This study is a Phase 2 trial to evaluate the blood pressure-lowering effects of lorundrostat (an aldosterone synthase inhibitor), administered on a background of a standardized anti-hypertensive (AHT) medication regimen, in subjects with uncontrolled hypertension. The study consists of a standardized AHT regimen run-in phase with single blind lorundrostat placebo (subject is blinded) followed by a randomized, double-blind, placebo-controlled, parallel arm phase, after which subjects will be offered the opportunity to participate in an open-label extension (OLE) with an initial 4-week randomized double-blind treatment withdrawal phase. Any subject electing to not participate in the OLE will undergo an end of study visit to complete their participation in the study.

The study will be conducted at approximately 60 centers across the United States.

Inclusion Criteria:

1. Written informed consent, obtained before any assessment is performed
2. At least 18 years of age at the time of signing the informed consent form
3. At Screening: AOBP SBP of 140-180 mmHg plus AOBP DBP of 65-110 mmHg, or AOBP DBP of 90-110 mmHg
4. At Randomization: AOBP SBP of 135-180 mmHg plus AOBP DBP of 65-110 mmHg, or AOBP DBP of 85-110 mmHg
5. At Randomization: ABPM 24-hour mean SBP of 130-180 mmHg plus ABPM DBP of 65-110 mmHg, or ABPM DBP of 80-110 mmHg
6. Taking between 2 and 5 AHT medications, inclusive, at Screening. Note: each individual AHT agent in a combination pill counts as one AHT medication
7. History of hypertension lasting at least 6 months prior to randomization
8. 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
9. Body mass index (BMI) of 18-40 kg/m2 at screening
10. 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
11. Willing and able to comply with the study instructions and attend all scheduled study visits

Exclusion Criteria:

1. Women who are pregnant, plan to become pregnant, or are breast-feeding
2. Subjects with known hypersensitivity to lorundrostat or any of the excipients
3. Previous treatment with lorundrostat or other aldosterone synthase inhibitors within 3 months prior to the screening visit
4. 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
5. Known allergy or intolerance to angiotensin receptor blockers, dihydropyridine calcium channel blockers, or thiazide-type diuretics
6. Prescribed any standard antihypertensive cardiovascular medication for other chronic conditions such that discontinuation might pose serious risk to health in the opinion of the investigator
7. eGFR <45 mL/min/1.73 m2 at the screening visit
8. Serum potassium >4.8 mmol/L at the screening visit
9. Serum sodium <135 mmol/L at the screening visit (Rescreening of subjects with an exclusionary serum sodium is prohibited)
10. History of clinically significant hyponatremia
11. History of adrenal insufficiency
12. Use of ENaC inhibitors or mineralocorticoid receptor antagonists, including, but not limited to amiloride, triamterene, spironolactone, eplerenone within 4 weeks prior to the screening visit
13. Hospitalization for the treatment of severely elevated blood pressure within 12 months prior to the screening visit
14. Current, known or presumed white coat hypertension / significant white coat effect (>20 mmHg elevation in clinic blood pressure compared with historical HBPM assessments, or documented >20 mmHg elevation in clinic compared with historical 24-hour ABPM measurements)
15. Current, known or presumed orthostatic hypotension
16. Current, known or presumed autonomic dysfunction
17. Current night-shift worker, or anticipated to become a night-shift worker for >14 days continuously during the duration of the study
18. Arm circumference >55 centimeters at the screening visit
19. Previously proven secondary cause of hypertension (NOTE: subjects with primary aldosteronism are eligible for participation)
20. Classified as being in New York Heart Association (NYHA) Class IV at the screening visit
21. History of myocardial infarction, stroke, or transient ischemic attack within one year prior to screening
22. Known left ventricular ejection fraction <40% within 1 year of screening visit
23. Known nephrotic syndrome or severely increased albuminuria (UACR > 300mg/g)
24. Diabetes mellitus subjects with evidence of Type IV renal tubular acidosis
25. Diabetes mellitus with a HbA1c >9% (>74.9 mmol/mol) at screening
26. 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
27. Any major episode of infection requiring hospitalization and/or treatment with IV anti-infective agents during the 2 months prior to randomization
28. Planned major surgery requiring hospitalization during the study period, or performed within 4 weeks prior to the screening visit
29. 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
30. Inability to discontinue regular use of proton pump inhibitors from the AHT run-in period.
31. Known or suspected abuse of illicit drugs or alcohol within 1 year prior to screening
32. In the opinion of the Principal Investigator, any other condition that will preclude participation in the study