Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome (NCT01104415), a randomized phase 2 study. The primary outcome is Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase.

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label, multi-center, serial ascending-dose, dose-finding study of telotristat etiprate in participants with symptomatic carcinoid syndrome. The stated purpose was to evaluate safety and tolerability. The registry lists the study as completed, with enrollment of 15 participants. The study start and primary completion dates are 2010-06-15 and 2014-02-12.

The described regimen began with a 2-week run-in period. In the core phase, participants received 150 mg orally three times daily for 14 days. The record describes serial escalations to 250 mg, 350 mg, and 500 mg every 14 days, but the maximum dose description is incomplete. During the open-label extension, participants received their highest tolerated dose, listed as 250 mg or 500 mg, three times daily for 124 weeks. The record says participants who tolerated neither dose were discontinued and completed a 2-week follow-up visit.

The record labels allocation as randomized but the model as single group. It describes telotristat etiprate and does not identify a separate comparator in the primary outcome information. The purpose or implementation of randomization is not reported in the registry record. Masking is listed as none, consistent with the open-label description; additional details about blinding procedures are not reported.

The listed primary outcome is a count of participants with treatment-emergent adverse events and drug-related treatment-emergent adverse events in the core phase. The registry also lists secondary outcomes covering bowel movements, stool form, urgency, nausea, global symptom assessment, abdominal pain or discomfort, flushing episodes, and clinically meaningful symptom reduction. These outcome descriptions do not, by themselves, establish that results were reported or analyzed. The number of outcome measures is listed as 11, while the number of analyses is listed as 0.

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 Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety set (SS) included all the enrolled participants who received at least 1 dose of study drug.

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.

Population: The safety set included all the enrolled participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase, measured over Baseline up to Week 12 in the Core Phase.

The primary endpoint counts participants who experienced any treatment-emergent adverse event and participants who experienced drug-related treatment-emergent adverse events during the core phase. A treatment-emergent adverse event was defined as an adverse event reported after the first treatment dose on Day 1. The record defines an adverse event as an untoward medical occurrence associated with drug use in humans, whether or not it was considered drug-related.

This endpoint is used to describe safety and tolerability during exposure. Counting participants with an event gives a direct summary of how many people in the safety set experienced at least one event of the specified type. It does not describe the number of separate event episodes, the event duration, or the severity of every event. Those details would require additional outcome information.

The endpoint timeframe is baseline up to Week 12 in the core phase. The safety set is defined as enrolled participants who received at least 1 dose of study drug. The adverse-event results list 15 participants at risk in the core phase, with 15 participants recorded as having other adverse events and 3 as having serious adverse events. A separate numerical result for drug-related treatment-emergent adverse events is not reported in the registry record.

Because the record describes a single-group model and does not report a comparator analysis, the endpoint supports descriptive safety reporting rather than a randomized comparison. It cannot establish how event counts would differ under another treatment or under no study treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a count endpoint: the number of participants with specified adverse events. For this kind of outcome, the count is meaningful only alongside the population being counted and the period in which events were collected. The record defines the safety set as enrolled participants who received at least 1 dose of study drug, and gives separate at-risk counts for the core phase and extension period. Keeping those denominators attached to their respective periods is important when reading the results.

What does a participant count capture?

A count of participants with an event answers whether people experienced at least one event in the period. It does not necessarily count every occurrence. If a participant experiences the same type of event more than once, a participant count and an event count can differ. The registry's primary outcome is phrased as a count of participants, so its unit is people with an event, not total event episodes. The record does not report episode counts for the primary outcome.

The distinction between any adverse event and a serious adverse event also matters. These are separate classifications, and the record reports both for the study periods. A serious adverse event count is not a severity score for all adverse events, nor does it indicate that every other adverse event was mild. Detailed severity grades and event-level descriptions are not reported in the registry record.

How should event attribution be understood?

The record defines an adverse event without requiring that it be considered related to the drug. It defines treatment-emergent events by their timing: they were reported after the first dose on Day 1. These definitions establish a way to classify and collect events, but timing alone does not establish causation. Drug-related events form a narrower category according to investigator or sponsor assessment, but the numerical result for that category is not reported in the registry record.

In general, an estimate of the proportion of participants with an event can be accompanied by a confidence interval. A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the method used; it is not a guarantee that the true value lies within the interval. For a small safety set, estimates can be imprecise, and an interval may communicate that uncertainty better than a count alone. No confidence intervals for the adverse-event counts are reported in the registry record. No interval method is identified.

What can an unadjusted comparison tell us?

In general, a comparison between treatment groups requires outcome information for each group and a defined contrast. It may also require methods that account for the allocation design, baseline factors, exposure time, or repeated observations, depending on the question. The record labels allocation as randomized, but lists a single-group model and does not report a comparator analysis for the primary outcome. The adverse-event counts therefore do not support a between-group estimate or a claim about relative risk.

Counts can still describe what was recorded in each study period. But a direct comparison of the core and extension counts would need additional context, including who entered the extension, how long each participant was observed, and whether exposure and event ascertainment were comparable. Those details are not reported in the registry record. The extension period also has a different stated duration from the core outcome timeframe, so the raw counts alone do not adjust for time at risk.

What is the role of significance tests and sample-size planning?

A significance test evaluates data against a specified statistical model and null hypothesis. A p-value, when reported, describes how compatible the data are with that model under the null; it does not measure the size or clinical importance of an effect. No primary-outcome analysis or p-value is reported in the registry record. The count data should not be treated as evidence of statistical significance or its absence.

In general, sample-size calculations use assumptions about the outcome, allocation, significance level, power, and effect to be detected. The registry's planning assumptions describe an illustration based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The assumptions are described as planning illustrations, not as the trial's own design. Such illustrations are hypothetical planning quantities, not observed power and not evidence that the trial was adequately sized. The record does not report a sample-size justification for the study's design.

Where events are rare or counts vary more than a simple statistical model expects, general methods may need to account for over-dispersion or use models suited to sparse data. Over-dispersion means that observed variability exceeds what a chosen model assumes; ignoring it can make uncertainty appear too small. The registry record does not identify a model for the adverse-event counts, and it reports no inferential analysis. These are general considerations rather than claims about methods used in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary safety outcome and secondary measures concerning bowel movements, stool form, urgency, nausea, global symptom assessment, abdominal pain or discomfort, flushing episodes, and symptom reduction. When several outcomes are assessed, the chance of at least one apparently notable result can increase if each is tested separately. Statistical approaches may address this through a prespecified hierarchy, adjustment, or clearly designated exploratory analyses. The analysis plan for multiplicity is not reported in the registry record.

The record lists 0 analyses. Consequently, no analysis set, model, adjustment strategy, or inferential result for the listed outcomes is reported. The presence of an outcome description should not be taken as evidence that it was analyzed or that a result was available. The registry does not report whether the secondary outcomes were intended as confirmatory or exploratory, or whether any outcomes were changed after study initiation.

Missing-data handling is also not reported in the registry record. It does not state how missed visits, incomplete diaries, withdrawal, or unavailable assessments were handled for the secondary symptom outcomes. For safety reporting, the record defines the safety set as enrolled participants who received at least 1 dose, but does not describe how incomplete safety follow-up was managed. Missingness can affect interpretation if the probability of having an observed outcome is related to a participant's condition, treatment exposure, or experience of adverse events.

The participant flow from the core phase into the extension, the reasons for any non-entry or discontinuation, and the extent of missing outcome data are not reported in the registry record. Without those details, the completeness and comparability of period-specific results cannot be assessed. The reported counts remain useful as descriptive registry entries, but they do not resolve these analysis and follow-up questions.

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: therapeutic embolisation (18.2%), upper limb fracture (9.1%), epilepsy (9.1%), cardiac operation (9.1%), inguinal hernia repair (9.1%).

For the core phase, the registry lists 15 participants at risk, 15 with other adverse events, 3 with serious adverse events, and 0 deaths. For the extension period, it lists 11 participants at risk, 11 with other adverse events, 7 with serious adverse events, and 1 death. These are period-specific counts and should be read with their corresponding at-risk groups, not combined into a single study-wide estimate.

The listed serious-event terms are Therapeutic embolisation at 18.2%, and Upper limb fracture, Epilepsy, Cardiac operation, Inguinal hernia repair, and Carcinoid syndrome at 9.1% each. The registry record does not explain the denominator or whether the percentages refer to participants or event episodes. It also does not establish that these events were caused by study treatment. A listed term indicates a reported serious event category, not a causal assessment.

The extension period had a stated duration of 124 weeks, whereas the primary safety endpoint covers the core phase up to Week 12. Raw counts across periods are therefore not a substitute for an exposure-adjusted comparison. The registry record does not report event timing, person-time, detailed severity, or a formal comparison of safety between periods. The death count is reported for the extension, but its cause and relationship to treatment are not reported in the registry record.

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

The results describe adverse events recorded during a single-group, open-label study of telotristat etiprate. They show that adverse events were recorded in the core and extension periods, including serious adverse events and a death during the extension period. These observations are relevant to the study's stated safety and tolerability purpose, but counts alone provide only a limited description of the experience of participants in the study.

The data do not establish that telotristat etiprate caused any particular event. The primary definition includes adverse events whether or not considered drug-related, and the separate numerical count for drug-related treatment-emergent events is not reported in the registry record. The serious-event term listings likewise do not provide a causal assessment. The registry does not report a comparator outcome for the primary safety question, so the counts cannot show how safety differed relative to another treatment or to no treatment.

The record also does not report an analysis of the symptom outcomes listed as secondary measures. Their presence in the registry does not establish that symptoms improved or worsened. No estimate of a treatment effect, confidence interval, p-value, or clinically interpretable comparison for those outcomes is reported in the registry record. The safety counts should not be used as a substitute for efficacy results.

Nor do these findings establish how the results would apply beyond participants in this study. Eligibility details, participant characteristics, and the reasons for entering or not entering the extension are not reported in the registry record. The study description and counts can inform a reader about the recorded trial experience, but they do not answer comparative effectiveness questions, establish causation, or provide a complete account of uncertainty.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registry labels allocation as randomized while listing the model as single group. Those design descriptors answer different questions: randomization concerns how participants are assigned, while a single-group model indicates that the reported design does not present treatment groups for a conventional comparison. The record does not explain how randomization was used. This makes it especially important to avoid interpreting the event counts as a randomized treatment contrast.

The study also illustrates why denominators and observation periods matter in safety reporting. The core phase and extension period have separate at-risk counts, and the extension has a longer stated treatment duration. Counts from those periods describe the recorded events in their respective settings; they do not by themselves account for different exposure time or participant flow. A careful statistical reading retains each count's period and denominator and avoids combining them.

Another important distinction is between an event occurring after treatment begins and an event caused by treatment. The registry defines treatment-emergent events by timing and describes drug-related events as a separate category. Without a reported drug-related count or comparator analysis, causal interpretation is limited. The record's lack of reported analyses also demonstrates that outcome definitions and outcome listings are not equivalent to analyzed results.

Finally, this record highlights the value of reporting analysis plans, missing-data handling, uncertainty intervals, and participant flow. Such details help readers judge precision and possible sources of bias. Their absence does not make the descriptive counts meaningless, but it limits the questions those counts can answer. The central statistical lesson is to distinguish observed event summaries from comparative evidence and from claims about causality.

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 has important limitations for statistical interpretation. It lists randomized allocation but a single-group model, without describing how randomization was applied or identifying a comparator for the primary safety outcome. This leaves the design's comparative structure unclear. The registry reports 0 analyses, so no inferential estimate or formal comparison is available for the listed outcomes.

The adverse-event information is limited to counts by period and listed serious-event terms. Separate counts for drug-related treatment-emergent adverse events, confidence intervals, event timing, detailed severity, and an exposure-adjusted safety analysis are not reported in the registry record. The denominator and calculation used for the serious-event term percentages are also not explained. The record does not report the cause of the death or its relationship to treatment.

Follow-up and participant flow are insufficiently described for assessing the extension results. The record does not report how many participants were eligible for or entered the extension, the reasons for discontinuation, or how long each participant contributed safety information. Although the extension is described as lasting 124 weeks, individual exposure duration and completeness of follow-up are not reported.

The statistical plan is also not reported in the registry record. This includes sample-size justification, missing-data methods, multiplicity handling, and any prespecified model or interim analysis. The symptom outcomes are listed, but analyzed results for them are not reported. Participant characteristics and further eligibility details are likewise not reported, limiting assessment of how representative the study population may be. These gaps constrain precision, causal interpretation, and generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome — NCT01104415.
• Registry record last updated 2019-03-15; status last verified 2019-02.
• Results first posted 2018-04-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT01104415 is a completed Phase 2, open-label study of telotristat etiprate in symptomatic carcinoid syndrome. The registry lists 15 enrolled participants, randomized allocation, and a single-group model. The study description includes a serial dose-escalation core phase followed by an open-label extension at the highest tolerated dose.

The primary outcome counts participants with treatment-emergent and drug-related treatment-emergent adverse events in the core phase up to Week 12. The record lists adverse-event counts for the core and extension periods, but no primary-outcome analysis; the number of analyses is listed as 0. Separate numerical results for drug-related events are not reported in the registry record.

The registry lists symptom-related secondary outcomes, but does not report their analyses. Comparative interpretation is limited by the single-group model, lack of a reported primary-outcome comparator, and absence of analysis, missing-data, and participant-flow details. The results are descriptive safety information and do not establish causation or a comparative treatment effect.