Assess Sacubitril/Allisartan and Amlodipine in Patients With Essential Hypertension Uncontrolled With Amlodipine

Prior treatment

• Concomitant use of three or more types of antihypertensive agents.
• History of substance abuse or excessive alcohol consumption within 6 months prior to screening.
• Blood donation or major blood loss (\>400 mL) within 3 months prior to screening, or clinically diagnosed hypovolemia.
• Participation in any interventional clinical trial with investigational medicinal product or medical device within 3 months prior to screening.
• Drug compliance during run-in period \<80% or \>120%.

Other illness

• Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg).
• History or confirmed diagnosis of secondary hypertension.
• Personal history of angioedema induced by drugs or other causes.
• Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus .
• Subjects with active malignant tumor.
• Any other conditions deemed inappropriate for trial enrollment by the investigator that may interfere with efficacy and/or safety evaluation of the study, including but not limited to anticipated poor subject compliance or impractical regular follow-up due to long residential distance.

Lab values

• Clinically significant abnormal laboratory findings, including but not limited to: serum potassium \>5.5 mmol/L or \<3.5 mmol/L; serum ALT and/or AST \>2.5 × upper limit of normal (ULN); serum creatinine \>1.5 × ULN; any other clinically significant laboratory abnormality deemed by the investigator likely to confound efficacy and/or safety assessment of the study.

• Patients 18-75 years old.
• Confirmed diagnosis of essential hypertension.
• Patients who meet one of the following criteria when screening:
  • Treatment-naive patients (newly diagnosed essential hypertension, or patients with a prior hypertension history who have not taken any antihypertensive medication for at least 4 weeks prior to screening): mean seated systolic blood pressure (msSBP) ≥150 mmHg and \<180 mmHg.
  • Patients with irregular oral administration of amlodipine besylate (5 mg once daily) (treatment duration less than 4 weeks before screening, or more than 5 missed dosing days within the 4 weeks prior to screening): msSBP ≥140 mmHg and\<180 mmHg.
  • Patients on existing stable antihypertensive therapy (receiving a stable dose of another single-agent antihypertensive, free combination of two single-agent drugs, or single-pill fixed-dose combination containing two active ingredients for at least 4 weeks prior to screening): msSBP ≥140 mmHg and \<180 mmHg, and the physician determines that switching treatment to amlodipine besylate (5 mg once daily) is clinically appropriate.
  • Patients with essential hypertension who have been regularly treated with amlodipine besylate (5mg once daily) for ≥4 weeks and have msSBP ≥140 mmHg and\<180 mmHg. The previously regularly administered product shall be Norvasc® or generic amlodipine besylate that has passed the generic consistency evaluation in China.
• At randomization, subjects must have msSBP ≥140 mmHg and \<180 mmHg.
• Subjects voluntarily participate in the trial and sign the written informed consent form.
• For subjects enrolled for ambulatory blood pressure monitoring (ABPM): in addition to all above inclusion criteria, one further requirement must be satisfied: valid ABPM report with a 24-hour average blood pressure ≥130/80 mmHg. (Subjects failing to meet Criterion 6 remain eligible for the main trial without ABPM testing.)