This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate Cortisol Reserve in Response to Adrenocorticotropic Hormone (ACTH) Stimulation Test Following Baxdrostat Treatment Compared to Placebo in Participants With Uncontrolled Hypertension (NCT06336356), a randomized phase 2 study. The primary outcome is Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT06336356 |
| Phase | Phase 2 |
| Condition | Uncontrolled Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 48 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
Participants with uncontrolled hypertension. The registry record reports enrollment of 48 participants and defines the full analysis set as randomized participants who received at least one dose of study intervention.
Intervention
Baxdrostat 2 mg as an oral tablet once daily. The study evaluated cortisol measures after 8 weeks of treatment.
Comparator
Placebo tablet once daily, in a randomized, double-blind, parallel-group study.
Primary question
How do serum cortisol levels before and after ACTH stimulation at Week 8 characterize cortisol response following baxdrostat treatment compared with placebo? The overall study purpose describes assessment of serum free cortisol response; the listed primary endpoint describes serum total cortisol measurements.
The endpoint focuses on cortisol response to a stimulation test rather than blood-pressure change. ACTH is used to stimulate cortisol production, and measurements before and after stimulation allow the response to be characterized. The record specifies a 250 μg ACTH test at baseline and Week 8, with cortisol measured before and after stimulation. Its stated definition of normal stimulated cortisol is at least 18 μg/dL at 60 minutes (±10 minutes) after stimulation.
The registry record does not report numerical primary endpoint results or a treatment comparison. It also does not report a numerical result for the listed secondary outcomes. Consequently, the clinical question can be described from the study design and endpoint definitions, but the posted record does not establish how the groups differed in cortisol response.
3. Trial Design
This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group study. The registry record describes 48 participants with uncontrolled hypertension. Participants in one arm received baxdrostat 2 mg orally once daily; participants in the other arm received placebo once daily. The official study title specifies 8 weeks of treatment, and the primary endpoint timeframe is Week 8.
The record gives a study start date of 2024-06-10 and a primary completion date of 2024-12-04, and lists the study status as completed. These dates describe the registry record; they do not supply outcome results. The record identifies AstraZeneca as sponsor.
The primary endpoint is described as the number of participants with serum total cortisol measurements before and after ACTH stimulation. The test used 250 μg ACTH at baseline and Week 8, with serum cortisol assessed before and after stimulation. The record also lists incidence of abnormal stimulated cortisol at Week 8 and the number of participants with adverse events and adverse events of special interest as secondary outcomes.
The full analysis set is defined as randomized participants who received at least one dose of study intervention. The registry record does not report further details about randomization procedures, allocation concealment, stratification, or the precise analysis population used for each endpoint. It lists no outcome analyses. Thus, the design can be described, but the record does not support a detailed account of how the primary comparison was performed.
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: Participants who met all the inclusion and none of the exclusion criteria were enrolled in this study. All study assessments were performed as per the schedule of assessment.
Overall Study
| Stage | Baxdrostat 2 mg | Placebo |
|---|---|---|
| STARTED | 32 | 16 |
| COMPLETED | 30 | 16 |
| NOT COMPLETED | 2 | 0 |
Reasons for not completing this period:
| Reason | Baxdrostat 2 mg | Placebo |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Lost to Follow Up | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The full analysis set included all randomized participants who received at least one dose of study intervention. Here, 'number of participants analyzed' and 'number analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
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 full analysis set included all randomized participants who received at least one dose of study intervention.
| Characteristic | Unit | Baxdrostat 2 mg | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 32 | 16 | 48 | |
| Age, Continuous | Years | 64.1 (SD 9.2) | 66.1 (SD 7.4) | 64.8 (SD 8.6) |
| Sex: Female, Male: Female | Participants | 17 | 9 | 26 |
| Sex: Female, Male: Male | Participants | 15 | 7 | 22 |
| Race/Ethnicity, Customized: Black or African American | Participants | 12 | 7 | 19 |
| Race/Ethnicity, Customized: White | Participants | 20 | 9 | 29 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Serum Total Cortisol Level Before and After Adrenocorticotropic Hormone (ACTH) Stimulation Test, measured over Week 8.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint concerns serum total cortisol levels measured before and after ACTH stimulation. The record describes measurements at baseline and Week 8, with Week 8 identified as the endpoint timeframe. It says the primary endpoint is each participant’s cortisol level at each timepoint and that the number of participants with normal stimulated serum total cortisol at baseline is presented. This wording leaves some ambiguity about which timepoint-specific count the endpoint title represents; the registry record does not resolve that ambiguity with numerical results.
The test used 250 μg ACTH. A stimulated result is defined as normal when cortisol is at least 18 μg/dL at 60 minutes (±10 minutes) after stimulation. If the Week 8 result is abnormal, a repeat test is conducted. For that repeat, abnormality requires both a level less than 14.8 μg/dL at 30 minutes (± 5 minutes) and less than 18 μg/dL at 60 minutes (±10 minutes).
General explanation: a stimulation test assesses whether an organ responds to a stimulus. Measuring cortisol before and after ACTH provides a way to characterize the cortisol response under the study’s stated threshold. This is a physiological endpoint; it is not itself a measure of blood-pressure control. The registry record does not report the observed cortisol counts or an estimated difference between treatment groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the study as completed but lists no analyses for the primary outcome. It gives endpoint definitions and the analysis population, but it does not report the number of participants meeting the cortisol thresholds, group-specific cortisol results, an estimated treatment contrast, or a confidence interval. The primary outcome therefore cannot be interpreted as evidence of a difference or similarity between baxdrostat and placebo from this record.
The primary outcome includes measurements at multiple timepoints and categories. The registry record indicates that this outcome was not reduced to one comparison. That matters because a count at one timepoint, a change across timepoints, and a threshold-based classification are different summaries of the data. Without the reported estimates and a defined comparison, it is not possible to determine which summary would answer the study question or how precisely it was estimated.
The posted adverse-event figures show zero serious adverse events in the baxdrostat 2 mg group, among 32 participants at risk, and zero in the placebo group, among 16 participants at risk. The record also lists six participants with other adverse events in each group and zero deaths in both groups. These are counts, not estimates of a treatment effect. They do not show event types, timing, severity beyond the serious-versus-other grouping, or whether participants had more than one event.
Zero recorded serious adverse events in these groups should be read as an absence of reported events in the registry figures, not as proof that serious events cannot occur. Counts from a study of this enrollment provide limited information about uncommon outcomes. The record lists no serious adverse-event terms, and it does not provide event-level descriptions for the other adverse events in the information available.
Overall, the registry record supports a description of the study question, design, endpoint thresholds, and the listed adverse-event counts. It does not provide the primary outcome results needed to judge the magnitude or precision of any cortisol difference. The completed status alone does not fill that gap: completion describes study status, not the presence of posted analyses.
9. Statistical Methods Explained
What the endpoint counts. The primary outcome is described in terms of participant cortisol measurements before and after ACTH stimulation, with normality assessed against a stated threshold. The registry record says the primary endpoint is each participant’s cortisol level at each timepoint and identifies counts of participants with normal stimulated serum total cortisol at baseline. A threshold-based count reduces a continuous laboratory measurement to categories such as normal or abnormal. That can make the result easier to interpret against a predefined criterion, but it also discards information about how far an individual value lies from the threshold. The record does not provide the underlying individual measurements or group counts.
What a group comparison would mean. General explanation: a treatment comparison asks whether an outcome differs between groups, while also describing the uncertainty in the estimate. For a continuous measure, a comparison may concern average values or change; for a categorical outcome, it may concern the proportion meeting a classification. The appropriate summary depends on the prespecified endpoint and analysis plan. The registry record does not report a specific primary comparison or an estimate with a confidence interval, so no such effect size can be interpreted for this study.
Confidence intervals and precision. General explanation: a confidence interval gives a range of values compatible with the observed data under a stated statistical procedure. A narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. It does not replace the point estimate, and it does not by itself resolve clinical relevance. No primary endpoint confidence interval is reported in the registry record. Without a point estimate and interval, the precision of the cortisol comparison cannot be assessed.
Thresholds and repeat testing. The record defines normal stimulated cortisol as at least 18 μg/dL at 60 minutes (±10 minutes). For an abnormal Week 8 result, it specifies a repeat test and requires both the less-than 14.8 μg/dL level at 30 minutes (± 5 minutes) and less-than 18 μg/dL level at 60 minutes (±10 minutes) for the repeat result to be considered abnormal. These rules define how a result is classified; they are not outcome findings. The registry record does not report how many repeat tests were conducted or how repeat-test data were incorporated into any analysis.
Repeated measurements and categories. General explanation: measurements from the same participant across time are related, rather than independent observations. An analysis that compares repeated measurements should account for that relationship. Similarly, when an outcome has multiple categories or timepoints, the choice of a single summary can affect the question answered. The registry record indicates that the primary outcome has several categories or timepoints and was not reduced to one comparison. It does not describe a model or test for handling the repeated measurements.
Over-dispersion and count outcomes. General explanation: for some count data, observed variability can exceed what a simple statistical model expects; this is called over-dispersion. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. The posted adverse-event figures are participant counts, but the record does not report a statistical model for them or enough detail to assess over-dispersion. The primary outcome is also described as participant counts, but no inferential analysis is listed.
Planning assumptions. The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; it says the effect to detect is a stated fraction of the observed effect. These are assumptions for an illustrative planning calculation, not a report of the trial’s original design rationale. The registry record does not report the observed effect used for that illustration or a corresponding required number of participants per arm. Such planning values, when available, are not observed power and do not establish the probability that the completed study detected an effect.
What is not available. The registry record lists zero analyses and does not give a statistical test, model, adjustment strategy, or primary treatment-effect estimate. It also does not report a sample-size justification, interim analysis plan, or details of how results were handled if participants had missing measurements. Without these elements and the numerical endpoint results, the statistical evidence for the primary question cannot be evaluated from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint involves multiple cortisol categories or timepoints, and the registry record indicates it was not reduced to one comparison. The record lists additional outcomes: incidence of abnormal stimulated cortisol at Week 8 and the number of participants with adverse events and adverse events of special interest. When several outcomes, timepoints, or comparisons are examined, the chance of obtaining an apparently notable result by chance can increase. General explanation: multiplicity procedures can control or describe that issue, but the appropriate approach depends on the analysis plan and the questions designated as primary or secondary. Any multiplicity adjustment or hierarchy of hypotheses is not reported in the registry record.
The record defines the full analysis set as all randomized participants who received at least one dose of study intervention. It does not report how many participants were included in the primary endpoint analysis at each timepoint, whether anyone was excluded from a specific analysis, or how missing cortisol measurements were handled. It also does not report imputation methods, sensitivity analyses, or assumptions about missingness. These omissions prevent assessment of whether missing data could have affected the result, even if outcome estimates were available.
The registry record lists no outcome analyses. It does not identify a per-protocol population or describe whether an intention-to-treat analysis was conducted. The full analysis set definition is the only stated analysis-population definition for the primary outcome. A completed study status and an enrollment count do not establish that every enrolled participant contributed data to every endpoint.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Baxdrostat 2 mg | 0 | 32 | 0.0% |
| Placebo | 0 | 16 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Baxdrostat 2 mg | 0 of 32 |
| Placebo | 0 of 16 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Baxdrostat 2 mg | 6 of 32 |
| Placebo | 6 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Baxdrostat 2 mg | Placebo |
|---|---|---|---|
| Dizziness | Nervous system disorders | 2 of 32 | 1 of 16 |
| Headache | Nervous system disorders | 1 of 32 | 2 of 16 |
| Lethargy | Nervous system disorders | 1 of 32 | 1 of 16 |
| Hypotension | Vascular disorders | 1 of 32 | 1 of 16 |
| Nausea | Gastrointestinal disorders | 2 of 32 | 0 of 16 |
| Vomiting | Gastrointestinal disorders | 2 of 32 | 0 of 16 |
| Nasopharyngitis | Infections and infestations | 0 of 32 | 1 of 16 |
| Seasonal allergy | Immune system disorders | 0 of 32 | 1 of 16 |
| Vision blurred | Eye disorders | 0 of 32 | 1 of 16 |
| Arthropod bite | Injury, poisoning and procedural complications | 0 of 32 | 1 of 16 |
The serious adverse-event counts are zero for baxdrostat 2 mg, with 32 participants at risk, and zero for placebo, with 16 participants at risk. The registry record also lists zero deaths in each group. These figures are counts of participants, not a statistical comparison, and no confidence interval or test for the difference is reported.
The record lists six participants with other adverse events in each group. It does not provide the specific event terms in this summary, the number of events per participant, or additional detail about duration or severity. No serious adverse-event terms are listed. The registry record names adverse events of special interest as a secondary outcome, but it does not provide a separate numerical result for that outcome in the available information.
General explanation: a zero count in a study does not establish that the underlying risk is zero. Safety counts should be read alongside their denominators and the period of observation; they are descriptive and may be imprecise, particularly for uncommon events. The record’s counts describe what was reported for the study groups and should not be treated as proof of safety or as a comparison demonstrating equal risk.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized, double-blind comparison designed to characterize cortisol response after ACTH stimulation following 8 weeks of baxdrostat or placebo. It specifies the test procedure, thresholds for normal and abnormal results, the full analysis set definition, and adverse-event counts. It does not report numerical results for the primary cortisol endpoint or a treatment-effect estimate.
As a result, the posted record does not show whether cortisol measurements differed between groups, how large any difference was, or how precise an estimate might be. It also does not establish that the groups had equivalent results: absence of a reported comparison is not evidence of no difference. The endpoint description and the study’s completed status cannot substitute for results.
The listed serious adverse-event counts are zero in both groups, with zero deaths; the listed other adverse-event count is six participants in each group. These figures are descriptive, and the record does not give enough detail to evaluate event types or make a broad safety comparison. The counts do not answer the primary cortisol question.
The study concerns participants with uncontrolled hypertension, but the primary endpoint is cortisol response to ACTH stimulation, not a reported blood-pressure outcome. The record therefore cannot be used to infer an effect on blood pressure from the information presented. Nor does it provide evidence for outcomes beyond the specific study population, treatment schedule, and endpoints described. The sound interpretation is limited to the design and descriptive data that the registry record reports, while recognizing that the central primary outcome findings are absent.
13. Why This Trial Matters Statistically
This study is statistically notable because its central question concerns a physiological response measured repeatedly and classified using explicit thresholds. The distinction between a measured cortisol value and a normal-or-abnormal classification matters: a threshold count can communicate whether participants crossed a specified criterion, while continuous measurements preserve information about the size of the response. The registry record describes both pre- and post-stimulation measurements, but does not report numerical results that would allow either form of evidence to be assessed.
The design includes a placebo comparison and double masking, which are relevant features when interpreting differences between groups. However, design features do not establish what the data show. Without an endpoint estimate, uncertainty interval, or specified analysis, readers cannot judge the magnitude or precision of any group contrast. This illustrates why registry design details and posted outcome analyses answer different questions.
The record also makes the limits of descriptive safety counts clear. Zero serious adverse events and six participants with other adverse events in each group are useful descriptions of the posted counts, but they are not a substitute for comparative analysis or detailed event reporting. Counts can be especially limited when the outcome is uncommon.
Finally, the stated planning illustration is distinct from observed findings. Planning assumptions can illustrate how a target effect and statistical approach relate to a proposed sample size, but the registry record does not report the inputs or resulting participant counts for that illustration. No planning calculation can be read as observed power or as evidence that the study did or did not detect a cortisol difference.
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 principal limitation for interpretation is that the registry record lists no outcome analyses and does not provide numerical results for the primary cortisol endpoint. It gives the endpoint definition and thresholds, but no participant counts by group for the primary result, no treatment-effect estimate, and no confidence interval. This prevents assessment of effect magnitude and precision.
The endpoint description refers to baseline normal stimulated cortisol counts while the listed timeframe is Week 8, and it also describes measurements at baseline and Week 8. The record does not clarify this wording with a specific reported analysis. It is therefore not possible to identify a single numerical primary comparison from the registry record.
The study enrolled 48 participants, and the listed safety denominators are 32 for baxdrostat 2 mg and 16 for placebo. Those counts describe the posted safety information but do not by themselves establish the allocation procedure or the analysis population for each outcome. The registry record does not report the number analyzed for the primary endpoint at each timepoint, missing-data handling, or reasons for any unavailable measurements.
The record does not report the statistical model, hypothesis-testing procedure, multiplicity handling, sample-size justification, or interim analyses. It also does not provide detailed adverse-event terms beyond the serious-event summary and the count for other adverse events. These limitations are specific to the information reported for this study and restrict both the efficacy interpretation and the depth of safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate Cortisol Reserve in Response to Adrenocorticotropic Hormone (ACTH) Stimulation Test Following Baxdrostat Treatment Compared to Placebo in Participants With Uncontrolled Hypertension — NCT06336356.
- Registry record last updated 2025-12-17; status last verified 2025-12.
- Results first posted 2025-12-17.
- 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.
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18. Record Summary
The registry record describes NCT06336356 as a completed Phase 2, randomized, double-blind, placebo-controlled, parallel-group study sponsored by AstraZeneca. It enrolled 48 participants with uncontrolled hypertension. The study compared baxdrostat 2 mg orally once daily with placebo for 8 weeks.
The primary endpoint concerns serum total cortisol before and after ACTH stimulation, with the test performed at baseline and Week 8 using 250 μg ACTH. The registry record defines normal stimulated cortisol as at least 18 μg/dL at 60 minutes (±10 minutes) and gives additional criteria for repeat testing after an abnormal Week 8 result. The full analysis set includes randomized participants who received at least one dose of study intervention.
No primary outcome analyses or numerical primary results are listed. The posted safety counts show zero serious adverse events and zero deaths in both groups, and six participants with other adverse events in each group. The record does not provide a primary treatment-effect estimate or detailed analyses of the listed outcomes.