A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension

Study Overview
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Brief Summary
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This is a Phase III, multicentre, randomised, double-blinded, placebo-controlled, parallel group study to evaluate the safety, tolerability and effect of 1 or 2 mg baxdrostat versus placebo, administered once daily (QD) orally, on the reduction of systolic blood pressure in approximately 720 participants aged ≥ 18 years with hypertension, despite a stable regimen of 2 antihypertensive agents at baseline, one of which is a diuretic (uncontrolled hypertension); or ≥ 3 antihypertensive agents at baseline, one of which is a diuretic (treatment-resistant hypertension).

Official Title
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A Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension

Conditions
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Uncontrolled Hypertension, 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: Male or female participants must be ≥ 18 years old Mean sitting systolic blood pressure on automated office blood pressure measurement ≥ 140 mmHg and < 170 mmHg at Screening Fulfil at least 1 of the following 2 criteria: uHTN subpopulation: have a stable regimen of 2 antihypertensive medications, from different therapeutic classes (at least one should be a diuretic), at maximum tolerated dose in the judgement of the Investigator rHTN subpopulation: 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 Estimated glomerular filtration rate ≥ 45 mL/min/1.73m2 at Screening Serum potassium (K+) level ≥ 3.5 and < 5.0 mmol/L at Screening Randomisation Criterion: Sitting systolic blood pressure on attended automated office blood pressure measurement of ≥ 135 mmHg at baseline Exclusion Criteria: Mean sitting systolic blood pressure on attended automated office blood pressure measurement ≥ 170 mmHg at Randomisation Mean seated diastolic blood pressure on attended automated office blood pressure measurement ≥ 110 mmHg at Randomisation Serum sodium level < 135 mmol/L at Screening 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 heart failure 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 strengths: 1 mg per tablet for 1 mg baxdrostat Arm; 2 mg per tablet for 2 mg baxdrostat Arm.<br>* Other names: CIN-107;|
| Experimental: 1 mg baxdrostat<br>1 mg baxdrostat administered orally, once daily (QD). | Drug: Baxdrostat<br>* Baxdrostat tablet administered orally, once daily (QD). Unit dose strengths: 1 mg per tablet for 1 mg baxdrostat Arm; 2 mg per tablet for 2 mg baxdrostat Arm.<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 seated systolic blood pressure for 2 mg baxdrostat | To assess the effect of 2 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12 | At Week 12 | 
| Change from baseline in seated systolic blood pressure for 1 mg baxdrostat | To assess the effect of 1 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12 | At Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from randomised withdrawal baseline (Week 24) in seated systolic blood pressure (SBP) for 2 mg baxdrostat | To assess the effect of 2 mg baxdrostat vs placebo on seated systolic blood pressure (SBP) at 8 weeks after randomised withdrawal | At Week 32 | 
| Change from baseline in seated SBP for 2 mg baxdrostat | To assess the effect of 2 mg baxdrostat vs placebo on seated SBP at Week 12 in the resistant hypertension (rHTN) subpopulation | At Week 12 | 
| Change from baseline in seated diastolic blood pressure (DBP) for 2 mg baxdrostat | To assess the effect of 2 mg baxdrostat vs placebo on seated diastolic blood pressure (DBP) at Week 12 | At Week 12 | 
| Achieving seated SBP < 130 mmHg for 2 mg baxdrostat | To assess the effect of 2 mg baxdrostat vs placebo on achieving seated SBP < 130 mmHg at Week 12 | At Week 12 | 
| Change from baseline in seated SBP for 1 mg baxdrostat | To assess the effect of 1 mg baxdrostat vs placebo on seated SBP at Week 12 in the rHTN subpopulation | At Week 12 | 
| Change from baseline in seated DBP for 1 mg baxdrostat | To assess the effect of 1 mg baxdrostat vs placebo on seated DBP at Week 12 | At Week 12 | 
| Achieving seated SBP < 130 mmHg for 1 mg baxdrostat | To assess the effect of 1 mg baxdrostat vs placebo on achieving seated SBP < 130 mmHg at Week 12 | At Week 12 | 
| The change from baseline in the mean ambulatory 24-hour SBP as measured by ambulatory blood pressure monitoring (ABPM) for 2 mg baxdrostat | To assess the effect of treatment with baxdrostat 2 mg vs placebo on ambulatory 24-hour average SBP at Week 12 | At Week 12 | 
| The change from baseline in the mean ambulatory 24-hour SBP as measured by ABPM for 1 mg baxdrostat | To assess the effect of treatment with baxdrostat 1 mg vs placebo on ambulatory 24-hour average SBP 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, Uncontrolled hypertension, Resistant hypertension, Blood pressure, Baxdrostat, CIN-107, Aldosterone, Aldosterone synthase