An Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Edge): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Edge) (NCT03789656), a na phase 2 study. The primary outcome is Change From Baseline (Median of Screening Values) in Insulin-like Growth Factor-1 (IGF-1) Level.

2. Clinical Question

In practical statistical terms, this is an exploratory question about change over time within a treated group, not a direct estimate of treatment effect relative to an untreated or alternative-treatment group. A within-group change can describe what happened during follow-up, but without a control group it cannot separate changes associated with the study drug from other explanations. The posted registry record also does not provide the primary endpoint estimate, so the direction, size, and precision of the observed change cannot be assessed.

3. Trial Design

ACROBAT Edge is registered as a Phase 2, open-label, exploratory study with a single-group model. The registry lists allocation as not applicable and masking as none. Its stated purpose was to evaluate the safety, pharmacokinetics, and efficacy of paltusotine in participants with acromegaly treated with somatostatin analogue-based regimens. The registry lists 47 enrolled participants.

The record gives the study start as 2019-03-12 and primary completion as 2020-08-03, with status completed. The intervention is paltusotine, formerly called CRN00808. Safety results are organized into dose groups labelled 5 mg, 10 mg, 20 mg, 30 mg, and 40 mg. The registry does not establish that these groups are independent cohorts or randomized arms, and the arm descriptions are blank. They should therefore be read as the recorded dose-group summaries, not as evidence of a controlled dose comparison.

The primary outcome is a change in IGF-1 at 13 Weeks, specified as Week 13/End of Treatment. Its analysis population is the Efficacy Analysis Set: Group 1 participants who received at least one dose of study drug. The record lists two secondary outcomes based on participants’ last IGF-1 measurement relative to the upper limit of normal. It also lists four outcome measures and two analyses, but those counts alone do not reveal the analysis hierarchy or statistical procedures.

There is no parallel control group in this design. Consequently, the study can describe within-group measurements and safety observations, but cannot by design provide a randomized estimate of how outcomes would have differed under another treatment. Details such as the exact dosing schedule, protocol-defined reasons for dose changes, and the statistical analysis plan 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: A total of 45 subjects were planned to be enrolled in the study. 47 subjects participated in the study.

Screening Period: up to 6 Weeks

Treatment Period: up to 13 Weeks

Reasons for not completing this period:

Follow-up Period: up to 4 Weeks

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy Analysis Set includes all subjects in Group 1 who received at least one 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: Of the 47 participants who received CRN00808-03, 42 participants completed the trial, 4 participants withdrew from treatment period, and 1 participant withdrew consent during follow up. No participants withdrew due to adverse events.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline (Median of Screening Values) in Insulin-like Growth Factor-1 (IGF-1) Level, measured over 13 Weeks.

The primary endpoint is change from baseline in IGF-1 level at Week 13/End of Treatment. The record defines baseline using the median of screening values and identifies the endpoint summary as a median with inter-quartile range. The unit is recorded as ng/mL x ULN. The analysis applies to Group 1 participants in the Efficacy Analysis Set, defined as those who received at least one dose of study drug.

IGF-1 is the biomarker named in the trial’s primary question. A change-from-baseline endpoint summarizes how measurements at the end of the stated follow-up differ from the baseline reference. Using a median describes the middle of the observed values and is less sensitive than a mean to unusually high or low measurements. The inter-quartile range describes the spread of the central portion of those values; it does not, by itself, show uncertainty in the estimated median.

In general, a biomarker endpoint can provide a measurable way to summarize biological change over a defined period. It is not automatically equivalent to a patient-important outcome, and interpretation depends on the study context and the size and precision of the estimate. Here, the numerical median change and inter-quartile range are not reported in the registry record. The endpoint definition alone therefore does not establish whether the observed IGF-1 level increased or decreased, or by how much.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median and inter-quartile range show?

The primary outcome is summarized using a median and inter-quartile range. In general, the median is the central value after observations are ordered. It can be useful when a distribution is skewed or includes values far from the centre, because extreme observations have less influence on it than they do on a mean. The inter-quartile range describes the spread of the middle half of the observations. It conveys variability among observed values, but it is not a confidence interval and does not directly quantify how precisely the population median has been estimated.

The endpoint specifies change from a baseline defined as the median of screening values. The registry gives the planned time point as Week 13/End of Treatment and the unit as ng/mL x ULN. The result itself, including the median change and inter-quartile range, is not reported in the registry record. Readers should not infer a value from the endpoint title or from the existence of tables and plots elsewhere on the page.

Why does the single-group design affect interpretation?

In general, a single-group study can describe measurements observed in participants over time, but the change is not a randomized comparison. A control group helps estimate what might have occurred over the same period without the intervention or under a different intervention. Without that comparison, time trends, changes in background care, measurement variation, and other influences cannot be disentangled from the treatment-associated change using the design alone.

Open-label means masking was absent. In general, lack of masking can affect participant experience, reporting, management, or assessment, depending on the outcome and study procedures. The registry does not report enough detail to determine whether or how these possibilities affected this study. They are design considerations, not evidence that a particular bias occurred.

What can a confidence interval and a p-value add?

In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of the statistical method. Its width conveys precision: a narrower interval indicates greater precision than a wider interval, all else equal. A p-value measures how compatible the observed data are with a specified null hypothesis under a model; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. Neither a confidence interval nor a p-value for the primary outcome is reported in the registry record. The endpoint summary of median and inter-quartile range should not be mistaken for either.

How should the safety summaries be read?

The registry separates serious adverse events from other adverse events and presents counts by recorded dose group. In general, counts should be interpreted alongside the number at risk, follow-up duration, exposure, event definitions, and whether participants can appear in more than one group. The record lists different numbers at risk across dose groups but does not explain group overlap, exposure duration, or the detailed event-collection rules. The summaries are therefore descriptive and do not establish comparative risk across doses.

The registry also identifies Headache at 2.3% among the top serious terms. That item is a reported term and percentage; the record does not provide additional context to interpret its timing, duration, relationship to treatment, or severity. The serious-event counts should not be combined with other adverse-event counts unless the underlying definitions and potential overlap are known.

What is the role of the sample-size illustration?

The accompanying sample-size section is described as a planning illustration based on the observed effect, not as the trial’s original design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. It is not observed power. The registry design, by contrast, is single-group, so the illustration’s two-arm framework is hypothetical planning rather than a description of the enrolled study.

In general, such planning calculations estimate the sample size needed to detect a chosen effect under specified assumptions. They do not show the probability that a completed study has demonstrated a treatment effect, and they do not replace the observed estimate and its uncertainty. The registry does not report a sample-size justification for the trial itself. No planning result should be read as a substitute for the absent primary outcome estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary IGF-1 change endpoint and two secondary threshold outcomes: the proportion with a last IGF-1 measurement at or below the upper limit of normal, and the proportion at or below 1.5×ULN. It also records four outcome measures and two analyses. These details identify several reported outcome elements, but they do not explain how the analyses were ordered, whether the secondary outcomes were confirmatory or exploratory, or whether any adjustment for multiple testing was planned.

In general, testing multiple outcomes can increase the chance of obtaining at least one apparently notable result by chance if each is interpreted independently. Multiplicity procedures can address that issue, but the appropriate method depends on the prespecified analysis strategy. The statistical plan and any multiplicity adjustment are not reported in the registry record. The numerical results for the primary and secondary endpoints are also not reported, limiting any assessment of how the outcomes relate to one another.

The primary analysis population is defined as all Group 1 participants who received at least one dose of study drug. This is the registry’s stated Efficacy Analysis Set definition; the record does not provide the number included in that set or the number contributing endpoint measurements. It does not describe how missing screening or Week 13 measurements were handled, whether participants who discontinued were included in any analysis, or whether imputation or sensitivity analyses were used.

Missing-data methods matter because results can depend on who remains observed and on the assumptions used for absent measurements. In general, an analysis using only available measurements describes those observed, while imputation relies on assumptions about unobserved values. The registry record does not report which approach was used. Interim analyses, stopping rules, and a detailed statistical analysis plan are also not reported in the registry record. These omissions prevent a fuller assessment of analysis choices, but do not establish that any particular method was or was not used.

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 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: headache (2.3%).

The safety table presents serious adverse events and other adverse events by dose group, with numbers at risk and numbers affected. For the 5 mg group, 2 participants were at risk and 0 were affected in either category. At 10 mg, 47 were at risk, 0 were affected by serious events, and 23 were affected by other adverse events. At 20 mg, 43 were at risk, 1 was affected by a serious event, and 24 were affected by other adverse events. At 30 mg, 37 were at risk, 0 were affected by serious events, and 15 were affected by other adverse events. At 40 mg, 32 were at risk, 0 were affected by serious events, and 19 were affected by other adverse events. The registry reports 0 deaths in each dose group.

Headache is listed among the top serious terms at 2.3%. These are descriptive summaries, not randomized comparisons. The record does not clarify whether participants could contribute to more than one dose group, nor does it provide the exposure duration or event timing needed to compare rates. Counts should not be treated as evidence that one dose is safer than another. The event details and their clinical context are not reported in the registry record.

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

This study’s primary question concerns change in IGF-1 at Week 13/End of Treatment among participants in a defined treated analysis set. The registry provides the endpoint definition, analysis population, and summary measure, but not the numerical result. As a result, the posted record does not show the direction or size of the primary change, its observed spread, or its precision. The secondary IGF-1 threshold outcomes are defined, but their numerical results are also not reported in the registry record.

The design further limits what the study can establish. It is open-label and single-group, with no randomized control group. In general, a within-group change can document that measurements differed over time, but a treatment effect is a comparison with what would have occurred under another condition. That counterfactual comparison is not available from this registered design. The dose-group safety summaries do not create a controlled comparison because the registry does not establish that dose groups are independent or comparable.

The record does report selected adverse-event counts and identifies Headache at 2.3% among the top serious terms. These data describe the recorded safety summaries, but do not provide the full context needed to characterize event timing, duration, exposure, or comparative risk. They should not be treated as a complete account of all safety evidence.

In general, statistical evidence is best understood by considering the estimate, its uncertainty, the analysis population, missing data, and the design together. Here, several of those elements are not reported in the registry record. The appropriate conclusion is therefore limited: this page can describe what the study set out to measure and the selected safety counts it recorded, but cannot determine from this record whether the primary endpoint changed, how precisely it was estimated, or how outcomes compare with another treatment. These limits concern interpretation of the record, not a clinical recommendation.

13. Why This Trial Matters Statistically

ACROBAT Edge is statistically informative as an example of how a biomarker question is framed in an exploratory, open-label, single-group study. Its primary endpoint specifies both a time point and a summary method: change in IGF-1 at Week 13/End of Treatment, summarized as a median with inter-quartile range. Those choices describe what was to be measured, while also showing why the numerical estimate and its uncertainty are essential for interpretation.

The study also illustrates the difference between observing change and estimating a comparative treatment effect. A single-group design can provide descriptive follow-up information, but it lacks the randomized control needed to distinguish change associated with treatment from other possible influences. This distinction remains important even when an endpoint is objective or quantified: measurement precision does not remove design limitations.

The registry’s separate dose-group safety summaries raise another general issue. Counts reported for groups with different numbers at risk are useful descriptions, but do not automatically support dose-to-dose comparisons. Information about group overlap, exposure, follow-up, and event definitions is needed to interpret such comparisons responsibly. Those details are not reported in the registry record.

Finally, the record shows why outcome definitions, analysis populations, missing-data procedures, and multiplicity plans should be considered together. The Efficacy Analysis Set is defined, but its size and missing-measurement handling are not reported. The primary and secondary endpoints are named, but the results and multiplicity approach are not reported. The statistical value of the record is thus in clarifying the intended question and the limits of the available summaries, rather than in supporting a numerical conclusion about the primary endpoint.

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 record constrain interpretation. The numerical primary IGF-1 change and inter-quartile range are not reported in the registry record. The same is true of the two secondary threshold outcomes. Consequently, the stated endpoints cannot be used to describe observed efficacy results or their precision. The registry lists no comparative control arm, so the design does not provide a randomized estimate against another treatment or placebo.

The study is open-label, and masking is listed as none. The record does not describe outcome-assessment procedures or other safeguards that might affect interpretation. It also does not provide an analysis plan, sample-size justification, missing-data methods, multiplicity procedures, or interim-analysis details. Their absence from the registry record should not be taken as proof that no such procedures existed, but it prevents assessment of them from this record.

The primary efficacy population is defined as Group 1 participants who received at least one dose, but its actual size and endpoint completion are not reported. Dose-group safety counts vary, and the record does not state whether participants could be represented in more than one group or explain exposure duration. It is therefore not possible to interpret dose-group counts as independent cohorts or compare their risks reliably.

Finally, the record gives only selected safety summaries and a top serious term. It does not include the broader event context needed to assess timing, duration, severity, or attribution. These limitations do not invalidate the study; they define what can and cannot be concluded from the registry record as posted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Edge) — NCT03789656.
• Registry record last updated 2025-02-17; status last verified 2025-01.
• Results first posted 2025-02-17.
• 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

ACROBAT Edge (NCT03789656) is registered as a completed Phase 2, open-label, single-group exploratory study of paltusotine in participants with acromegaly receiving somatostatin analogue-based regimens. The registry lists 47 enrolled participants, a study start of 2019-03-12, and primary completion on 2020-08-03.

The primary endpoint is median change in IGF-1 from the median of screening values at Week 13/End of Treatment, with inter-quartile range, among Group 1 participants who received at least one dose. The primary numerical result and secondary outcome results are not reported in the registry record. Safety summaries are listed by dose group, including serious and other adverse-event counts and deaths; they are descriptive and do not establish dose comparisons.

The single-group design, absent masking, and unreported analysis details limit interpretation. The record defines the study question and selected safety results, but does not support a numerical assessment of the primary endpoint or a controlled treatment comparison.