Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease (NCT01915303), a na phase 2 study. The primary outcome is Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35.

2. Clinical Question

3. Trial Design

This was a prospective, multicenter, open-label phase II study of pasireotide alone or in combination with cabergoline in patients with Cushing’s disease. The registry record describes a single-group model, with allocation listed as not applicable and masking listed as none. Enrollment was 68. The study status is terminated. The record lists a start date of 2014-03-06 and a primary completion date of 2016-09-05; it does not report why the study was terminated.

The intervention is described as pasireotide with or without cabergoline, and the arm description says pasireotide alone or with cabergoline. This wording identifies treatment regimens but does not document a randomized assignment process or a control group. It is therefore not appropriate to interpret differences between regimens as treatment effects from a like-for-like comparison based on this record. The allocation field is not applicable, and the record explicitly cautions that the arms are not a like-for-like control comparison.

The primary endpoint was the percentage of responders with mUFC at or below 1.0 times ULN collected or imputed at Week 35. The primary endpoint population is named as the full analysis set. Other listed outcomes include urinary free cortisol at scheduled visits, responder definitions that combine the threshold with a reduction from baseline, duration of response, ACTH, serum cortisol, and sitting blood pressure. The record lists 22 outcome measures, but it does not provide outcome estimates in the information available for this analysis.

The registry record does not report a detailed statistical analysis plan, treatment allocation procedures, or a sample-size justification. The record contains no analysis entries. These omissions limit what can be concluded about the prespecified statistical approach and the basis for the study’s enrollment target.

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.

Core Phase

Reasons for not completing this period:

Extension Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full 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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35, measured over Baseline up to week 35.

The primary endpoint measured the percentage of participants whose mean urinary free cortisol (mUFC) was at or below 1.0 times the upper limit of normal (ULN) at Week 35, using an observed or imputed assessment. In general, a responder endpoint turns a continuous measurement into a classification: each participant is counted according to whether the measurement meets the stated threshold. The resulting percentage communicates how common that classification was in the analysis population, rather than showing the full spread of cortisol measurements.

The endpoint description specifies how baseline and follow-up mUFC were obtained. Baseline was based on the average of three screening-period 24-hour urinary free cortisol samples. Follow-up mean 24h-UFC was determined from two 24-hour urine collections on consecutive days before the visit. These repeated collections are intended to characterize urinary cortisol using more than a single collection, as described in the registry record.

The endpoint is clinically interpretable as a threshold-based biochemical response measure, but it compresses information. Participants just above and well above the cutoff are both classified as nonresponders under this definition, while participants meeting the cutoff are grouped together. Other listed outcomes include continuous mUFC measurements and an alternative responder definition that also considers a reduction from baseline. Considering such outcomes can provide complementary descriptions, but their results are not reported in the registry record.

The record specifies a 95% confidence interval for the primary percentage, but does not report the percentage or its interval. Consequently, the observed response frequency and the precision of its estimate cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial results often combine an estimate of an outcome with a measure of its uncertainty. For a percentage endpoint, the estimate describes the proportion of participants classified as responders in the analysis population. A confidence interval gives a range of values compatible with the data under the statistical procedure used. In general, it helps readers judge precision; it is not a guarantee that the true value lies within the interval. The registry record identifies a 95% confidence interval for the primary endpoint, but does not report the interval or the response estimate. Therefore neither the result nor its precision can be assessed.

What does the responder percentage represent?

The endpoint is a binary classification based on mUFC at Week 35: a participant either meets the stated threshold, at or below 1.0 times ULN, or does not. The reported percentage would summarize the frequency of meeting that criterion in the full analysis set. In general, binary outcomes are straightforward to communicate, but the classification loses information about the distance between a participant’s measurement and the threshold. Continuous mUFC results can help retain information about the distribution and change in measurements. The registry record lists continuous mUFC outcomes, but their estimates are not reported in the information available for this analysis.

How should an interval estimate be read?

A confidence interval describes uncertainty around an estimate, conditional on the data and the method used to calculate it. It does not account automatically for every source of uncertainty, such as study design limitations, missing data, or outcome selection. For a percentage, the interval’s width is affected by the observed response frequency and the amount of usable data, among other factors. Since the registry record does not include the endpoint percentage, interval limits, or endpoint-specific observed denominator, these features cannot be examined. The enrollment figure should not be treated as the number contributing an observed Week 35 measurement.

What does open-label, single-group design imply?

In general, an open-label design means treatment masking is absent, while a single-group design does not provide a randomized concurrent control group in the study model described. These features do not make an outcome unusable, but they constrain the interpretation of comparisons. A change from baseline may reflect the intervention, the course of the condition, other care, measurement variation, or other influences. Without a suitable control comparison, the separate contribution of these influences cannot be isolated from the registry description. The record also identifies pasireotide alone or with cabergoline, but explicitly cautions that the listed arms are not a like-for-like control comparison.

Why does over-dispersion matter generally?

For binary outcomes, a simple statistical model may assume that participants’ outcomes vary independently and that a common response probability describes the group. In general, over-dispersion means the observed variability is greater than that model expects. If it is not addressed when present, uncertainty estimates can be too small, making results appear more precise than warranted. This is a general statistical consideration, not a reported feature of this study. The registry record does not describe a model for over-dispersion, clustering, or other departures from standard assumptions.

What can be inferred from the planning illustration?

The record describes sample-size calculations as planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such illustrations are prospective planning quantities under their assumptions; they are not observed power and do not show the probability that the study detected an effect after the fact. The illustration’s assumptions do not establish that the original trial was designed with those methods. The registry record does not report the trial’s own sample-size justification, and no calculated participant counts are reported in the information available for this analysis.

For time-to-event calculations, the record says the total number of events is reported, while other sample-size illustrations give participants per arm. This distinction matters in general because event-driven planning depends on the number of outcome events rather than simply the number enrolled. These planning descriptions do not provide observed trial results and should not be conflated with the primary responder endpoint.

Finally, the endpoint description specifies an imputation procedure. For participants who completed the end-of-treatment visit at Week 35 but lacked an mUFC evaluation, the last available mUFC assessment at or after the previous visit before the final week was carried forward as the last-week assessment. This is a form of last-observation-carried-forward imputation. In general, it substitutes an earlier observed value for a missing later value, relying on an assumption that the earlier value is a suitable stand-in. The record does not report how many endpoint values were imputed or the results of analyses using alternative missing-data assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 22 outcome measures, including the primary responder endpoint, other mUFC measures and definitions, duration of response, hormone measurements, and blood pressure outcomes. When a study examines multiple outcomes or multiple comparisons, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can help control that risk, but they may also affect precision or the interpretation of individual tests. The registry record does not report whether a multiplicity adjustment was planned or applied, nor does it describe a hierarchy among the listed outcomes.

The primary endpoint population is identified as the full analysis set. The record does not provide a detailed definition of that set, the number included in the primary endpoint analysis, or participant flow through the study. Enrollment was 68, but enrollment is not necessarily the same as the number with an observed or imputed endpoint assessment.

The endpoint description includes a specific imputation rule for participants who completed the Week 35 end-of-treatment visit but lacked an mUFC evaluation: the last available assessment at or after the previous visit before the last week was carried forward. The registry record does not state how many participants were affected, why measurements were missing, or whether other missing-data methods were used for participants outside that description. It also does not report sensitivity analyses assessing how alternative assumptions could change the result.

The record contains no analysis entries. It does not report an analysis plan, handling of protocol deviations, interim analyses, or the inferential procedures used. These are not evidence that particular methods were or were not used; they are details not reported in the registry record. As a result, the effect of missing-data choices and multiplicity on any efficacy conclusion cannot be evaluated from this record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (2.9%), cholelithiasis (2.9%), anaemia (1.5%), coronary artery disease (1.5%), glucocorticoid deficiency (1.5%).

For the registry group labelled All Patients, serious adverse events were reported for 15 of 68 participants at risk. Other adverse events were reported for 67 of 68 participants at risk, and deaths were reported for 3 participants. These figures describe the counts recorded for the study group; they do not by themselves establish that an event was caused by treatment. The registry record does not provide the causal attribution or further context needed to interpret each event.

The most frequently listed serious adverse event terms include abdominal pain and cholelithiasis, each reported as 2.9%. Anaemia, coronary artery disease, glucocorticoid deficiency, and intra-abdominal haematoma are each listed as 1.5%. These are the registry’s reported percentages for the terms; they should not be read as a comparative risk against an untreated or randomized control group, which is not described in this single-group record.

Serious adverse events are a defined subset of safety outcomes and should not be conflated with all adverse events. A participant may experience an event that is not classified as serious, and the listed serious-event terms do not constitute a complete description of every event or its timing. The registry record does not report event-level narratives, exposure-adjusted rates, or whether the deaths were considered related to treatment. Safety interpretation should therefore remain descriptive and limited to the reported counts and terms.

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

The registry record establishes that a prospective, multicenter, open-label phase II study evaluated pasireotide alone or with cabergoline in patients with Cushing’s disease. It defines a primary biochemical response endpoint at Week 35, based on whether mUFC was at or below 1.0 times ULN. It also describes the baseline collection approach, the follow-up collection approach, and a carry-forward rule for a particular category of missing Week 35 assessments. These details clarify what the primary outcome was intended to represent.

However, the primary endpoint’s observed response percentage and 95% confidence interval are not reported in the registry record. The endpoint definition cannot substitute for its result. The information available therefore does not establish how frequently participants met the threshold, how precise that percentage was, or how the result compared with another treatment. The same limitation applies to the other listed efficacy outcomes: their titles are present, but their estimates are not reported.

The study’s single-group, open-label design also limits comparative interpretation. The record does not describe randomized allocation or a like-for-like control group, and it cautions that the intervention arms are not a like-for-like control comparison. A measured outcome in this study would describe participants in the study context; without an appropriate control comparison, it would not isolate what would have happened under another treatment or no study intervention.

The reported adverse-event counts and terms provide descriptive safety information for the registry group. They do not establish whether any event or death was caused by treatment, and the registry record does not report such attribution. Nor do the reported figures provide a controlled comparison of safety.

In short, this record supports conclusions about the study’s design, endpoint definition, and listed safety data. It does not support a quantitative conclusion about primary efficacy, a comparative treatment effect, or treatment causality for the reported adverse events. Those distinctions are important when reading a registry entry whose outcome methods are described but whose primary result is not reported.

13. Why This Trial Matters Statistically

This study is statistically notable because its primary endpoint is a threshold-based percentage, yet the registry record does not report the corresponding estimate or confidence interval. That gap illustrates an important distinction between specifying an outcome and reporting its result. A clearly defined endpoint helps identify the scientific question, but readers also need the estimate, its uncertainty, and the analysis population to judge what the study observed.

The endpoint combines repeated urine measurements into a mean and then classifies participants according to a ULN threshold. This makes explicit how the biochemical response was defined, while also highlighting the trade-off inherent in dichotomizing a continuous measure. A responder percentage can be easy to interpret, but it does not show how far measurements were from the threshold or the shape of the underlying distribution. The record’s list of continuous mUFC outcomes suggests complementary descriptions were considered, although their results are not reported.

The imputation rule is another statistically important feature. Carrying forward an earlier assessment can permit a Week 35 classification when that visit’s mUFC evaluation is missing, but it relies on assumptions about the relevance of that earlier value. The record does not report the number of imputed assessments or sensitivity analyses, so the influence of this choice cannot be evaluated.

Finally, the single-group, open-label structure shapes what statistical comparisons can mean. Pasireotide alone and with cabergoline are not documented as randomized, like-for-like control groups. Even a numerical difference between regimens would need cautious interpretation and could not by itself establish a causal contrast. This makes design and reporting context essential: a percentage and interval, if available, would characterize the endpoint estimate, but would not remove limitations in comparative inference.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the primary endpoint percentage or its 95% confidence interval. It also does not report estimates for the other listed efficacy outcomes. This prevents assessment of the observed response, its precision, or consistency across outcomes. Enrollment was 68, but the record does not provide the endpoint-specific analysis denominator or participant flow, so the number contributing an observed or imputed Week 35 result cannot be determined from this information.

The study is described as open-label and single-group, with allocation listed as not applicable. The record cautions that the pasireotide-alone and pasireotide-with-cabergoline arms are not a like-for-like control comparison. It does not report how treatment regimen was selected or allocated. Consequently, the registry description does not support a controlled comparison of the regimens or attribution of an outcome to cabergoline’s addition.

The primary endpoint uses a threshold and a specified carry-forward rule for a subset of missing Week 35 measurements. The record does not report the number of missing measurements, the reasons for missingness, the number imputed, or sensitivity analyses. It also does not define the full analysis set in detail. These omissions make it difficult to assess how missingness or analysis-population choices might affect the result.

The registry lists 22 outcome measures but does not report a multiplicity approach or detailed statistical analysis plan. It contains no analysis entries and does not report interim analyses, the trial’s sample-size justification, or the reason for termination. The termination status and completion date are recorded, but the reason for termination is not reported in the registry record. These limitations concern what is documented; they do not establish which methods may have been used outside the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease — NCT01915303.
• Registry record last updated 2020-09-18; status last verified 2020-08.
• Results first posted 2020-09-18.
• 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

NCT01915303 is a phase II, prospective, multicenter, open-label study of pasireotide alone or in combination with cabergoline in patients with Cushing’s disease. The registry describes a single-group model, lists allocation as not applicable, and records enrollment of 68. The study status is terminated; the reason for termination is not reported in the registry record.

The primary endpoint was the percentage of responders whose mUFC was at or below 1.0 times ULN at Week 35, collected or imputed, in the full analysis set. The endpoint estimate and 95% confidence interval are not reported in the registry record. The entry lists 22 outcome measures and includes descriptive safety counts: serious adverse events for 15 of 68 at risk, other adverse events for 67 of 68 at risk, and 3 deaths. The record does not report causal attribution for those safety outcomes.