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 Safety and Efficacy of Escalating Doses of LEO 43204 Applied Once Daily for Two Consecutive Days on Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis (NCT02120456), a randomized phase 1, phase 2 study. The primary outcome is Part 1: Participants Experiencing Dose Limiting Toxicity (DLT) Based on Local Skin Responses (LSRs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02120456 |
| Phase | Phase 1, Phase 2 |
| Condition | Actinic Keratosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 224 |
| Arms in the primary outcome | n/a |
| Lead sponsor | LEO Pharma |
| Results posted | Yes |
2. Clinical Question
Population
People with actinic keratosis treated on the trunk and extremities. The title specifies an application area of approximately 250 cm2. Further eligibility details and the characteristics of participants enrolled are not reported in the registry record.
Intervention
LEO 43204 gel applied once daily for two consecutive days. Part 1 used escalating doses, and Part 2 evaluated doses of 0.075% and 0.1%.
Comparator
Part 2 compared the LEO 43204 dose groups with vehicle gel, described in the registry as placebo. Part 1 is described as an open-label dose-escalation assessment rather than a vehicle-controlled comparison.
Primary question
In Part 1, how many participants experienced dose-limiting toxicity based on local skin responses, and which dose met the stated maximum tolerated dose definition? Part 2 was intended to evaluate efficacy against vehicle, but efficacy results are not reported in the registry record.
The registry describes a two-part investigation rather than a single comparison with one shared purpose. Part 1 focused on tolerability across escalating doses: its stated purpose was to identify maximum tolerated dose levels after the brief application regimen. Part 2 evaluated efficacy at two selected doses against vehicle. The listed primary outcome, however, is the Part 1 count of participants with dose-limiting toxicity, not an efficacy comparison.
This distinction matters when interpreting the record. A question about whether participants had complete or partial clearance of actinic keratoses belongs to the listed secondary outcomes for Part 2. The registry names those outcomes but does not report their results. The central question that can be described from the primary outcome definition is therefore how dose-limiting toxicity was defined and counted, not whether the treatment produced clearance.
The registry identifies the condition and treatment schedule, but does not report the full eligibility criteria, baseline disease characteristics, or the clinical rationale for selecting the treatment area. Those details would help clarify how closely the enrolled population and application conditions match other clinical settings. Without the primary endpoint results, the record does not establish which dose, if any, met the maximum tolerated dose criterion.
3. Trial Design
The registry describes NCT02120456 as a randomized, quadruple-masked, parallel Phase 1 and Phase 2 trial. Enrollment is listed as 224, and the status is completed. The recorded start was 2014-05 and primary completion was 2015-05. The sponsor is LEO Pharma. These registration details describe the overall study, while the arm descriptions show that the study had distinct parts with different purposes.
Part 1 was an open-label dose-escalation assessment. The listed gel concentrations were 0.018%, 0.025%, 0.037%, 0.05%, 0.075%, and 0.1%. Each dose group was described as receiving treatment once daily for two consecutive days. The registry states that this part was intended to identify maximum tolerated dose levels using dose-limiting toxicity based on local skin responses. Its open-label description means masking should not be assumed for this part, even though the overall record lists quadruple masking.
Part 2 evaluated LEO 43204 at 0.075% and 0.1% against vehicle gel. The listed arms describe once-daily treatment for two consecutive days. This part's stated purpose was efficacy evaluation, and the listed secondary outcomes concern complete and partial clearance of actinic keratoses. The registry does not report the allocation ratio, the method used to generate or conceal the random sequence, or which roles were masked in the parts of the trial.
The title describes application on approximately 250 cm2 on the trunk and extremities. The record identifies placebo as an intervention and describes the Part 2 control arm as vehicle gel. It does not report additional details about treatment adherence, concurrent care, follow-up beyond the stated primary endpoint timeframe, or the study protocol. Although the overall design is described as randomized and parallel, those labels alone do not resolve how procedures differed between the dose-escalation and vehicle-controlled parts.
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.
Only the first 6 of 9 groups are shown.
Part 1 Open-label, Dose-escalation Phase
| Stage | Part 1: LEO 43204 Gel 0.018% | Part 1: LEO 43204 Gel 0.025% | Part 1: LEO 43204 Gel 0.037% | Part 1: LEO 43204 Gel 0.05% | Part 1: LEO 43204 Gel 0.075% | Part 1: LEO 43204 Gel 0.1% |
|---|---|---|---|---|---|---|
| STARTED | 12 | 12 | 12 | 12 | 12 | 9 |
| COMPLETED | 12 | 12 | 12 | 12 | 12 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Part 2 Double-blind Phase
| Stage | Part 1: LEO 43204 Gel 0.018% | Part 1: LEO 43204 Gel 0.025% | Part 1: LEO 43204 Gel 0.037% | Part 1: LEO 43204 Gel 0.05% | Part 1: LEO 43204 Gel 0.075% | Part 1: LEO 43204 Gel 0.1% |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Part 1: LEO 43204 Gel 0.018% | Part 1: LEO 43204 Gel 0.025% | Part 1: LEO 43204 Gel 0.037% | Part 1: LEO 43204 Gel 0.05% | Part 1: LEO 43204 Gel 0.075% | Part 1: LEO 43204 Gel 0.1% |
|---|---|---|---|---|---|---|
| Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrawal of consent | 0 | 0 | 0 | 0 | 0 | 0 |
| Unable to attend visit due to work | 0 | 0 | 0 | 0 | 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.
Only the first 6 of 10 groups are shown.
| Characteristic | Unit | Part 1: LEO 43204 Gel 0.018% | Part 1: LEO 43204 Gel 0.025% | Part 1: LEO 43204 Gel 0.037% | Part 1: LEO 43204 Gel 0.05% | Part 1: LEO 43204 Gel 0.075% | Part 1: LEO 43204 Gel 0.1% |
|---|---|---|---|---|---|---|---|
| Participants analysed | 12 | 12 | 12 | 12 | 12 | 9 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 | 2 | 3 | 4 | 5 | 3 |
| Age, Categorical: >=65 years | Participants | 3 | 10 | 9 | 8 | 7 | 6 |
| Sex: Female, Male: Female | Participants | 4 | 3 | 6 | 6 | 6 | 6 |
| Sex: Female, Male: Male | Participants | 8 | 9 | 6 | 6 | 6 | 3 |
| Region of Enrollment: Canada | participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 12 | 12 | 12 | 12 | 12 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Part 1: Participants Experiencing Dose Limiting Toxicity (DLT) Based on Local Skin Responses (LSRs), measured over From Day 1 up to and including Day 8.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the count of participants in Part 1 who experienced dose-limiting toxicity based on local skin responses. The observation window runs from Day 1 up to and including Day 8. The endpoint was intended to support identification of the maximum tolerated dose after once-daily treatment for two consecutive days.
The registry defines dose-limiting toxicity using severe local response grades or investigator judgment. A participant met the listed definition with one or more of the specified local skin responses at Grade 4, or with two or more of the specified responses at the listed Grade 3 or Grade 4 levels. The definition also includes other clinically relevant signs or symptoms that the investigator judged should count as dose-limiting toxicity. The maximum tolerated dose was defined as the highest dose level at which less than 4 out of 12 participants experienced a dose-limiting toxicity.
Local skin responses were assessed across six categories: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. Each category had a numeric severity grade from 0 to 4, with Grade 0 indicating no presence and Grade 4 the highest severity. The endpoint is a participant count, not a mean severity score. It is used because the stated Part 1 aim is dose selection based on toxicity, but the registry record does not report the observed dose-limiting toxicity counts or the dose identified by this rule.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry provides the structure and definitions needed to understand the primary endpoint, but it does not report the primary endpoint results. In particular, the record does not give the number of participants experiencing dose-limiting toxicity at each Part 1 dose, nor does it state which dose met the maximum tolerated dose definition. The dose threshold in the endpoint definition should not be mistaken for an observed result.
Part 2 was intended to compare two LEO 43204 doses with vehicle for efficacy. Complete clearance and partial clearance are listed as secondary outcomes, with last observation carried forward named in their descriptions. The registry record does not report the numbers of participants with either outcome, comparative estimates, confidence intervals, or statistical tests for these efficacy outcomes. Consequently, no conclusion about the magnitude or precision of an efficacy difference can be drawn from the posted results described in this record.
The available adverse-event counts are descriptive. In Part 1, the registry lists no participants with serious adverse events in each of the dose groups. For other adverse events, it lists affected-participant counts of 3, 3, 5, 9, 10, and 7 in the respective 0.018%, 0.025%, 0.037%, 0.05%, 0.075%, and 0.1% groups. In Part 2, the vehicle group has 0 participants listed with serious adverse events and 6 with other adverse events; the 0.075% group has 1 and 36, respectively; and the 0.1% group has 2 and 39, respectively. These are counts, and should not be read as comparative estimates of risk or as evidence of a causal relationship.
The serious adverse-event terms listed by the registry are urinary tract infection at 1.7%, keratoacanthoma at 1.6%, and squamous cell carcinoma of skin at 1.6%. The record does not identify the participant group for each term in this listing. It also does not explain the denominator or analysis method used for these percentages. The death fields are not reported in the registry record, so no conclusion about deaths can be made from those fields.
General statistical interpretation: counts convey how many events were recorded, but do not by themselves quantify uncertainty around the underlying event frequency or establish differences between groups. Comparative interpretation requires appropriate estimates and their uncertainty, along with information about the analysis population and methods. Those efficacy and primary-endpoint results are not reported in the registry record.
9. Statistical Methods Explained
General statistical explanation: a binary outcome records whether each participant did or did not experience an event. The primary outcome is expressed as a count of participants with dose-limiting toxicity. Counts are directly interpretable as event totals, but interpretation also depends on how many participants were assessed, how the event was defined, and whether the same methods were applied across groups. Here, the registry supplies the endpoint definition and describes dose groups, but does not report the primary outcome counts.
How the dose-limiting toxicity rule works
The rule combines local response severity with a participant-level threshold. Some single Grade 4 responses are sufficient to meet the definition. The rule also includes specified combinations of at least two responses at Grade 3 or Grade 4. In addition, the investigator could classify other clinically relevant signs or symptoms as dose-limiting toxicity. Thus, the endpoint is not simply a count of participants with any local skin response; it is a count based on the particular severity and combination criteria, plus the specified investigator judgment.
The registry defines the maximum tolerated dose as the highest dose at which less than 4 out of 12 participants experienced a dose-limiting toxicity. That is a decision rule stated for the study, not a result. The record does not provide the observed dose-limiting toxicity counts needed to apply it. Nor does it report how an incomplete group, if any, would have been handled under the rule. A reader therefore cannot determine the maximum tolerated dose from the posted primary endpoint information.
What the local response grades represent
Local skin responses were assessed in six categories, and each category used a severity grade from 0 to 4. A higher grade denotes greater severity according to the registry's description, with Grade 0 indicating no presence and Grade 4 the highest grade. The dose-limiting toxicity definition uses selected grades for particular categories; it does not treat every category or every grade as an event of equal consequence. This is why the operational definition is essential when interpreting the endpoint label.
General statistical explanation: a prespecified threshold can help make dose-escalation decisions consistent by tying them to a defined event rule. Its usefulness depends on applying that rule consistently and reporting the resulting counts by dose. Because the primary outcome counts are not reported in the registry record, neither the rule's application nor its resulting dose decision can be checked from the posted information.
Counts, comparisons, and uncertainty
The adverse-event data are presented as counts of participants affected, with counts at risk also listed for each group. A count is not the same as an estimated treatment effect. A comparison between groups would ordinarily require a clearly defined contrast and a method for expressing uncertainty, such as a confidence interval. A confidence interval is a range of values compatible with the data and the chosen statistical method; its width communicates how precisely an effect has been estimated. Confidence intervals for the primary or efficacy outcomes are not reported in the registry record.
General statistical explanation: small event counts can leave substantial uncertainty about the underlying event frequency, even when the count itself is exact. In dose-escalation settings, safety interpretation also depends on the dosing sequence and the rules used to move between doses. Those operational details are not reported in the registry record beyond the stated dose-limiting toxicity definition and the open-label dose-escalation description. The listed group counts should therefore be read as descriptive registry data, not as a complete account of the dose-selection method.
Planning illustrations and trial design
The record describes a separate 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. The illustration considers effects defined as stated fractions of the observed effect. It is not described as the trial's own design justification. Any sample sizes from such an illustration are planning values, not observed enrollment and not observed power. The registry record does not report the original sample-size justification or establish that the illustration's assumptions were used to design or analyze the trial.
General statistical explanation: a sample-size calculation depends on the outcome, target effect, variability or event frequency, chosen error rate, allocation, and analysis method. A planning calculation can show how assumptions relate to a hypothetical study size, but it cannot demonstrate that a completed study had a particular probability of detecting an effect. No such probability should be inferred from the planning illustration. The reported overall enrollment of 224 is a registry design fact; it does not replace the unreported group-specific primary-outcome results or clarify which participants entered each analysis.
The registry labels the overall study randomized, quadruple-masked, and parallel. Those descriptors do not supply the randomization procedure, the masking roles, the analysis model, or the handling of departures from assigned treatment. These statistical methods are not reported in the registry record. The distinction between Part 1's open-label dose escalation and Part 2's vehicle comparison should be retained when considering which design features apply to each part.
10. Multiplicity, Missing Data and Analysis Populations
The registry describes more than one study purpose and lists multiple outcomes, including the primary Part 1 dose-limiting toxicity outcome and Part 2 complete and partial clearance outcomes. It also lists 9 analyses and 4 outcome measures. A multiplicity strategy for interpreting multiple outcomes, doses, or analyses is not reported in the registry record. It is therefore unclear whether any adjustment was planned or how the family of statistical comparisons was defined. Without that information and without outcome estimates or tests, the record does not support claims about statistical significance across endpoints or dose groups.
The Part 2 secondary outcome descriptions specify last observation carried forward (LOCF). LOCF is a method that uses a participant's last recorded observation as the value for a later assessment when follow-up data are missing. General statistical explanation: this approach can simplify analyses, but its interpretation depends on why observations are missing and whether carrying the last value forward is reasonable for the outcome. The registry does not report the amount or pattern of missing data, the assessment time point used, sensitivity analyses, or how LOCF was applied in detail. It also does not report missing-data procedures for the primary endpoint or adverse-event data.
The analysis populations are not reported in the registry record. There is no description of whether analyses used all randomized participants, participants who received treatment, or another defined group, and no account of exclusions or protocol deviations. The randomized design alone does not identify which participants contributed to each posted outcome. These gaps make it difficult to assess whether outcome counts and comparisons followed the intended allocation or how robust results would be to alternative missing-data assumptions.
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 |
|---|---|---|---|
| Part 1: LEO 43204 Gel 0.018% | 0 | 12 | 0.0% |
| Part 1: LEO 43204 Gel 0.025% | 0 | 12 | 0.0% |
| Part 1: LEO 43204 Gel 0.037% | 0 | 12 | 0.0% |
| Part 1: LEO 43204 Gel 0.05% | 0 | 12 | 0.0% |
| Part 1: LEO 43204 Gel 0.075% | 0 | 12 | 0.0% |
| Part 1: LEO 43204 Gel 0.1% | 0 | 9 | 0.0% |
| Part 2: LEO 43204 Vehicle Gel | 0 | 32 | 0.0% |
| Part 2: LEO 43204 Gel 0.075% | 1 | 60 | 1.7% |
| Part 2: LEO 43204 Gel 0.1% | 2 | 63 | 3.2% |
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 |
|---|---|
| Part 1: LEO 43204 Gel 0.018% | 3 of 12 |
| Part 1: LEO 43204 Gel 0.025% | 3 of 12 |
| Part 1: LEO 43204 Gel 0.037% | 5 of 12 |
| Part 1: LEO 43204 Gel 0.05% | 9 of 12 |
| Part 1: LEO 43204 Gel 0.075% | 10 of 12 |
| Part 1: LEO 43204 Gel 0.1% | 7 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Part 1: LEO 43204 Gel 0.018% | Part 1: LEO 43204 Gel 0.025% | Part 1: LEO 43204 Gel 0.037% | Part 1: LEO 43204 Gel 0.05% | Part 1: LEO 43204 Gel 0.075% | Part 1: LEO 43204 Gel 0.1% |
|---|---|---|---|---|---|---|---|
| Keratoacanthoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 9 |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 9 |
| Urinary tract infection | Infections and infestations | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part 1: LEO 43204 Gel 0.018% | Part 1: LEO 43204 Gel 0.025% | Part 1: LEO 43204 Gel 0.037% | Part 1: LEO 43204 Gel 0.05% | Part 1: LEO 43204 Gel 0.075% | Part 1: LEO 43204 Gel 0.1% |
|---|---|---|---|---|---|---|---|
| Application site pruritus | General disorders | 2 of 12 | 1 of 12 | 4 of 12 | 7 of 12 | 7 of 12 | 6 of 9 |
| Application site pain | General disorders | 2 of 12 | 1 of 12 | 2 of 12 | 6 of 12 | 6 of 12 | 3 of 9 |
| Administration site reaction | General disorders | 1 of 12 | 0 of 12 | 0 of 12 | 1 of 12 | 0 of 12 | 0 of 9 |
| Application site discomfort | General disorders | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 1 of 9 |
| Application site inflammation | General disorders | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 1 of 9 |
| Oedema peripheral | General disorders | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 1 of 9 |
| Tremor | Nervous system disorders | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 1 of 9 |
| Dermatitis | Skin and subcutaneous tissue disorders | 0 of 12 | 1 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 9 |
| Dermatitis contact | Skin and subcutaneous tissue disorders | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 12 | 1 of 12 | 0 of 9 |
| Skin burning sensation | Skin and subcutaneous tissue disorders | 0 of 12 | 0 of 12 | 1 of 12 | 0 of 12 | 0 of 12 | 0 of 9 |
Serious events with the highest arm-level rate: urinary tract infection (1.7%), keratoacanthoma (1.6%), squamous cell carcinoma of skin (1.6%).
The registry lists serious adverse events and other adverse events separately, with the number of participants at risk and the number affected for each arm. These are participant counts. In Part 1, no participants are listed as affected by serious adverse events in the 0.018%, 0.025%, 0.037%, 0.05%, 0.075%, or 0.1% groups. In Part 2, the registry lists 0 affected participants in the vehicle group, 1 in the 0.075% group, and 2 in the 0.1% group. Other adverse events are listed for 3, 3, 5, 9, 10, and 7 participants across the Part 1 dose groups, and for 6, 36, and 39 participants in the Part 2 vehicle, 0.075%, and 0.1% groups, respectively.
These counts do not establish that an event was caused by treatment, nor do they adjust for differences in group size, follow-up, or participant characteristics. The registry's serious-event term listing gives urinary tract infection at 1.7%, keratoacanthoma at 1.6%, and squamous cell carcinoma of skin at 1.6%, but does not specify the group attribution or denominator for these percentages. Deaths are not reported in the registry record. The figures should therefore be read as the registry's safety listings, not as a complete comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, quadruple-masked, parallel Phase 1 and Phase 2 trial was registered as completed, with 224 participants enrolled overall. It describes a brief topical application regimen, a Part 1 dose-escalation assessment, and a Part 2 evaluation of two doses against vehicle. It also gives an operational definition for dose-limiting toxicity and lists adverse-event counts. These details help explain what the investigators set out to study and how the primary safety endpoint was defined.
The record does not report the observed primary endpoint counts or identify the dose that met the stated maximum tolerated dose rule. It also does not report Part 2 complete or partial clearance results, comparative efficacy estimates, confidence intervals, or statistical tests. The stated aims should not be confused with findings: a planned evaluation is not evidence of its result. On the registry information available, the size and precision of any efficacy effect cannot be characterized.
The adverse-event listings describe participants affected in each arm, but counts alone do not tell whether observed events were related to treatment or whether apparent differences are statistically distinguishable from chance. They also do not provide a complete account of event timing, duration, severity, or follow-up. The percentages attached to the listed serious adverse-event terms lack a stated denominator and group attribution in this record, so they should not be used to compare arms.
General statistical explanation: a clinical result is more informative when an effect estimate is accompanied by uncertainty and a transparent account of the analysis population, missing data, and planned comparisons. Those details are not reported in the registry record. The registry therefore supports a description of the trial's design and some safety counts, but not a conclusion about efficacy, a definitive ranking of doses, or a causal interpretation of the adverse events.
13. Why This Trial Matters Statistically
This trial is statistically notable for separating dose selection from an efficacy comparison. Part 1 used an open-label, escalating-dose approach and a threshold-based definition of maximum tolerated dose. Part 2 evaluated two specified doses against vehicle. These distinct aims call for different interpretations: the first concerns a dose-limiting toxicity rule, while the second concerns efficacy outcomes. Treating the record as one simple treatment-versus-control test would obscure that structure.
The primary endpoint illustrates how a clinical outcome depends on its operational definition. It is not any local skin response, but a participant-level classification based on particular grades, combinations of responses, and investigator judgment. A clear definition is necessary for reproducibility, yet results are also needed to see how many participants met the definition at each dose and how the maximum tolerated dose rule was applied. Those counts are not reported in the registry record.
The record also shows why adverse-event counts should be interpreted with restraint. Counts are useful descriptive information, but they do not supply a comparative effect estimate or its uncertainty. The missing primary endpoint and efficacy results further limit cross-part comparisons: the available safety listings cannot answer the study's stated efficacy question. General statistical principle: a trial's design labels and endpoint definitions do not substitute for transparent results, analysis methods, and uncertainty estimates.
Finally, the planning illustration is distinct from the trial's design rationale and from observed results. Keeping planning assumptions separate from actual enrollment and analysis helps avoid treating hypothetical sample sizes as evidence about the completed study's ability to detect an effect. The registry record does not report the original sample-size justification, so the illustration cannot fill that gap.
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 most consequential limitation of the registry record is that it does not report the primary endpoint results. The Part 1 dose-limiting toxicity counts by dose and the dose identified under the maximum tolerated dose rule are not reported in the registry record. This prevents assessment of the stated primary objective from the posted information.
Although Part 2 was intended to evaluate efficacy against vehicle, the complete-clearance and partial-clearance outcomes are listed without their results. Comparative estimates, confidence intervals, statistical tests, and details of the analysis population are also not reported in the registry record. Therefore, neither the size nor precision of any Part 2 treatment difference can be assessed.
Several design and analysis details are absent. Randomization sequence generation and concealment, the roles covered by quadruple masking, group allocation procedures, protocol deviations, and the statistical analysis plan are not reported in the registry record. The open-label description of Part 1 also means that the overall masking label should not be assumed to characterize every study procedure. The record does not give baseline characteristics or explain whether the recorded enrollment corresponds to all randomized participants or another population.
The secondary-outcome descriptions name LOCF, but the missing-data extent, timing, reasons, and sensitivity analyses are not reported. The registry does not specify a multiplicity strategy despite listing multiple outcomes and analyses. Safety counts are available, but the record does not supply event-level context or attribute the serious-event term percentages to particular arms. Death fields are not reported. Together, these omissions limit evaluation of efficacy, dose selection, precision, and comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of Escalating Doses of LEO 43204 Applied Once Daily for Two Consecutive Days on Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis — NCT02120456.
- Registry record last updated 2025-03-06; status last verified 2018-11.
- Results first posted 2019-01-04.
- 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.
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18. Record Summary
NCT02120456 is a completed randomized, quadruple-masked, parallel Phase 1 and Phase 2 trial sponsored by LEO Pharma. The record lists enrollment of 224, a start of 2014-05, and primary completion of 2015-05. It concerns LEO 43204 applied once daily for two consecutive days to an approximately 250 cm2 area on the trunk and extremities of people with actinic keratosis.
Part 1 was an open-label dose-escalation assessment intended to identify maximum tolerated dose using dose-limiting toxicity based on local skin responses. Part 2 evaluated doses of 0.075% and 0.1% against vehicle. Complete and partial clearance are listed as secondary outcomes. The primary endpoint results and Part 2 efficacy results are not reported in the registry record. Adverse-event participant counts are listed, but the record does not provide enough accompanying analysis to establish comparative effects or causal interpretations.