 Days. — NCT06729073.
- Registry record last updated 2026-01-06; status last verified 2025-12.
- Results first posted 2026-01-06.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT06729073 is a completed Phase 1, randomized, open-label, single-center, two-period, two-treatment crossover study sponsored by Amzell. It enrolled 34 healthy participants. The recorded study start was 2024-11-29, and primary completion was 2025-06-10.
The study compared AMZ001, diclofenac sodium gel applied once daily on each knee, with diclofenac diethylamine gel 1.16% applied four times daily on each knee. Both regimens were used for 7 consecutive days. The primary endpoint was the Day 7 area under the curve from time zero to 24 hours.
The registry reports geometric mean exposure summaries and geometric coefficients of variation for the primary outcome, but no primary comparative estimate or confidence interval. It also reports an unadjusted application-site-reaction comparison and zero serious adverse events and deaths in each group. The analysis population, primary analysis details, missing-data handling, and multiplicity plan are not reported in the registry record.