Study to Evaluate the Safety, PK, and Dose Response of Paltusotine in Subjects With Carcinoid Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety, PK, and Dose Response of Paltusotine in Subjects With Carcinoid Syndrome (NCT05361668), a randomized phase 2 study. The primary outcome is Safety - Incidence of Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This was a randomized, phase 2, parallel-group study of paltusotine in subjects with carcinoid syndrome. The registry record marks masking as none, so the study was open-label rather than blinded. The randomized treatment phase was followed by an open-label extension. The primary safety endpoint applies to the randomized treatment phase, described as 8 weeks.

Participants were assigned to 40 mg or 80 mg paltusotine, taken orally each day. The arm descriptions state that dose changes were allowed for symptom control. The primary endpoint description says that results were analyzed according to the initially assigned randomized arm, regardless of actual dose received. This is an assignment-based way of grouping results; it does not mean that every participant necessarily took only the assigned dose throughout treatment.

The registry record reports enrollment of 36 and a completed study. It does not report how enrollment was distributed across the analysis populations beyond the adverse-event figures, which list 18 at risk in each randomized arm. Those figures should not be treated as a complete account of all participant flow, since screening, withdrawal, and extension-phase details are not reported in the registry record.

Randomization is intended, in general, to make treatment groups comparable in expectation, while a parallel-group design assigns participants to a group that is followed alongside the other group. Lack of masking can matter for outcomes involving reporting, clinical decisions, or assessment, although the registry record does not describe any specific effect of open-label conduct on these results. Details of the randomization procedure, allocation concealment, and conduct of the extension are not reported in the registry record.

The listed comparison is between two active paltusotine dose assignments; no placebo or untreated group is listed. The registry record does not report a protocol justification for the selected doses, the planned sample size rationale, or a separate efficacy objective with a reported result. The study purpose includes safety, pharmacokinetics, and exploratory dose response, but the posted outcome information does not provide a dose-response analysis.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set included all randomized participants receiving ≥1 dose. TEAEs (reported per randomized arm) are defined as AEs from first to last dose date (end of RTP, or early term), plus 28 days (Safety follow up). Dose changes at Weeks 2 or 4 were allowed for symptom control (increase) or poor tolerability (decrease). Results are provided by randomized arms (40 mg and 80 mg paltusotine).

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 Safety - Incidence of Treatment-emergent Adverse Events (TEAEs), measured over First dose of investigational medicine to End of Randomized Treatment Phase (8 weeks).

The primary endpoint is safety: the incidence of treatment-emergent adverse events, including serious events and events leading to discontinuation. The description also includes changes from baseline to the end of the randomized treatment phase in clinical laboratory tests, physical examination findings, vital signs, electrocardiograms, and continuous cardiac monitoring. That monitoring is specified only for subjects on a 120 mg dose; whether any participant received that dose is not reported in the registry record. The endpoint description also includes all-cause mortality and says deaths were categorized by primary cause following medical adjudication.

A treatment-emergent adverse event is defined in the record by its timing: an event from the first through the last dose date, including the end of the randomized treatment phase or early termination, plus 28 days for safety follow-up. Events were coded using MedDRA and were to be summarized by treatment group, system organ class, and preferred term.

Safety endpoints are used to describe the occurrence and character of unwanted events during treatment and follow-up. Counts can identify the number of participants recorded as affected, but alone do not establish causation or quantify the comparative risk with precision. The posted results include counts for serious and other adverse events and deaths. The record does not give a complete numerical result for every safety measure named in the endpoint description, such as changes in laboratory values or vital signs.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to treatment groups using a chance-based process. In general, this can reduce systematic differences between groups at baseline, although it cannot guarantee balance in a small study. The record identifies the study as randomized but does not report the sequence-generation method, allocation concealment, or any stratification factors. Those details are not reported in the registry record, so the practical protections used during assignment cannot be assessed from the posted information.

What does the parallel-group design mean?

In a parallel-group study, assigned groups are followed during the same study period rather than participants crossing through every treatment condition. This design supports a comparison between assigned groups, but interpretation depends on how treatment exposure, follow-up, and outcome collection are handled. Here, participants could have dose changes for symptom control, while the endpoint description says outcomes are analyzed by initially assigned arm regardless of actual dose received. This preserves the randomized assignment grouping for the reported arm summaries, but the record does not give participant-level exposure histories.

The study is marked as having no masking. In general, masking means keeping participants, clinicians, or outcome assessors unaware of treatment assignment, where feasible. An open-label design can affect event reporting or clinical management, particularly for outcomes that rely on observation or judgment. The registry record does not describe whether or how these possibilities were addressed. It also does not report an independent blinded event-adjudication process, except that deaths were categorized by primary cause based on medical adjudication.

How should event counts be understood?

The adverse-event results are counts of participants with events, rather than a model-based estimate of treatment effect. Counts are useful for showing how many participants in each assigned arm were recorded as affected. They do not, on their own, account for uncertainty or establish that a difference is unlikely to be due to chance. A confidence interval, when reported, expresses the range of effect estimates compatible with the data under the statistical model; it can convey precision that a count alone cannot. The registry record does not report confidence intervals for the posted adverse-event figures.

For rare or infrequent events, a small change in the number of recorded cases can substantially alter a descriptive comparison. General statistical practice is therefore to avoid treating sparse counts as a stable estimate of the underlying event frequency. Counts may also be affected by duration of exposure and completeness of follow-up. The record defines the safety window as extending from first through last dose, including 28 days of safety follow-up, but does not report individual follow-up time or whether follow-up was complete for every participant.

The listed serious-event terms require careful interpretation. General adverse-event coding can organize clinical events into preferred terms and broader system categories. A participant may experience multiple events, and a term-level list may not represent mutually exclusive people. The registry record does not state whether participants contributed to multiple listed terms, so the percentages for those terms should not be added or interpreted as a participant total.

What can an arm comparison establish?

A randomized comparison can support estimation of differences between assigned groups when an analysis plan, outcome definitions, and uncertainty measures are available. A statistical test would address how compatible the data are with a specified null hypothesis under its assumptions; it would not by itself establish clinical importance or causation. No hypothesis test, effect estimate, confidence interval, or adjusted model is reported for the primary safety figures. The record lists no analyses, so no sponsor analysis can be compared with a simple recalculation from summary statistics.

The planning illustrations are not observed power and are not part of the trial's reported results. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with a detectable effect expressed as a fraction of the observed effect. Such illustrations are hypothetical design calculations; they are not proof that the study had adequate power or that a result is conclusive. No planning values are included in the registry entries, and the trial's own sample-size justification is not reported in the registry record.

Over-dispersion is a general issue for count outcomes: it occurs when observed variability is greater than a model's assumed variability. If present, a simple model can understate uncertainty. The posted primary safety results are participant counts, and no count-model analysis or assessment of over-dispersion is reported. This concept therefore explains a general modeling concern, not a finding about this study.

Finally, assignment-based summaries and exposure-based summaries answer different questions. Grouping by random assignment preserves the original treatment comparison, while grouping by dose actually received can reflect changes made after randomization and may no longer retain the same protection against confounding. The registry record states that results were analyzed by initial assignment; it does not report a separate analysis by actual dose received.

10. Multiplicity, Missing Data and Analysis Populations

The primary safety endpoint contains several components: treatment-emergent adverse events, including serious events and events leading to discontinuation; changes in several safety measures; and mortality. The record also lists pharmacokinetics as a secondary outcome and describes exploratory dose response in the study purpose. When several outcomes or comparisons are examined, multiplicity can increase the chance of at least one apparently notable result occurring by chance. General approaches include prespecifying a primary comparison or adjusting inference across multiple tests. The registry record does not report a multiplicity strategy or a statistical testing hierarchy.

The endpoint description says adverse events were summarized by treatment group, system organ class, and preferred term. It does not report which safety components were formally tested, whether any were considered exploratory, or how interpretation across the components was controlled. The record lists no analyses, so there is no posted inferential result to evaluate for multiplicity handling.

Missing-data procedures are not reported in the registry record. The safety analysis set is described as including randomized participants who received at least one dose, and event timing includes a safety follow-up period. However, the record does not report the number of participants with incomplete follow-up, how missing safety assessments were handled, or whether outcome-specific populations differed from the safety analysis set.

The registry record does not provide a detailed participant-flow account, reasons for discontinuation, or a missing-data sensitivity analysis. For safety outcomes, incomplete observation can matter because participants with shorter follow-up have less time in which events can be recorded. The stated event window clarifies the intended observation period, but it does not establish that all participants completed that period.

These omissions limit assessment of how complete and comparable the observed safety information was between arms. They do not show that missingness or multiplicity problems occurred; they mean the record does not report enough detail to assess those issues.

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: cardiac failure (5.6%), dehydration (5.6%), large intestinal obstruction (5.6%), encephalopathy (5.6%), infections and infestations (5.6%).

The registry record lists serious adverse events for 2 of 18 participants at risk in each randomized arm. It lists other adverse events for 16 of 18 at risk in the 40 mg arm and 15 of 18 at risk in the 80 mg arm. Deaths are listed as 0 in the 40 mg arm and 1 in the 80 mg arm. These are participant counts organized by initial randomized assignment.

Counts describe what was recorded, not whether an event was caused by treatment. The serious-event listings include Cardiac failure, Dehydration, Large intestinal obstruction, Encephalopathy, and Infections and infestations, each reported at 5.6%. The registry record does not specify whether these terms overlap within participants, so the terms and percentages should not be summed or read as separate people.

The figures do not include uncertainty intervals or a formal comparison. The death listing does not give a cause or a treatment-relatedness judgment. Although the endpoint description says deaths were categorized by primary cause following medical adjudication, those details are not reported in the registry record. The results should therefore be read as descriptive safety observations, not as a causal or definitive comparison between doses.

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

The posted information describes safety observations in a randomized phase 2 study of paltusotine in subjects with carcinoid syndrome. It reports serious-event counts, other adverse-event counts, and deaths by initially assigned arm. The serious-event count is 2 in each arm, while the other-event counts and death counts are also available as descriptive figures. These observations indicate what the registry record reports for the stated safety population; they do not provide a complete characterization of every endpoint component.

The results do not show that one dose is safer than the other. A difference in counts, or the absence of a difference in a particular count, is not by itself a statistical demonstration of an effect or equivalence. The record does not report confidence intervals, hypothesis tests, adjusted estimates, or a prespecified threshold for interpreting between-arm differences. It also does not report detailed results for the listed safety parameters or a dose-response analysis.

The figures do not establish whether paltusotine caused any event. A temporal definition identifies events recorded during the treatment and follow-up window, but temporal occurrence is not the same as causal attribution. The posted death count likewise does not identify cause or treatment relationship.

The information also does not establish effectiveness for carcinoid syndrome symptoms. The study purpose mentions exploratory dose response, and the registry lists pharmacokinetics as a secondary outcome, but the outcome results described in the record are safety-focused. No clinical efficacy conclusion can be drawn from these safety counts.

More broadly, the registry record is a limited source for evaluating precision and completeness. It does not report an analysis plan, missing-data methods, detailed participant flow, or an inferential comparison. The appropriate conclusion is therefore descriptive: the record documents the listed events in the two randomized paltusotine arms, while leaving uncertainty about comparative effects and broader clinical implications.

13. Why This Trial Matters Statistically

This trial illustrates how a randomized design can coexist with important limits on what the posted results establish. Assignment to 40 mg or 80 mg paltusotine creates a direct active-dose comparison, and reporting by initially assigned arm retains the assignment-based grouping described in the endpoint definition. At the same time, permitted dose adjustments mean assigned dose and dose actually received are not necessarily identical. The record does not provide enough detail to assess exposure patterns or their relationship to events.

Safety is not a single measurement. The primary endpoint description spans treatment-emergent events, serious events, discontinuations, clinical measurements, and mortality. Each component can provide a different perspective, and a count of participants with events cannot substitute for numerical results on laboratory values, vital signs, or other safety parameters. The record's broad endpoint definition is therefore wider than the subset of safety figures posted.

The study also shows why descriptive counts need uncertainty and context. Counts are easy to interpret at face value, but sparse events and limited sample sizes can leave considerable uncertainty about the underlying pattern. Without an estimate and interval or a reported statistical comparison, readers cannot quantify how precisely the arms differ. A matching serious-event count is not proof of equivalent safety, just as a difference in another count is not proof of a dose effect.

Finally, the record distinguishes the randomized treatment phase from the open-label extension, while the listed primary safety timeframe concerns the randomized phase. Keeping those periods separate is important when interpreting which observations belong to the primary endpoint. The registry's limited posted analysis details make transparent reporting of populations, follow-up, and uncertainty especially important for understanding the scope of these findings.

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 posted safety results are descriptive, and the registry record lists no analyses. There are no reported effect estimates, confidence intervals, or formal comparisons for the primary safety figures. Consequently, the precision of between-arm differences cannot be assessed from the record, and the counts should not be treated as evidence of either a dose effect or equivalence.

The endpoint includes more than the adverse-event counts available in the posted results. It also names discontinuation due to adverse events, changes in laboratory tests, physical examination findings, vital signs, electrocardiograms, continuous cardiac monitoring, and mortality categorization. Numerical findings for those components are not reported in the registry record. The monitoring description mentions a 120 mg dose, but whether any participant received that dose is not reported.

Adverse-event term listings do not provide enough information to determine participant overlap, event recurrence, severity beyond the serious classification, or causal relationship to treatment. The death listing does not state cause or treatment-relatedness. The registry record does not give the numbers with incomplete follow-up, detailed reasons for discontinuation, or missing-data handling.

The record reports dose changes were permitted and that results were analyzed according to initial randomized assignment, regardless of actual dose received. It does not report how often dose changes occurred or the doses participants actually received. This limits interpretation of the relationship between assigned arm and exposure.

Details of the randomization process, sample-size justification, statistical plan, multiplicity handling, and analysis populations beyond the stated safety set are not reported in the registry record. The study purpose includes exploratory dose response, but a dose-response result is not posted. These limitations concern what can be evaluated from the registry information; they do not establish that unreported procedures or analyses were not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety, PK, and Dose Response of Paltusotine in Subjects With Carcinoid Syndrome — NCT05361668.
• Registry record last updated 2026-03-19; status last verified 2026-03.
• Results first posted 2025-10-31.
• 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

NCT05361668 is a completed phase 2 randomized, open-label, parallel-group study of paltusotine in subjects with carcinoid syndrome. The randomized treatment phase compared initial assignment to daily oral 40 mg or 80 mg paltusotine for 8 weeks and was followed by an open-label extension. Enrollment was 36.

The primary endpoint concerns safety, including treatment-emergent adverse events and changes in safety parameters. The posted adverse-event figures list serious events in 2 participants in each arm, other adverse events in 16 participants in the 40 mg arm and 15 in the 80 mg arm, and deaths of 0 and 1, respectively. The record lists no analyses, and does not report inferential comparisons, confidence intervals, or a dose-response result.

These data support a descriptive account of the posted safety observations, not a causal or definitive comparison of doses. Details of missing-data handling, multiplicity, and the trial's statistical plan are not reported in the registry record.