Baxdrostat and Ventricular Remodeling

1. Individuals ≥18 years of age who are willing and able to provide signed informed consent
2. History of hypertension (Systolic BP >140 and \<170 mmHg)
3. Serum K+ ≥3.5 and \<5.0 mmol/L at Screening

4. Evidence of left ventricular (LV) hypertrophy ≤12 months prior to or at screening showing at least one (≥1) of the following:

   • Interventricular septal (IVS) thickness by echocardiography: Female ≥1.2 cm or Male ≥1.3 cm
   • Posterior wall (PW) thickness by echocardiography: Female ≥1.2 cm or Male ≥1.3 cm
   • Left ventricular mass indexed to baseline body surface area (LVMi) by echocardiography: Female >95 g⁄m\^2 or Male >115 g⁄m\^2
   • LVMi by cMRI: Female >68 g⁄m\^2 or Male >85 g⁄m\^2

5. The presence of ≥1 of the following risk factors:

   • Documented type 2 diabetes mellitus or a glycated hemoglobin (A1C) level ≥6.5%
   • Estimated glomerular filtration rate (eGFR) 45-60 mL/min/1.73m\^2 at Screening
   • Urine albumin-creatinine ratio (UACR) ≥3 mg/mmol
   • IVS ≥1.4 cm
   • PW ≥1.4 cm
   • LVMi ≥105 g⁄m\^2 for female and ≥125 g⁄m\^2 for male individuals (by echocardiography)
   • History of HFpEF (LV ejection fraction ≥50%)
   • NT-proBNP ≥125 pg/mL (within past 6 months)

6. Female individuals who are of childbearing age can only be considered eligible if:

   • they are postmenopausal (amenorrhoeic for ≥12 months following cessation of exogenous hormonal treatment) or have had a surgical procedure (eg. hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) ≥6 months at Screening that prevents them from becoming pregnant or
   • the result of their pregnancy test at the baseline visit is negative, and they agree to use at least one highly effective and one effective contraception method to avoid pregnancy during the 30 days before randomization, throughout the research study, and for at least 30 days after taking the last dose of the assigned IP

EXCLUSION

1. Considered unsuitable by the investigator for any reason that may either place the participant at increased risk during participation or interfere with the interpretation of the study outcomes
2. Female individuals who are pregnant, or can get pregnant, are breast-feeding or are planning to breastfeed and are/will not be using at least one highly effective contraception method (see Inclusion Criteria section for definitions) during the 30 days before Randomization, throughout the research study, and for at least 30 days after taking the last dose of the assigned IP
3. Upper arm circumference \<18 cm or >43 cm at Screening
4. Body mass index >40 kg/m\^2 (Image quality and accurate assessment of cardiac function degrades with obesity across all imaging modalities. Although CMR-derived images are the least compromised by high body mass indexes, MRI bore sizes and table weight limits, greater safety risks [eg. thermal burns] as well as increased frequencies of claustrophobia remain major challenges.
5. Contraindication or inability to undergo CMR scan
6. Serum Na+ level \<135 mmol/L at Screening
7. A1C >10% if living with T2DM during the 30 days before Randomization

8. At Screening

   • Systolic BP ≤120 mmHg
   • Heart rate >110 or \<45 bpm per electrocardiogram (ECG) performed at Screening
   • eGFR \<45 mL/min/1.73m\^2 at Screening
   • New York Heart Association (NYHA) functional HF class IV

9. At Screening or first IP intake

   • White blood cell (WBC) count >15 X 10\^9/L or absolute neutrophil count \<1 X 10\^9/L
   • Hemoglobin (Hb) \<100 g/L and/or anticipated initiation of erythropoietin-stimulating agents and/or planned transfusion within 60 days after screening
   • Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3X upper limits of normal (ULN) with a corresponding bilirubin >34 μmol/L unless the potential participant has a history of Gilbert syndrome

10. Medical history

    • Planned dialysis or kidney transplant during this research study
    • Adrenal insufficiency
    • Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including chronic obstructive pulmonary disease
    • Secondary causes of hypertension eg. Cushing's syndrome, aortic coarctation, renal artery stenosis, uncontrolled hyperthyroidism, untreated hyperthyroidism, hypothyroidism or pheochromocytoma
    • HF due to infiltrative cardiomyopathy (eg. sarcoid, amyloid), arrhythmogenic right ventricular (RV) cardiomyopathy, Takutsubo cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, uncorrected more than moderate primary valve disease
    • Acute coronary syndrome, myocardial infarction, stroke, unstable angina pectoris, hypertensive encephalopathy, transient ischemic attack, or hospitalization for HF, during the 30 days before Screening
    • Persistent atrial fibrillation, left bundle branch block or any cardiac arrhythmia requiring treatment
    • Severe hepatic impairment, defined as Child-Pugh Class C, based on records that confirm documented medical history
    • Clinical evidence of, or suspicion of, active infection (at the discretion of the Site Investigator)

11. Surgical history

    • Undergone a major cardiovascular surgical procedure (eg. percutaneous coronary intervention/coronary artery bypass grafting or percutaneous coronary
    • Intervention/coronary artery bypass grafting) or major endoscopic procedure (thoracoscopic or laparoscopic) during the 60 days before Randomization
    • Previous or planned coronary, carotid, or peripheral artery revascularization during the 45 days before Screening
    • Prior solid organ transplant and/or cell transplants
    • Previous cardiac device implant (eg. implantable cardioverter defibrillator/cardiac resynchronization therapy/pacemaker) or planned device implant ≤90 days after screening
12. Prior treatment (within 30 days before Screening) with or currently on an angiotensin-receptor blocker (ARB) in combination with an angiotensin converting enzyme inhibitor (ACEi)
13. Prior treatment (within 30 days before Screening) with or currently on a mineralocorticoid receptor antagonist (MRA) or a K+-sparing diuretic, or anticipated initiation of either of these agents during the study period
14. Unwilling to discontinue taking K+ supplements
15. On K+ binders within 30 days prior to Screening
16. On or expected to initiate a strong cytochrome P450 3A (CYP3A) inducer (eg. carbamazepine, enzalutamide, mitotane, phenytoin, rifabutin, rifampin and St. John's wort)
17. Prior treatment within 6 months prior to Screening with a cytotoxic therapy (eg. cisplatin, doxorubicin, etoposide, misoprostol, trastuzumab)
18. Known hypersensitivity to baxdrostat or drugs of the same class or any of its excipients
19. Participation in another clinical study involving the investigational drug within 30 days prior to Screening or has plans to participate in another clinical study within 30 days of discontinuing the investigational drug