An Open-Label Safety Study of API 31510 in a Topical Cream for in Situ Cutaneous Squamous Cell Carcinoma (SCCIS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Safety Study of API 31510 in a Topical Cream for in Situ Cutaneous Squamous Cell Carcinoma (SCCIS) (NCT00652080), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

In practical statistical terms, the study describes observed safety events among participants treated with API 31510 cream, rather than estimating a treatment effect against a control. With no randomized comparison, the record cannot separate events related to treatment from events that might have occurred for other reasons or under a different care approach. The design also means that apparent changes in disease status cannot be attributed to the cream on the basis of a controlled contrast. The registry’s stated purpose includes preliminary efficacy, but the posted results summarized in this record concern adverse events; a numerical complete-response result is not reported. The central question answerable from the available information is therefore descriptive: what safety event counts were recorded in the study’s treated group during the stated timeframe, and how much uncertainty remains around those counts?

3. Trial Design

NCT00652080 is listed as a completed Phase 1 and Phase 2 study sponsored by BPGbio. Its title describes an open-label safety study of API 31510 in a topical cream for in situ cutaneous squamous cell carcinoma. The registry lists an enrollment of 35 and a single-group model. Allocation is not applicable, and masking is listed as none. The treatment arm is described as Active Cream 3%; AM & PM.

The registry gives a study start of 2008-06 and a primary completion of 2010-01. These dates describe the study record, but do not by themselves establish the duration of treatment or follow-up for every participant. The primary endpoint’s timeframe is six weeks. The record does not report visit schedules, treatment adherence, the timing of individual adverse events, or how long participants were observed beyond that endpoint timeframe.

The primary safety population is defined as all subjects who took at least one dose of the investigational product. The adverse-event record lists a Safety Population with 35 participants at risk for serious events and 35 at risk for other events. The record does not explain whether the same participant-level data were available for every outcome, or whether any participants were excluded from specific analyses.

The study has no like-for-like control group. Because treatment is open-label and all participants are described within one active-treatment arm, the record supports descriptive reporting of events in that arm but not a controlled estimate of the cream’s effect. The registry does not report the protocol’s allocation rationale, a sample-size justification, or a prespecified comparative analysis plan. The study status is completed; completion does not itself indicate that every planned result is posted or that all outcomes have been analyzed in the registry.

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.

Before assignment: Subjects were required to have at least one histologically-confirmed SCCIS lesion that was suitable for excision, ie, to have a lesion with a minimum area of 0.5 cm2 and a maximum diameter of 2.0 cm.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety Population: All subjects who took at least one dose of the investigational product.

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over 6 weeks.

The primary endpoint is the number of participants with adverse events, measured over six weeks. The registry defines the safety population as subjects who took at least one dose of the investigational product. This endpoint is intended to describe the frequency of participants experiencing events during treatment and observation, supporting the stated focus on safety and tolerability of API 31510 cream 3% applied topically to SCCIS.

A participant count is a direct summary: it records how many people experienced an event, rather than how many separate episodes occurred. That distinction matters because a person could have more than one event, while a participant-level endpoint ordinarily counts that person once for the endpoint. The registry record does not detail the event-aggregation rules, such as how recurrent events or multiple event types were handled for the primary endpoint. Nor does it provide a single combined primary-endpoint result in the posted adverse-event summary. Instead, the safety data distinguish serious adverse events from other adverse events.

The endpoint is suitable for describing observed events in a safety-focused study, but it does not establish that API 31510 caused an event. Without a concurrent control group, background illness, underlying SCCIS, and other factors cannot be separated from treatment-associated risks through a between-group comparison. The endpoint also does not measure tumor response. Although percentage of participants with a complete response is listed as a secondary outcome, its numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level measure: whether a participant experienced an adverse event during the stated timeframe. For such an outcome, the basic descriptive quantities are the number of participants with an event and the number at risk, often accompanied by a proportion and an interval expressing uncertainty. The registry identifies the endpoint as a participant count. Its safety summary reports separate serious and other adverse-event categories, rather than one combined participant-level result for the primary endpoint.

What does a participant count capture?

A count of participants with an event differs from a count of event episodes. If one participant experiences repeated episodes, an episode count can be greater than a count of affected participants. Participant-level summaries are useful for understanding how many people were affected at least once, but do not describe recurrence, event duration, severity beyond the category reported, or the total burden of multiple events. The registry record does not describe the detailed rules used to classify or aggregate adverse events for the primary endpoint.

The safety record names a denominator of participants at risk for each reported category. A denominator makes a count easier to interpret in context, but it does not remove uncertainty, establish causation, or guarantee that every participant had identical follow-up. The registry does not report individual follow-up completeness, missing safety observations, or participant-level exposure duration. Thus, the posted counts should be understood alongside the specified six-week endpoint timeframe and the stated safety population, not as a complete account of all possible events over an unspecified longer period.

Why would an interval matter?

A confidence interval is a general statistical tool for showing the range of estimates reasonably compatible with observed data under a specified model and assumptions. It communicates precision, not the probability that a particular treatment is effective, and it does not correct for bias or lack of a control group. When event counts are limited, intervals can be broad even if the point estimate appears straightforward. No confidence interval for the posted adverse-event counts is reported in the registry record, so the precision of those counts is not quantified there.

A comparative analysis would ordinarily require a treatment contrast and a statistical method suited to the outcome and design. This trial has a single group and no concurrent control. A between-arm risk difference or ratio therefore cannot be estimated from the registry record. General methods for comparing two groups do not create a valid comparator where none was enrolled. The registry’s sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions are not a description of this study’s single-group design or evidence that such a design had a particular level of power. No numerical planning results are reported in this record.

The registry indicates no analysis records for the posted outcomes. This should be read narrowly: the registry does not report a formal analysis result in its analysis record. It does not establish whether analyses were performed outside the registry or how they were conducted. The statistical plan, including any adjustment, model choice, or prespecified handling of multiple outcomes, is not reported in the registry record.

How should the event categories be read?

Serious adverse events and other adverse events are separate reporting categories. They should not be combined unless the record defines a combined participant-level endpoint and explains how overlap is handled. A participant may potentially appear in more than one category, and the registry does not state whether categories are mutually exclusive. For that reason, adding category counts would not yield a defensible overall number of affected participants. The serious-event term listing is also a descriptive label, not a statistical comparison or a statement about causality.

For a binary outcome, over-dispersion is not the central issue in the same way it can be for count data with variable event rates. Over-dispersion is a general concern when observed count variability exceeds what a simple model assumes; ignoring it can make uncertainty appear too small. Here, the posted endpoint is participant-based, and event-level recurrence details are not given. There is not enough information to assess a model for recurrent event counts, and no such model is reported. The most appropriate statistical reading remains descriptive, with careful attention to the population, timeframe, and absence of a comparator.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and identifies percentage of participants with a complete response as a secondary outcome. A numerical result for that outcome is not reported in the registry record. The primary endpoint is the number of participants with adverse events over six weeks, but the record does not report a statistical analysis plan describing how the primary and secondary outcomes were to be prioritized or analyzed.

When a study evaluates multiple outcomes, the chance of at least one apparently notable finding can increase if each outcome is tested separately without accounting for the number of comparisons. This is a general statistical concern, not a claim that a particular adjustment was or was not used in this study. The registry record does not report a multiplicity strategy, prespecified hierarchy, or inferential tests for the listed outcomes. The analysis records are absent from the registry.

Missing-data handling is also not reported. The safety population is defined by receipt of at least one dose, but the record does not describe whether all members completed the six-week observation period, how missing adverse-event information was addressed, or whether any imputation was used. It does not report missingness for the secondary complete-response outcome either. Without those details, it is not possible to assess whether the posted results reflect complete observation for every participant or whether exclusions could have influenced the summaries.

The registry does not report a separate analysis population for efficacy or a method for handling participants who did not complete treatment. These omissions do not show that missing data or multiplicity affected the results; they mean that the registry record does not allow those issues to be evaluated. Interpretations should therefore remain limited to the reported safety counts and should not imply a formal confirmatory analysis of efficacy.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pancreatitis (2.9%).

The serious adverse-event entry lists 1 participant in the Safety Population, with 35 participants at risk. The record also lists 22 participants for other adverse events, with 35 at risk. These are separate reported categories; they should not be summed to create an overall adverse-event count because the record does not state whether the categories overlap or how the primary endpoint’s combined result was derived.

Pancreatitis appears in the serious-event term listing at 2.9%. That percentage is a registry-reported value. It does not indicate whether the event was judged related to API 31510, and no causality assessment is reported in the record. Deaths are not reported in the registry record.

Seriousness is a reporting classification and should not be confused with treatment attribution. An event occurring during a study is not automatically caused by the study treatment. Because this was an open-label, single-group study without a concurrent control, the registry cannot establish whether the frequency of the events differed from what would have occurred in another treatment group or without the cream. Event counts describe what was recorded in the study, not the comparative safety profile of API 31510.

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

The record establishes that NCT00652080 was a completed, open-label, single-group study of API 31510 topical cream in SCCIS, with safety and tolerability as its primary focus. The primary safety timeframe was six weeks. The registry lists 1 participant with a serious adverse event and 22 participants for other adverse events, with 35 participants at risk in each category. It also lists pancreatitis at 2.9% among the top serious terms. These observations describe the reported safety experience in the study population.

They do not establish that API 31510 caused or prevented any event. With no concurrent comparator, observed event counts cannot be contrasted with events under placebo, usual care, or another treatment. The open-label design also means the study does not provide a masked comparison. The registry record does not report a confidence interval for the safety counts, so the precision of those estimates is not quantified there.

The study’s stated purpose included obtaining preliminary efficacy data, and complete response is listed as a secondary outcome. However, the result for complete response is not reported in the registry record. No conclusion about the frequency of response or the treatment’s efficacy can be drawn from that missing result. Nor does the fact that the study is completed imply that every planned outcome or analysis has been posted.

The findings are therefore best understood as descriptive safety information from a small, uncontrolled study, not as proof of comparative benefit or harm. The registry does not report the protocol’s statistical plan, a sample-size justification, missing-data handling, or a multiplicity strategy. Those details would be important for evaluating how the study was designed to answer its questions and how robustly its outcomes were analyzed. The available record supports a bounded account of what was reported, while leaving key questions about causal interpretation, precision, and efficacy unresolved.

13. Why This Trial Matters Statistically

This study illustrates why the design and reporting context matter as much as an event count. The registry gives safety counts for a single treatment group, but the same counts would have a different inferential meaning in a randomized comparison. Without a control group, it is not possible to tell from this study whether the observed frequency of adverse events is higher, lower, or similar to a counterfactual treatment experience. The event counts remain useful descriptions, but they are not comparative estimates.

The record also highlights the distinction between event categories and an overall participant-level endpoint. Serious events and other events are reported separately, and the record does not explain whether participants could occur in both categories. Treating categories as if they were mutually exclusive, or adding them to create a total, could misrepresent the number of people affected. Clear definitions and transparent event-aggregation rules are important when interpreting safety endpoints.

Precision should be considered alongside the observed counts. A count without an interval does not show how uncertain an underlying event frequency may be, especially in a study with 35 participants at risk. The registry does not report confidence intervals for these results. This limits the ability to judge how precisely the observed summaries estimate safety frequencies in a broader population.

Finally, the registry’s listed secondary complete-response outcome has no result reported in the record. A stated efficacy objective and a listed outcome are not substitutes for an analyzed result. The case demonstrates the value of complete outcome reporting, including the analysis plan, missing-data approach, and outcome-specific estimates. These statistical features determine what can be learned from a study, and what remains unresolved when only descriptive safety entries are available.

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 main limitation is the single-group design. There is no concurrent control, so the observed adverse-event counts cannot be interpreted as a comparative treatment effect. The open-label status further means masking was absent. These features restrict causal inference regardless of how clearly the counts are reported.

The safety results are presented as separate serious and other adverse-event categories, with no combined participant-level primary-endpoint result in the registry summary. The record does not state whether the categories overlap, how events were grouped, or how recurrent events were handled. The serious-event term listing names pancreatitis at 2.9%, but the record does not report event-level timing, duration, outcome, or treatment relatedness. Deaths are not reported in the registry record.

Although the safety population is defined as participants who took at least one dose, the registry does not report adherence, individual follow-up completeness, or the handling of missing safety data. The six-week timeframe is stated for the primary endpoint, but follow-up beyond that period is not described in the outcome information. A confidence interval for the safety counts is not reported, limiting direct assessment of precision.

The complete-response outcome is listed as secondary, but its result is not reported in the registry record. The analysis plan, sample-size justification, multiplicity handling, and any missing-data methods are also not reported. The registry lists no analysis records for the posted outcomes. These omissions limit interpretation, but they do not establish that analyses were not conducted elsewhere or that the results are biased. They identify what cannot be evaluated using this registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Open-Label Safety Study of API 31510 in a Topical Cream for in Situ Cutaneous Squamous Cell Carcinoma (SCCIS) — NCT00652080.
• Registry record last updated 2019-03-05; status last verified 2019-02.
• Results first posted 2019-02-15.
• 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

NCT00652080 is a completed Phase 1 and Phase 2, open-label, single-group study sponsored by BPGbio. It enrolled 35 participants with squamous cell carcinoma and evaluated API 31510 topical cream, described as Active Cream 3%; AM & PM. The registry lists a study start of 2008-06 and a primary completion of 2010-01.

The primary endpoint is the number of participants with adverse events over six weeks in a safety population defined by receipt of at least one dose. The registry lists 1 participant with a serious adverse event and 22 for other adverse events; each category has 35 participants at risk. Pancreatitis is listed among the top serious terms at 2.9%. Deaths are not reported in the registry record.

Complete response is listed as a secondary outcome, but its result is not reported. No control group, confidence intervals, statistical analysis plan, or missing-data methods are reported in the registry record. The available safety figures are descriptive and do not establish comparative safety or efficacy.