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

Inclusion criteria

• Age 18 to 75 years (inclusive), male or female
• Diagnosis of essential hypertension
• Mean seated systolic blood pressure (msSBP) ≥ 140 mmHg and < 180 mmHg at screening
• At screening, subjects must meet one of the following criteria (A or B):

A: Uncontrolled hypertension (uHTN)

• Receiving a stable regimen of the following antihypertensive drugs at the maximum tolerated dose for at least 4 weeks prior to screening (as combination therapy or single-pill combination), as judged by the investigator, and in whom an additional antihypertensive agent is considered at screening:

ACEI/ARB/ARNI + diuretic CCB + diuretic Beta-blockers used for the treatment of other conditions (e.g., migraine, heart failure, coronary artery disease) are not considered antihypertensive agents.

B: Resistant hypertension (rHTN):

• Receiving a stable regimen of the following antihypertensive drugs at the maximum tolerated dose for at least 4 weeks prior to screening (as combination therapy or single-pill combination), as judged by the investigator, and in whom an additional antihypertensive agent is considered at screening:

ACEI/ARB/ARNI + CCB + diuretic ACEI/ARB/ARNI + CCB + diuretic + beta-blocker/aldosterone receptor antagonist/centrally acting agent/alpha-blocker Beta-blockers used for the treatment of other conditions (e.g., migraine, heart failure, coronary artery disease) are not considered antihypertensive agents.

• msSBP ≥ 140 mmHg and < 180 mmHg at the end of the single-blind run-in period or prior to randomization
• All male subjects and female subjects of childbearing potential agree to use highly effective contraceptive methods from the date of signing the ICF until 1 month after discontinuation of study treatment.

Exclusion criteria

• Severe hypertension (msSBP ≥ 180 mmHg and/or msDBP ≥ 110 mmHg); malignant hypertension, hypertensive emergency, hypertensive crisis, or hypertensive encephalopathy;
• History or diagnostic evidence of secondary hypertension, including but not limited to: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary aldosteronism, Cushing's syndrome, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension;
• Medication compliance < 80% or > 120% during the single-blind run-in period;
• Clinically significant laboratory abnormalities, including but not limited to: serum ALT and/or AST > 2.5 × upper limit of normal (ULN); total bilirubin > 2 × ULN; eGFR < 30 mL/min/1.73 m² estimated by the simplified Modification of Diet in Renal Disease (MDRD) equation; any clinically significant laboratory abnormality that, in the investigator's opinion, may interfere with the evaluation of efficacy and/or safety data of this study; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1c > 8.0%);
• Severe obesity with body mass index (BMI) > 40 kg/m² (BMI = weight (kg) / height² (m²));
• Hemoglobin < 100 g/L, or blood transfusion for anemia within 3 months prior to screening;
• Subjects with a documented history of anxiety or depression;
• Female subjects who are pregnant, breastfeeding, or have a positive pregnancy test