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 Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS) (NCT01350115), a randomized phase 2 study. The primary outcome is Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01350115 |
| Phase | Phase 2 |
| Condition | Basal Cell Carcinoma, Gorlin Syndrome, Nevoid Basal Cell Carcinoma Syndrome |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Adults with nevoid basal cell carcinoma syndrome (NBCCS) were the intended study population. The primary endpoint description refers to participants with main target basal cell carcinomas (BCCs), with secondary target BCCs included as appropriate. The registry describes an analysis population of participants with evaluable or complete pharmacodynamic or biomarker data and no protocol deviations with significant impact on those data. Whether this population was also used for the primary endpoint is not reported in the registry record.
Intervention
Participants assigned to LDE225 received 400 mg orally once daily. The trial description identifies the study as dose-ranging, but the listed active regimen describes this dose; other dose levels are not reported in the registry record.
Comparator
The comparator was matching placebo. The trial was randomized, double-blind, and parallel-group. The allocation ratio and details of how the random sequence was generated or concealed are not reported in the registry record.
Primary question
The primary endpoint was clinical clearance of main target BCCs at Day 113, assessed on a six-point scale ranging from worsening to complete clearance. The study was described as exploratory and intended to demonstrate preliminary efficacy. The registry record does not report the distribution of endpoint scores or an estimated comparison between LDE225 and placebo, so it does not establish how the groups differed on this endpoint.
3. Trial Design
This was a phase II, randomized, double-blind, parallel-group proof-of-concept study of oral LDE225 in adults with NBCCS. The registry lists an enrollment of 10 participants and identifies basal cell carcinoma, Gorlin syndrome, and NBCCS among the conditions studied. Novartis Pharmaceuticals is listed as the sponsor. The trial status is completed, with a start date of 2011-04 and primary completion in 2012-10.
The active treatment was LDE225 at 400 mg once daily; the comparison group received matching placebo. Although the trial title and description call it dose-ranging, the listed active intervention describes one dose. Further dose levels or dose assignment details are not reported in the registry record. The allocation ratio, sequence-generation method, concealment procedures, and details of how masking was maintained are also not reported.
The study description identifies a screening period of approximately 4 weeks, a treatment period of 12 weeks, an initial follow-up of approximately 6-8 weeks, and then long-term follow-up. The primary clearance assessment was scheduled for Day 113. The registry does not specify the duration or assessment schedule of long-term follow-up in the registry record for this analysis.
The study is explicitly characterized as exploratory, with the stated purpose of assessing preliminary efficacy alongside safety and pharmacokinetics. That framing is important when interpreting a small trial: a proof-of-concept study can characterize the feasibility of measuring a response and provide preliminary observations, but its design label alone does not establish the size or precision of any treatment effect. The statistical analysis plan, sample-size justification, and outcome results 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.
Before assignment: Participants were assigned to one of the following 2 treatment arms in a ratio of 6:1,LDE225 400 mg QD and Placebo QD.
Core Study (All Patients)
| Stage | LDE225 | Placebo |
|---|---|---|
| STARTED | 8 | 2 |
| Safety Anlysis Set | 8 | 2 |
| Pharmacodynamic Set | 7 | 2 |
| COMPLETED | 8 | 2 |
| NOT COMPLETED | 0 | 0 |
Long Term Follow-Up (All Patients)
| Stage | LDE225 | Placebo |
|---|---|---|
| STARTED | 8 | 2 |
| COMPLETED | 7 | 0 |
| NOT COMPLETED | 1 | 2 |
Reasons for not completing this period:
| Reason | LDE225 | Placebo |
|---|---|---|
| Lost to Follow-up | 0 | 1 |
| Adverse Event | 0 | 1 |
| Withdrawal by Subject | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants, who had evaluable (or complete) pharmacodynamic (PD) or biomarker parameter data and were without protocol deviations with significant impact on the PD data, were included in the PD analysis set.
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 | LDE225 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 2 | 10 | |
| Age, Continuous | Years | 50.5 (SD 9.90) | 66 (SD 2.00) | 53.6 (SD 10.95) |
| Sex: Female, Male: Female | Participants | 4 | 0 | 4 |
| Sex: Female, Male: Male | Participants | 4 | 2 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs), measured over Day 113.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was clinical clearance assessment of main target BCCs, recorded as a number of participants at Day 113. Investigators compared the clinical presentation at the assessment visit with baseline using a six-point scale: 0 meant worsening; 1, no change; 2, slight clearance (1-25% improvement); 3, moderate clearance (26-75% improvement); 4, marked clearance (76-99% improvement); and 5, complete clearance (100% improvement). Complete clearance meant no clinical residual signs of carcinoma, except for specified post-inflammatory changes or residual scarring.
This graded endpoint distinguishes worsening, stability, and different degrees of improvement rather than treating all responses as the same. In general, a multi-category clinical measure can preserve distinctions that would be lost if outcomes were collapsed into a simple improved/not-improved classification. The scale is based on investigator assessment, and complete clearance has a specific clinical definition in the record.
The primary endpoint results are not reported in the registry record. In particular, no category counts, group comparison, effect estimate, confidence interval, or statistical test for Day 113 is reported. The record’s analysis-population description concerns evaluable pharmacodynamic or biomarker data; whether that definition governed the primary clinical endpoint is not reported.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison of LDE225 and matching placebo, but it does not report the primary endpoint results. The endpoint was a six-category clinical clearance assessment at Day 113. Without participant counts by category or a stated treatment comparison, the record does not show the observed clearance pattern in either group or the magnitude and precision of any difference between groups.
The total enrollment was 10. This small enrollment means that any group estimates, if available, would need to be read with attention to their uncertainty. In general, estimates based on few participants can be imprecise, and a confidence interval communicates the range of values compatible with the data under the analysis assumptions. No confidence interval for the primary endpoint is reported in the registry record. The endpoint categories also matter: a comparison could depend on whether the analysis retained all six categories or combined some of them. The analysis method and any such grouping are not reported.
The record calls the trial exploratory and proof-of-concept. That wording describes the stated study purpose; it is not evidence by itself of an effect. The registry lists no statistical analyses for the primary endpoint, and the outcome is not reduced to one comparison because it has several categories or time points. As a result, no conclusion about the direction, size, or statistical significance of the primary comparison can be drawn from the registry record.
The safety data are reported separately for core and long-term follow-up groups. During the core period, serious adverse events affected 0 of 8 participants in the LDE225 group and 1 of 2 in the placebo group. During long-term follow-up, the corresponding counts were 1 of 8 and 0 of 2. These are small group counts, and the periods should not be conflated. The record also reports participants affected by other adverse events, but the counts do not supply a randomized estimate of efficacy. The deaths field is not reported.
Consequently, the registry record supports a description of the trial’s design, endpoint definition, and recorded safety counts, but not an estimate of clinical clearance benefit or a precise comparison of risks. The absence of a reported analysis is not evidence that the groups were the same; it means that the relevant comparison is not reported in the registry record.
9. Statistical Methods Explained
The trial used a randomized, double-blind, parallel-group design. In general, random assignment is intended to reduce systematic differences between treatment groups, while masking can limit the influence of treatment knowledge on participant experiences, clinical assessments, or other study procedures. The registry identifies the trial as randomized and double-blind but does not report the randomization procedure, allocation concealment, or the practical details of masking. The record lists LDE225 and matching placebo as the interventions.
How to interpret the endpoint scale
The primary endpoint is not a single binary event in the record. It is a six-category clinical rating, from worsening through complete clearance, assessed at Day 113. The categories encode an ordering of clinical response, but the distances between adjacent categories are not necessarily equal. In general, analyses of ordered categories can preserve the full response pattern, while a binary analysis requires a chosen threshold and discards some distinctions. The registry does not report which statistical method was planned or used for this endpoint, nor does it identify a threshold for collapsing categories.
A number-of-participants measure can be reported as counts within categories or as a treatment comparison based on those counts. Those presentations answer different questions. Counts describe what was observed; a comparative estimate expresses how the groups differed under a specified statistical model. The registry record does not report the primary endpoint counts, a comparative estimate, a confidence interval, or a p-value. No recalculated comparison is available from the posted endpoint information.
Uncertainty and sample-size planning
In general, a confidence interval represents uncertainty around an estimate under the assumptions of the chosen analysis. It is not a guarantee that the true effect lies within the interval, and its interpretation depends on the design and model. Because no primary endpoint estimate or interval is reported, the precision of an LDE225-versus-placebo comparison cannot be assessed from the registry record.
The trial enrolled 10 participants. A small enrollment generally limits the amount of information available for estimating treatment differences, particularly when an outcome has several categories. This observation concerns precision, not the direction of an effect. The registry record does not report a sample-size justification or a protocol-based target tied to a specified effect. It describes assumptions for a planning illustration: two-sided significance level 0.05, equal allocation, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. Such an illustration is planning information, not observed power, and the registry does not report an endpoint analysis from which to assess an observed treatment effect.
What can and cannot be inferred from the analysis record
The registry lists 0 analyses. That means no statistical analysis results for the primary endpoint are reported in the record; it does not establish that no analyses were performed outside the registry. The statistical analysis plan, model specification, handling of the ordered categories, adjustment variables, and interim-analysis procedures are not reported in the registry record. No assumptions about those choices can therefore be attributed to the trial.
Multiplicity is relevant in general when several outcomes, time points, or comparisons are tested, because multiple testing can increase the chance of at least one apparently unusual result. The record identifies secondary outcomes for histological clearance of main target BCCs and disease burden by BCC tumor counts, in addition to the primary clinical assessment. It does not report a multiplicity strategy, a hierarchy of tests, or results for those outcomes. The primary endpoint description also mentions main target and, as appropriate, secondary target BCCs. The specific handling of multiple lesions within a participant is not reported.
Analysis populations affect the interpretation of estimates because inclusion and exclusion rules determine which participants contribute data. The registry describes a pharmacodynamic analysis set consisting of participants with evaluable or complete pharmacodynamic or biomarker parameter data and without protocol deviations with significant impact on those data. It does not report whether that population was used for the primary clinical clearance analysis, whether all randomized participants were included in that analysis, or how missing endpoint assessments were handled. These details matter because exclusion of participants or incomplete assessments can change the population represented by an estimate.
For adverse-event counts, the registry gives participants at risk and participants affected separately for the core and long-term follow-up groups. Those counts can be read as descriptive safety information. In general, a comparison of event counts should account for the definition of the event, the observation period, and the number of participants contributing information. The record does not provide a comparative safety model or confidence intervals. Serious-event counts from different follow-up periods should not be combined without a prespecified rationale and adequate details about participant overlap and observation time.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary clinical clearance outcome and secondary outcomes for histological clearance of main target BCCs and disease burden by BCC tumor counts. It also reports that the primary assessment uses several response categories. In general, testing multiple outcomes, time points, or contrasts raises multiplicity concerns: the more tests performed, the greater the opportunity for a chance finding. The registry record does not report a prespecified testing hierarchy, multiplicity adjustment, or the statistical plan for these outcomes. It also reports no analyses, so there are no posted endpoint tests to interpret.
Missing-data methods are not reported in the registry record. It does not state how absent Day 113 assessments, withdrawals, or incomplete outcome records were handled, or whether any sensitivity analyses were planned or conducted. Without these details, the effect of missing outcome data on a treatment comparison cannot be evaluated.
The record describes a pharmacodynamic analysis set that included participants with evaluable or complete pharmacodynamic or biomarker data and without protocol deviations that significantly affected those data. It does not say whether this was the population used for the clinical clearance endpoint. An intention-to-treat analysis, a per-protocol analysis, or another primary-endpoint population is not reported in the registry record. The distinction is important because analysis-population rules determine which randomized participants contribute to the estimate and can affect its interpretation.
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 |
|---|---|---|---|
| LDE225 - Core | 0 | 8 | 0.0% |
| Placebo - Core | 1 | 2 | 50.0% |
| LDE225 - Long Term Follow-up | 1 | 8 | 12.5% |
| Placebo - Long Term Follow-up | 0 | 2 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| LDE225 - Core | 7 of 8 |
| Placebo - Core | 1 of 2 |
| LDE225 - Long Term Follow-up | 2 of 8 |
| Placebo - Long Term Follow-up | 0 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | LDE225 - Core | Placebo - Core | LDE225 - Long Term Follow-up | Placebo - Long Term Follow-up |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | 0 of 8 | 0 of 2 | 1 of 8 | 0 of 2 |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 8 | 1 of 2 | 0 of 8 | 0 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | LDE225 - Core | Placebo - Core | LDE225 - Long Term Follow-up | Placebo - Long Term Follow-up |
|---|---|---|---|---|---|
| Muscle spasms | Musculoskeletal and connective tissue disorders | 3 of 8 | 1 of 2 | 0 of 8 | 0 of 2 |
| Nausea | Gastrointestinal disorders | 2 of 8 | 0 of 2 | 0 of 8 | 0 of 2 |
| Fatigue | General disorders | 2 of 8 | 0 of 2 | 0 of 8 | 0 of 2 |
| Nasopharyngitis | Infections and infestations | 2 of 8 | 0 of 2 | 0 of 8 | 0 of 2 |
| Blood creatine phosphokinase increased | Investigations | 2 of 8 | 0 of 2 | 0 of 8 | 0 of 2 |
| Gamma-glutamyltransferase increased | Investigations | 1 of 8 | 0 of 2 | 1 of 8 | 0 of 2 |
| Headache | Nervous system disorders | 2 of 8 | 0 of 2 | 0 of 8 | 0 of 2 |
| Alopecia | Skin and subcutaneous tissue disorders | 2 of 8 | 0 of 2 | 0 of 8 | 0 of 2 |
| Cardiovascular disorder | Cardiac disorders | 1 of 8 | 0 of 2 | 0 of 8 | 0 of 2 |
| Vertigo positional | Ear and labyrinth disorders | 1 of 8 | 0 of 2 | 0 of 8 | 0 of 2 |
Serious events with the highest arm-level rate: basal cell carcinoma (50.0%), cellulitis (12.5%).
The registry separates adverse-event reporting into core and long-term follow-up groups. For serious adverse events during the core period, 0 of 8 participants were affected in the LDE225 group and 1 of 2 in the placebo group. During long-term follow-up, 1 of 8 LDE225 participants and 0 of 2 placebo participants were affected. These are participant counts, not estimates adjusted for differences in follow-up time or other factors.
For other adverse events, the core-period counts were 7 of 8 participants in the LDE225 group and 1 of 2 in the placebo group. In long-term follow-up, the counts were 2 of 8 and 0 of 2, respectively. The periods are reported separately, and the registry does not provide enough information to combine them or to interpret them as rates over a common exposure time.
The registry lists basal cell carcinoma at 50.0% and cellulitis at 12.5% among the top serious adverse-event terms. The record does not specify the denominators or group attribution for those percentages in the registry record, so they should not be assigned to a particular group. Death counts are not reported in the registry record. Given the small at-risk counts, these figures are descriptive and do not by themselves establish a comparative safety profile.
12. What the Result Does, and Does Not, Mean
This registry record establishes that a phase II randomized, double-blind, placebo-controlled study was conducted in adults with NBCCS, with LDE225 given at 400 mg once daily in the listed active regimen. It also specifies a clinical clearance endpoint, its assessment scale, and a Day 113 assessment. These details help define what the investigators intended to measure.
The record does not report the primary endpoint results. It therefore cannot establish how many participants in either group experienced worsening, no change, or degrees of clearance, and it cannot support an estimate of the difference between groups. No confidence interval, p-value, or other endpoint analysis is reported. This lack of posted results should not be interpreted as evidence of no difference; it leaves the treatment comparison unknown from the registry record.
The safety entries describe counts of participants affected by serious and other adverse events in core and long-term follow-up. They do not provide a complete comparative safety analysis, and the death counts are not reported. The small numbers at risk mean that the counts should be treated as descriptive rather than as precise estimates of event probabilities.
The study’s proof-of-concept and exploratory labels describe its stated purpose, not the outcome. In general, preliminary trials can help characterize an intervention and inform the design of later research, but the design label alone does not show that a clinical effect was observed. The registry record also does not report a statistical analysis plan, sample-size justification, or analysis of missing outcome data. Any firm interpretation of efficacy or comparative safety would require results and methods that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a clearly defined endpoint and a reported treatment effect. The registry provides a detailed clinical response scale, including gradations from worsening to complete clearance, but does not report how participants were distributed across those categories. Knowing the endpoint definition is necessary for interpreting results; it cannot substitute for the results themselves.
The small enrollment of 10 also makes the reporting of uncertainty especially important. In general, estimates from small studies may be sensitive to the outcomes of individual participants, and confidence intervals help show how much uncertainty remains. No primary endpoint estimate or confidence interval is reported in the registry record. This limits what can be learned about either the magnitude or precision of a treatment comparison.
The record also illustrates why analysis populations and follow-up periods need clear descriptions. The stated pharmacodynamic analysis set is not explicitly linked to the primary clinical endpoint, while safety counts are separated into core and long-term follow-up. Without a clear endpoint population, missing-data approach, and statistical plan, readers cannot fully reconstruct how a treatment estimate would have been produced.
Finally, the study is labeled exploratory and dose-ranging, while the listed active regimen describes LDE225 at 400 mg once daily. Identifying that distinction prevents assumptions about unlisted dose groups. Overall, the registry supplies useful design and measurement details but does not report the primary comparison needed to evaluate the stated clinical question.
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 trial constrain interpretation of the registry record. Enrollment was 10, and the primary endpoint is a multi-category clinical assessment. The endpoint counts and any comparative estimate are not reported, so neither the observed response distribution nor its precision can be evaluated. The statistical method for handling the ordered categories is also not reported.
The trial is described as dose-ranging, but the listed active regimen is 400 mg once daily. Other dose levels, if any, are not reported in the registry record. The allocation ratio and the methods used to generate and conceal randomization are also not reported. These omissions limit reconstruction of the design from the registry information.
The endpoint was assessed at Day 113, but the record does not report primary outcome results, missing-data handling, or whether the pharmacodynamic analysis population was used for this clinical measure. The statistical analysis plan, sample-size justification, multiplicity strategy, and interim-analysis procedures are not reported. Consequently, it is not possible to assess the prespecified analysis choices or whether the posted outcome reporting reflects them.
Safety counts are divided into core and long-term follow-up, but the registry entries do not specify exposure time or participant overlap between those periods. Death counts are not reported. The listed serious adverse-event terms lack group-specific denominators in the information available for interpretation. These limitations make the safety entries descriptive and prevent a more detailed comparative assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS) — NCT01350115.
- Registry record last updated 2015-10-19; status last verified 2015-09.
- Results first posted 2015-10-19.
- 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
The registry identifies NCT01350115 as a completed phase II, randomized, double-blind, parallel-group proof-of-concept study sponsored by Novartis Pharmaceuticals. It enrolled 10 adults with NBCCS and compared LDE225, listed at 400 mg once daily, with matching placebo. The primary endpoint was clinical clearance of main target BCCs at Day 113, measured on a six-point scale from worsening to complete clearance.
The study description includes a 12-week treatment period, initial follow-up of approximately 6-8 weeks, and long-term follow-up. The registry reports descriptive adverse-event counts for core and long-term follow-up groups. It does not report primary endpoint results, statistical analyses, a statistical analysis plan, or the handling of missing primary outcome data. The record therefore describes the trial’s design and measurement approach but does not provide an efficacy comparison.