Efficacy and Safety Evaluation of Baxdrostat in Adults with Primary Aldosteronism: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the effect of **baxdrostat** versus placebo on seated systolic blood pressure (SBP) at Week 8 in adult participants with **primary aldosteronism**. This is clinically relevant as primary aldosteronism is characterized by excessive aldosterone secretion, leading to hypertension and increased cardiovascular risk. Effective management of SBP in these patients is crucial for reducing such risks.

Secondary objectives include:

• Assessing the effect of baxdrostat versus placebo on seated SBP after 8 weeks of randomized withdrawal.
• Evaluating the effect of baxdrostat on the percent change in plasma renin activity (PRA) after 8 weeks of randomized withdrawal.
• Determining the effect of baxdrostat versus placebo on achieving serum potassium levels ≥ 3.7 mmol/L without potassium supplementation at Week 8 in participants with baseline serum potassium < 3.7 mmol/L or those receiving potassium supplementation.
• Assessing the effect of baxdrostat versus placebo on the percent change from baseline in PRA at Week 8.
• Evaluating the effect of baxdrostat versus placebo on achieving 24-hour urine aldosterone levels < 10 µg at Week 8 in participants with baseline levels ≥ 10 µg.
• Assessing the effect of baxdrostat versus placebo on 24-hour urine albumin at Week 8.

The clinical trial involves a total of **131 participants** diagnosed with **Primary Aldosteronism**, characterized by excess aldosterone secretion. The study population includes both male and female participants aged 18 years and older. Participants were selected based on specific inclusion criteria, including a documented diagnosis of Primary Aldosteronism as per the 2016 or 2025 Endocrine Society Guidelines, an estimated glomerular filtration rate (eGFR) of at least 45 mL/min/1.73m², and a serum potassium level between 3.0 and 5.0 mmol/L at screening. Additionally, participants must have a stable regimen of antihypertensive medications for at least four weeks prior to randomization and a mean seated systolic blood pressure (SBP) of at least 135 mmHg. The trial does not include vulnerable populations, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled, parallel-group study** to evaluate the efficacy and safety of **Baxdrostat** in adult participants diagnosed with **primary aldosteronism**. The trial aims to assess the effect of Baxdrostat compared to placebo on seated systolic blood pressure (SBP) at Week 8, among other endpoints. The study will involve participants who are 18 years or older, with a documented diagnosis of primary aldosteronism as per the 2016 or 2025 Endocrine Society Guidelines. Participants must have an estimated glomerular filtration rate (eGFR) of at least 45 mL/min/1.73m² and a serum potassium level between 3.0 and 5.0 mmol/L at screening. They should also have a stable regimen of antihypertensive medications for at least four weeks prior to randomization and a mean seated SBP of at least 135 mmHg.

The trial is expected to commence recruitment on August 7, 2025, and conclude by February 18, 2028. The overall duration of the trial is estimated to be approximately 52 weeks, with the maximum treatment period for participants being 52 weeks. Participants will be involved in the study from the screening visit through to the end-of-study visit, with the possibility of early termination if they do not meet the inclusion criteria or if adverse events occur that necessitate withdrawal. The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy outcomes, and a final end-of-study visit to assess the overall impact of the treatment.

Participants will be randomly assigned to receive either Baxdrostat or a placebo, administered orally in tablet form. The study will ensure blinding of both participants and investigators to the treatment allocation to maintain the integrity of the trial results. The primary endpoints include changes in seated SBP from baseline at Week 8, while secondary endpoints will evaluate additional parameters such as changes in plasma renin activity (PRA) and serum potassium levels. The trial is categorized as a Phase III study, indicating its focus on confirming the therapeutic efficacy and monitoring adverse reactions in a larger participant population.

The clinical trial involves the administration of **Baxdrostat**, a synthetic molecule developed by AstraZeneca AB, in tablet form. Baxdrostat is an experimental medication being evaluated for its efficacy and safety in adult participants with **Primary Aldosteronism**. The active substance, baxdrostat, is of chemical origin. The trial includes two different dosing regimens of Baxdrostat. The first regimen involves a maximum daily dose of 2 mg, with a total maximum dose of 728 mg over a treatment period of 52 weeks. The second regimen allows for a maximum daily dose of 4 mg, with a total maximum dose of 1400 mg over a 50-week treatment period. Both regimens are administered orally.

In addition to the experimental medication, the study employs a **placebo** control, referred to as Baxdrostat Placebo. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know who is receiving the active medication or the placebo. The placebo is designed to mimic the appearance of the Baxdrostat tablets but contains no active substance. The administration route and frequency for the placebo match those of the Baxdrostat tablets to ensure consistency in the study protocol.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. This monitoring is crucial for maintaining the integrity of the trial results and for accurately assessing the efficacy and safety of Baxdrostat compared to the placebo. The trial's primary objective is to evaluate the effect of Baxdrostat on seated systolic blood pressure (SBP) at Week 8, as well as other efficacy endpoints.

The efficacy of Baxdrostat in the treatment of **Primary Aldosteronism** will be assessed through a randomized, double-blind, placebo-controlled, parallel-group study. The primary endpoints for evaluating efficacy include the change from baseline in seated systolic blood pressure (SBP) at Week 8 and achieving specific outcomes at Week 8 in participants with certain baseline characteristics. Secondary endpoints include changes from baseline in seated SBP at Week 52, percent change from baseline in plasma renin activity (PRA) at Week 52, achieving serum potassium levels of ≥ 3.7 mmol/L without supplementation at Week 8, percent change in PRA at Week 8, achieving 24-hour urine aldosterone levels of < 10 μg at Week 8, and changes in 24-hour urine albumin at Week 8.

Measurements will be conducted at specified timepoints, including Week 8 and Week 52, using validated methods such as automated office blood pressure monitoring (AOBPM) for SBP and central laboratory assessments for serum potassium levels. The study will involve adult participants with a documented diagnosis of Primary Aldosteronism, who meet specific inclusion criteria, such as a stable regimen of antihypertensive medications and a mean seated SBP of ≥ 135 mmHg. The trial is designed to ensure rigorous assessment of Baxdrostat's efficacy in comparison to placebo, with a focus on both blood pressure control and biochemical markers relevant to the condition.