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

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of SAL0120 Tablets in Patients Uncontrolled Hypertension on Two or More Medications

This is a Phase II, multicentre, randomised, double-blinded, placebo-controlled, parallel group study to evaluate the safety, and effect of low, middle and high dose of SAL0120 versus placebo, administered once daily (QD) orally, on the reduction of systolic blood pressure in approximately 256 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).

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