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

Efficacy and Safety of Sacubitril/Allisartan and Amlodipine in Patients With Essential Hypertension Uncontrolled With Amlodipine: A Phase III, Multicenter, Randomized, Double-blind, Parallel-controlled, 52-week Clinical Study

The main objective of the study will be to assess the efficacy and safety of Sacubitril/Allisartan (240mg) and Amlodipine (5mg) in patients with essential hypertension uncontrolled after 4-week treatment with Amlodipine (5mg).

Inclusion Criteria:

1. Patients 18-75 years old.

2. Confirmed diagnosis of essential hypertension.

3. Patients who meet one of the following criteria when screening:

   A. 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.

   B. 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.

   C. 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.

   D. 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.

4. At randomization, subjects must have msSBP ≥140 mmHg and <180 mmHg.

5. Subjects voluntarily participate in the trial and sign the written informed consent form.

6. 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.)

Exclusion Criteria:

1. Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg).
2. History or confirmed diagnosis of secondary hypertension.
3. Concomitant use of three or more types of antihypertensive agents.
4. Personal history of angioedema induced by drugs or other causes.
5. 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.
6. Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus .
7. Subjects with active malignant tumor.
8. History of substance abuse or excessive alcohol consumption within 6 months prior to screening.
9. Blood donation or major blood loss (>400 mL) within 3 months prior to screening, or clinically diagnosed hypovolemia.
10. Participation in any interventional clinical trial with investigational medicinal product or medical device within 3 months prior to screening.
11. Drug compliance during run-in period <80% or >120%.
12. 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.