A Study to Investigate the Effect of Baxdrostat on Ambulatory Blood Pressure in Participants With Resistant Hypertension

Study Overview
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Brief Summary
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This is a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and the effect of 2 mg Baxdrostat vs. placebo, administered QD orally, on the reduction of SBP, measured by average 24-hour ABPM in 212 participants with rHTN (defined as seated SBP ≥ 140 mmHg at Screening and mean ambulatory SBP ≥ 130 mmHg at baseline, despite a stable regimen of ≥ 3 antihypertensive agents, one of which is a diuretic).

Detailed Description
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This is a Phase III, multicentre, randomised, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and the effect of 2 mg baxdrostat versus placebo, administered once a day (QD) orally, on the reduction of ambulatory SBP in participants with rHTN, defined as BP targets not being achieved in an individual despite the use of at least 3 antihypertensive agents of different classes (at maximum tolerated dose in the judgement of the Investigator), one of which is a diuretic.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Effect of Baxdrostat on Ambulatory Blood Pressure in Participants With Resistant Hypertension

Conditions
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Resistant Hypertension

Intervention / Treatment
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* Drug: Baxdrostat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be ≥ 18 years old, at the time of signing the informed consent. Mean seated SBP on AOBPM of ≥ 140 mmHg and < 170 mmHg at Screening. Have a stable regimen of ≥ 3 antihypertensive medications, from different therapeutic classes (at least one should be a diuretic), at maximum tolerated dose in the judgement of the Investigator, for at least 4 weeks prior to Screening (participants who do not meet this criterion may be rescreened at the Investigator's discretion). Beta blockers used to treat other conditions (ie, migraine, HF, coronary artery disease) should not be counted as an antihypertensive medication for the purpose of qualifying for this study. Have eGFR ≥ 45 mL/min/1.73 m2 at Screening. Serum potassium (K+) level ≥ 3.5 and < 5.0 mmol/L at Screening, determined as per central laboratory Randomization Criteria: mean ambulatory SBP of ≥ 130 mmHg at randomisation. Exclusion Criteria: Mean seated SBP on AOBPM ≥ 170 mmHg at Screening. Mean seated DBP on AOBPM ≥ 110 mmHg at Screening. Serum sodium level < 135 mmol/L at Screening, as per central laboratory. Participant has the following known secondary causes of hypertension: renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, pheochromocytoma, Cushing's syndrome, aortic coarctation. New York Heart Association functional HF class IV at Screening. Persistent atrial fibrillation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 mg baxdrostat<br>2 mg baxdrostat administered orally, once daily (QD). | Drug: Baxdrostat<br>* Baxdrostat tablet administered orally, once daily (QD). Unit dose strength: • 2 mg per tablet.<br>* Other names: CIN-107;|
| Placebo Comparator: Placebo<br>Placebo administered orally, once daily (QD) | Drug: Placebo<br>* Placebo tablet matching baxdrostat, administered orally, once daily (QD).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ambulatory 24-hour average SBP | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory 24-hour average SBP at Week 12. | At Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ambulatory night-time average SBP | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory night-time average SBP at Week 12. | At Week 12 | 
| Change from baseline in ambulatory daytime average SBP | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory daytime average SBP at Week 12. | At Week 12 | 
| Change from baseline in seated SBP | To assess the effect of treatment with baxdrostat 2 mg versus placebo on seated SBP at Week 12. | At Week 12 | 
| Participants achieving ambulatory 24-hour average SBP of < 130 mmHg | To assess the effect of treatment with baxdrostat 2 mg versus placebo on achieving ambulatory 24-hour average SBP < 130 mmHg at Week 12. | At Week 12 | 
| Change from baseline in ambulatory 24-hour average DBP | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory 24-hour average DBP at Week 12. | At Week 12 | 
| Change from baseline in ambulatory night-time average DBP | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory night-time average DBP at Week 12. | At Week 12 | 
| Change from baseline in the average ambulatory daytime average DBP | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory daytime average DBP at Week 12. | At Week 12 | 
| Change from baseline on seated DBP | To assess the effect of treatment with baxdrostat 2 mg versus placebo on seated DBP at Week 12. | At Week 12 | 
| Achieving a nocturnal SBP dipping of ≥ 10% | To assess the effect of treatment with baxdrostat 2 mg versus placebo in the nocturnal dipping pattern at Week 12. | At Week 12. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Resistant hypertension, Blood pressure, Baxdrostat, CIN-107, Aldosterone, Aldosterone synthase, Aldosterone synthase inhibitor