A Pivotal Study to Evaluate the Efficacy of Lorundrostat in Subjects With Uncontrolled Hypertension on a Standardized Antihypertensive Medication Regimen

Inclusion Criteria: Written informed consent, obtained before any assessment is performed At least 18 years of age at the time of signing the informed consent form At Screening: AOBP SBP of 140-180 mmHg and AOBP DBP of 65-110 mmHg, or AOBP DBP of 90-110 mmHg At Randomization: AOBP SBP of 135-180 mmHg and AOBP DBP of 65-110 mmHg, or AOBP DBP of 85-110 mmHg At Randomization: ABPM 24-hour mean SBP of 130-180 mmHg Taking between 2 and 5 AHT medications, inclusive, at Screening. Note: each individual AHT agent in a combination pill counts as one AHT medication History of hypertension lasting at least 6 months prior to Randomization Serum cortisol (morning measurement, blood draw as close to 8 am as possible and before 10 am) between 3 and 22 µg/dL, inclusive, at Screening Body mass index (BMI) of 18-40 kg/m2 at Screening Fertile male subjects and female subjects of childbearing potential, and their partners, must agree to use either highly effective or acceptable methods of contraception from the screening visit to 28 days after the last dose of study drug Willing and able to comply with the study instructions and attend all scheduled study visits Exclusion Criteria: Women who are pregnant, plan to become pregnant, or are breast-feeding Subjects with known hypersensitivity to lorundrostat or any of the excipients Previous treatment with lorundrostat or other aldosterone synthase inhibitors within 3 months prior to Screening Participation in a trial involving an investigational AHT therapy within 6 months prior to Screening, or any trial involving an investigational device or drug within 4 weeks prior to Screening Known allergy or intolerance to angiotensin receptor blockers, dihydropyridine calcium channel blockers, or thiazide-type diuretics Prescribed any standard AHT cardiovascular medication for other chronic conditions such that discontinuation might pose serious risk to health in the opinion of the investigator eGFR <45 mL/min/1.73 m2 at Screening Serum potassium >4.8 mmol/L at Randomization Serum sodium <135 mmol/L at Screening (rescreening of subjects with an exclusionary serum sodium is prohibited) History of clinically significant hyponatremia History of adrenal insufficiency Use of ENaC inhibitors or mineralocorticoid receptor antagonists, including, but not limited to amiloride, triamterene, spironolactone, eplerenone within 4 weeks prior to Screening Hospitalization for the treatment of severely elevated blood pressure within 12 months prior to Screening Current, known or presumed white coat hypertension/significant white coat effect (>20 mmHg elevation in clinic BP compared with historical home BP assessments, or documented >20 mmHg elevation in clinic compared with historical 24-hour ABPM measurements) Current, known or presumed orthostatic hypotension (as defined in the SRM) Current, known or presumed autonomic dysfunction Current night-shift worker, or anticipated to become a night-shift worker for >14 days continuously during the duration of the study Arm circumference >55 centimeters at Screening Previously proven secondary cause of hypertension (NOTE: subjects with primary aldosteronism are eligible for participation) Classified as being in New York Heart Association (NYHA) Class IV at Screening History of myocardial infarction, stroke, or transient ischemic attack within one year prior to Screening Known left ventricular ejection fraction <40% within 1 year prior to Screening Known nephrotic syndrome or severely increased albuminuria (urine albumin-creatinine ratio [UACR] > 3000 mg/g) Diabetes mellitus subjects with evidence of Type IV renal tubular acidosis Diabetes mellitus with a glycosylated hemoglobin (HbA1c) >9% (>74.9 mmol/mol) at Screening Diabetes mellitus with >1 severe hypoglycemic event or severe diabetic ketoacidosis event (events requiring external help) in the 12 months prior to Screening, or with a history of impaired hypoglycemia awareness at Screening Any major episode of infection requiring hospitalization and/or treatment with intravenous (IV) anti-infective agents during the 2 months prior to Randomization Planned major surgery requiring hospitalization during the study period, or performed within 4 weeks prior to Screening History of malignant neoplasms within the past 5 years prior to Screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed Inability to discontinue regular use of proton pump inhibitors from the AHT run-in period Known or suspected abuse of illicit drugs or alcohol within 1 year prior to Screening In the opinion of the Principal Investigator, any other condition that will preclude participation in the study