Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 (Crinecerfont) in Pediatric Participants With Congenital Adrenal Hyperplasia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 (Crinecerfont) in Pediatric Participants With Congenital Adrenal Hyperplasia (NCT04045145), a na phase 2 study. The primary outcome is Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (Morning Window Average).

2. Clinical Question

In general, a pharmacodynamic endpoint tracks a biological measurement in relation to treatment exposure. It can help characterize whether a treatment is associated with a change in a measured biological parameter over the study period. It is distinct from a patient-centered clinical outcome: the registry’s primary endpoint is a laboratory concentration, not a reported measure of symptoms, functioning, or longer-term health. The record lists additional Day 14 percentage-change outcomes for 17-OHP over a 24-hour period, ACTH, androstenedione, and testosterone. No comparative treatment effect can be estimated from this single-group design because no separate control group is described.

3. Trial Design

This was a Phase 2, open-label, multiple-dose, single-group study of crinecerfont. The registry record lists eight participants as enrolled and the study status as completed. Participants were 14 to 17 years of age and had a documented diagnosis of classic 21-hydroxylase deficiency CAH. The listed intervention was crinecerfont 50 milligrams by mouth twice daily for 14 consecutive days.

There was no randomized allocation and no masking. The registry identifies the allocation as not applicable and the model as single group. Consequently, the study does not provide a randomized treatment-versus-control comparison. Its primary endpoint instead uses measurements from the same participants at baseline and Day 14. Such a before-and-after contrast can describe change over the observation period, but by itself cannot distinguish a treatment-associated change from other influences on measurements over time.

The primary endpoint was a pharmacodynamic measure: percent change from baseline to Day 14 in the morning-window average serum 17-OHP concentration. Samples were collected between 0700 hours and 1000 hours at baseline and after 14 days of dosing. The two samples collected during each morning window were averaged for the endpoint calculation. The registry describes the primary summary as the median and inter-quartile range.

The record lists four secondary outcomes: percent change in 17-OHP over a 24-hour period, and percent change in morning-window averages of ACTH, androstenedione, and testosterone. The sponsor was Neurocrine Biosciences. The study began on 2019-12-12, reached primary completion on 2021-07-02, and is listed as completed. The registry record does not report a concurrent comparator, a masking procedure, or a sample-size justification.

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: Pharmacodynamic (PD) analysis set included all enrolled participants who received at least one dose of study drug and had at least one PD parameter measurement at baseline and at least one PD parameter measurement at the Day 14 visit.

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: All participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline to Day 14 in Serum 17-OHP Concentrations (Morning Window Average), measured over Baseline, Day 14.

The primary endpoint is the percent change from baseline to Day 14 in serum 17-OHP concentration, using the morning-window average. The endpoint description specifies collection between 0700 hours and 1000 hours at both visits. Two samples collected in that window at each visit were averaged before determining the percent change. The stated time frame is baseline and Day 14.

Using a morning window and averaging the two samples collected at each visit defines how the concentration summary was formed. In general, repeated measurements within a defined window can make an endpoint less dependent on a single sample, although the registry does not state a rationale for choosing this procedure. Percent change expresses a follow-up measurement relative to its baseline value; it is not the same as an absolute change in concentration.

The registry identifies the median as the summary measure and the inter-quartile range as its dispersion measure. In general, the median describes the middle of a set of observations, while the inter-quartile range describes the spread of the central half. These summaries can be useful when participant-level changes are unevenly distributed or affected by extreme values. The registry record does not report the median percent change or inter-quartile range, so the magnitude, direction, and variability of the primary endpoint cannot be described from the posted results.

17-OHP is the measured biological parameter in this pharmacodynamic endpoint. The registry also lists other hormone-related pharmacodynamic outcomes, but those do not replace the primary endpoint. The endpoint is a laboratory measure over a short treatment period; its result alone would not establish a change in symptoms or longer-term clinical outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is a single-group, before-and-after study. Each participant’s baseline measurement serves as a reference for that participant’s Day 14 measurement. In general, this approach can describe observed change over time, but it does not create the same counterfactual comparison as a concurrent control group. A randomized control group can help separate treatment effects from changes that might occur for other reasons; no such group is described in this record. The single-group design is therefore important context for interpreting any reported change.

What does the median describe?

The registry specifies the median percent change as the primary summary. In general, the median is the central value after observations are ordered. It is less affected by very high or very low observations than the arithmetic mean. For a small group, the median can be a concise description, but it does not show the full pattern of participant-level responses. Different distributions can share the same median, so the median should be read alongside a measure of spread and, when available, individual observations.

What does the inter-quartile range add?

The inter-quartile range describes the interval spanning the central half of observations. In general, it gives information about variability around the median without requiring the observations to follow a normal distribution. A narrow interval indicates that the central observations are closer together than a wide interval would; neither interval alone shows the full range or the number of participants changing in each direction. The record names the inter-quartile range but does not report its value for the primary endpoint.

How should the endpoint be understood?

The primary measure is a percent change in a concentration from baseline to Day 14. In general, a relative change expresses the follow-up value in relation to the baseline value, whereas an absolute change reports the difference in the measurement’s original units. Relative and absolute changes answer different descriptive questions. The registry lists the endpoint unit as percent change and specifies the measurement procedure: two morning-window samples were averaged at each visit, with the morning window defined as 0700 hours to 1000 hours. The record does not provide the resulting endpoint value or the underlying participant-level measurements.

The endpoint is pharmacodynamic: it concerns a measured biological response during the dosing period. Pharmacokinetics, also named in the study objectives, concerns how drug concentrations change over time. The registry record does not provide pharmacokinetic results in the registry record described for this analysis. Nor does the primary endpoint directly measure symptoms, daily functioning, or longer-term clinical outcomes. General interpretation should keep these different kinds of outcomes distinct.

What can uncertainty measures tell readers?

In general, a confidence interval is a range of values compatible with an estimate under a specified statistical procedure. It conveys uncertainty in an estimate, rather than the range of individual participant outcomes. A p-value, when reported, measures how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions; it does not measure the probability that a treatment effect is true. The registry record does not report a confidence interval or p-value for the primary endpoint, and it does not describe the inferential procedure used. Therefore, statistical uncertainty cannot be reconstructed from the median and inter-quartile range alone without additional information.

With a small enrolled group, estimates may be sensitive to the values contributed by individual participants. This is a general consideration, not a calculated precision estimate for this study. The record does not report a formal precision target, a sample-size justification, or enough endpoint results to quantify uncertainty. The eight enrolled participants also should not automatically be treated as eight analyzed participants, because the primary analysis set required dosing and measurements at both specified visits.

The record includes a general planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are illustration assumptions, not evidence that this trial used a two-arm design: the actual study is single-group. The record does not give the illustrated sample-size values in the registry record, and no sample-size justification for the trial is reported in the registry record. Such planning values, when presented, are not observed power and do not establish the probability that the study detected an effect.

General statistical caution also applies to multiple outcomes. Testing several endpoints can increase the chance of at least one apparently unusual result if no approach to multiplicity is specified. The record identifies the primary and secondary outcome measures but does not report a multiplicity procedure or an inferential analysis plan. It is therefore not possible to determine how any statistical tests were selected or interpreted. The registry lists zero analyses, so the outcome descriptions should not be mistaken for numerical analysis results.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome and four secondary outcomes, for five outcome measures in total. The primary measure is the percent change from baseline to Day 14 in morning-window average serum 17-OHP. The secondary measures concern 17-OHP over a 24-hour period and morning-window averages of ACTH, androstenedione, and testosterone. The record lists zero analyses, and does not report numerical results for these measures in the registry record.

In general, examining multiple outcomes raises questions about which findings were designated as primary and whether statistical testing was adjusted to account for multiple comparisons. The outcome list distinguishes a primary measure from secondary measures, but the registry record does not report a multiplicity adjustment or a statistical analysis plan. It is therefore not possible to assess how the study’s investigators intended to control the interpretation of multiple tests, if tests were conducted.

The primary analysis population is defined as enrolled participants who received at least one dose and had at least one pharmacodynamic measurement at baseline and at least one at the Day 14 visit. The record does not report how many participants met these criteria. It also does not report the amount or pattern of missing endpoint data, how missing measurements were handled, or whether any imputation method was used. The enrolled count of eight should not be treated as the confirmed primary-analysis denominator.

The registry record does not report interim analyses, a prespecified statistical analysis plan, or a sample-size justification. Those matters should not be inferred from the endpoint descriptions or from general planning assumptions. Without reported analysis details and endpoint results, the available record supports description of the intended outcomes and analysis population definition, but not a full appraisal of multiplicity control, missing-data methods, or inferential procedures.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists eight participants at risk in the crinecerfont 50 mg group. Zero participants were reported with a serious adverse event, and zero deaths were reported. Six participants were reported with other adverse events. These are participant counts; the record does not provide event terms for the other adverse events in the registry record.

In general, a count of participants with at least one event is not necessarily a count of all events, because one participant may experience more than one event. The reported count also does not indicate whether an event was judged related to treatment. No serious adverse event terms are listed. The absence of reported serious events in this group should be read as a description of the observed study record, not as evidence that serious events cannot occur.

The study had no concurrent control group, so these safety counts do not support a comparative estimate against another treatment or against no treatment. The record describes a 14-day dosing period and eight participants at risk; it does not establish safety over longer periods or in populations beyond the study’s specified participants. The figures are descriptive and do not, on their own, establish causation.

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

This study provides a record of a Phase 2, open-label evaluation of crinecerfont in eight pediatric participants with classic 21-hydroxylase deficiency CAH. The planned treatment was oral dosing twice daily for 14 consecutive days. The primary outcome was a pharmacodynamic measurement of percent change in morning-window average serum 17-OHP from baseline to Day 14. The registry record also describes secondary hormone-related outcomes and reports safety counts.

The record does not report the numerical primary endpoint result. It therefore cannot establish the size or direction of the median change, the spread of participant-level changes, or the precision of an estimate. It also does not provide numerical results for the listed secondary outcomes in the registry record. The endpoint definitions describe what was measured, not what the measurements showed.

Even if a before-and-after change were reported, the single-group design would limit causal interpretation. Without a concurrent comparator, a change across the study period cannot be separated from other influences on measurements. The open-label design and short dosing period are additional context for interpreting the study, but the record does not quantify their influence.

The safety counts show zero participants with a reported serious adverse event, six with other adverse events, and zero deaths among eight at risk. These counts are descriptive; they do not identify causation or permit comparison with another group. They should not be generalized beyond the participants and observation period recorded.

Overall, the registry entry establishes the study’s stated aims, design, endpoint definitions, analysis-population criteria, and reported safety counts. It does not supply the primary efficacy or pharmacodynamic result needed to characterize the observed endpoint change. The available information therefore supports understanding what the study set out to measure and the limits of its design, but not a conclusion about the magnitude of a treatment effect or its clinical implications.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a single-group pharmacodynamic study differs from a randomized comparison. Measurements at baseline and Day 14 can describe within-participant change, but the design does not include a concurrent group to distinguish treatment-associated change from other changes over time. That distinction is central to interpreting results from open-label, single-group studies.

The primary endpoint also illustrates the importance of understanding how an outcome is constructed. The registry specifies a morning collection window, averaging two samples at each visit, and summarizing percent change using the median and inter-quartile range. Those details define the measurement and summary approach. They do not, on their own, provide the observed effect or its uncertainty; the registry record does not report the primary result.

The analysis-population definition is another important statistical feature. Enrollment is listed as eight, while primary endpoint inclusion requires dosing and measurements at both baseline and Day 14. Because the number meeting those requirements is not reported, the enrolled count cannot be assumed to equal the endpoint denominator. Transparent reporting of analyzed numbers and missing-data handling is necessary for readers to understand how much information supports an estimate.

Finally, the record lists multiple outcomes but no analyses, and it does not report a statistical analysis plan, multiplicity procedure, or sample-size justification. These omissions limit assessment of precision and inferential choices. The study remains useful for examining endpoint definitions and design constraints, while its posted results do not permit a numerical interpretation of the primary pharmacodynamic change.

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 enrollment of eight participants limits the amount of information available for describing variation across participants. The record does not report the number who met the primary analysis-set criteria, so the endpoint denominator is uncertain. It also does not report participant-level measurements, missing-data counts, or methods for handling missing observations.

The single-group, open-label design has no concurrent control group and no masking. A baseline-to-Day 14 comparison can describe change over that period, but it cannot isolate a treatment effect from other influences on the measurements. The record does not report a statistical analysis plan, inferential methods, confidence intervals, p-values, or multiplicity procedures.

The planned dosing period was 14 consecutive days, and the primary endpoint was measured at Day 14. The record therefore does not provide evidence about outcomes over longer follow-up. The population was limited to pediatric participants aged 14 to 17 years with documented classic 21-hydroxylase deficiency CAH; the record does not establish how results would apply to other ages or populations.

Most importantly, the registry record does not report the numerical primary endpoint result or results for the listed secondary outcomes in the registry record. The serious adverse event count and other adverse event count are descriptive and have no comparator. These limitations prevent assessment of the endpoint’s observed magnitude, precision, comparative effect, and longer-term meaning.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 (Crinecerfont) in Pediatric Participants With Congenital Adrenal Hyperplasia — NCT04045145.
• Registry record last updated 2024-07-18; status last verified 2024-07.
• Results first posted 2024-07-18.
• 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

The registry record describes a completed Phase 2, open-label, multiple-dose, single-group study of crinecerfont in pediatric participants aged 14 to 17 years with classic 21-hydroxylase deficiency CAH. Eight participants were enrolled. The listed regimen was oral crinecerfont 50 milligrams twice daily for 14 consecutive days.

The primary endpoint was percent change from baseline to Day 14 in morning-window average serum 17-OHP, summarized by the median and inter-quartile range. The record defines the pharmacodynamic analysis population but does not report its size or the primary endpoint result. Four secondary outcome measures are listed, and zero analyses are listed.

The safety record reports zero participants with serious adverse events, six with other adverse events, and zero deaths among eight at risk. No concurrent comparator is described. The record does not report a sample-size justification, statistical analysis plan, multiplicity procedure, or missing-data method.