Inclusion Criteria:
1. Subjects who are able to understand and willing to strictly follow the clinical trial protocol to complete the study, and have signed the informed consent form.
2. Male or female aged 18 to 75 years (inclusive), with a body mass index (BMI) ≤ 30 kg/m².
3. Patients with moderate to severe essential hypertension:
1. Newly diagnosed essential hypertension or a history of hypertension but no antihypertensive medication within 4 weeks prior to screening. Qualified subjects will enter the placebo run-in period. The subject's blood pressure at the Screening Visit (V1) and Baseline (V3) must meet the following criteria: at V1, mean sitting systolic blood pressure (msSBP) \> 140 mmHg and/or mean sitting diastolic blood pressure (msDBP) \> 90 mmHg; at V3, 160 mmHg ≤ msSBP \< 190 mmHg and/or 100 mmHg ≤ msDBP \< 120 mmHg.
2. Subjects who have been taking antihypertensive medications other than the study drugs as regularly as possible (missed doses ≤ 2 per week) for at least 4 weeks prior to screening, but whose blood pressure remains uncontrolled. After qualifying, subjects will discontinue their previous medications on the day they enter the placebo run-in period. Blood pressure criteria at V1 and V3 must meet: V1 msSBP \> 140 mmHg and/or msDBP \> 90 mmHg; V3 160 mmHg ≤ msSBP \< 190 mmHg and/or 100 mmHg ≤ msDBP \< 120 mmHg. \[Note: "Study drugs" here refer to all investigational treatments in this study (excluding placebo) and other marketed drugs with identical active ingredients, mainly including valsartan 160 mg, sacubitril/valsartan sodium 200 mg, and azilsartan medoxomil potassium 40 mg.\]
4. Subjects who are able to communicate and comply with all study requirements, and demonstrate good medication adherence.
5. The subject and their sexual partner are willing to have no plans for pregnancy and voluntarily use effective contraception from 2 weeks before screening until 6 months after the last dose of study drug, have no plans for sperm or egg donation, and agree to use one or more non-pharmacological contraceptive measures during sexual intercourse from 2 weeks before screening until 1 month after the last dose of study drug
Exclusion Criteria:
1. Known or suspected secondary hypertension (including but not limited to: primary aldosteronism, pheochromocytoma, Cushing's syndrome, renal hypertension, drug-induced hypertension, etc.).
2. Known history of orthostatic hypotension or frequent hypotension after taking antihypertensive medications.
3. Planned or concomitant use of other antihypertensive drugs (other than study drugs) during the trial, such as calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), diuretics, β-blockers, α-blockers, vasodilators, or traditional Chinese medicines with antihypertensive effects.
4. Planned or concomitant use of non-antihypertensive drugs that may affect blood pressure during the trial. Note: Topical, ophthalmic, intra-articular, intranasal, and inhaled glucocorticoids (with very low systemic absorption) are allowed. Short-term (≤3 days) systemic glucocorticoid use (intravenous or oral) for prophylaxis (e.g., contrast agent allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity to contact allergens) is permitted; however, systemic glucocorticoids must not be used within 7 days before the primary endpoint.
5. Planned or concomitant use of drugs that may affect the metabolism of the investigational drug or comparator, as well as other chemical drugs, biological products, traditional Chinese medicines, or natural medicines deemed unsuitable by the investigator.
6. History of severe cerebrovascular disease within 6 months prior to enrollment, such as hypertensive encephalopathy, cerebrovascular injury, cerebral hemorrhage, transient ischemic attack, cerebral infarction, etc.
7. History of any of the following severe cardiovascular diseases within 6 months prior to enrollment: chronic heart failure (New York Heart Association \[NYHA\] Class III or IV), acute coronary syndrome, cardiogenic shock, any type of cardiomyopathy, rheumatic heart disease, arrhythmias requiring treatment, and valvular heart disease requiring treatment.
8. Severe or malignant retinopathy. Severe retinopathy is defined as retinal hemorrhage, microaneurysms, cotton-wool spots, hard exudates, or a combination thereof; malignant retinopathy is defined as severe retinopathy plus optic disc edema.
9. History of angioedema, hereditary or idiopathic angioedema.
10. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin (TBIL) \> 2 × upper limit of normal (ULN) (based on the local laboratory reference ranges); serum creatinine (Cr) \> 1.5 × ULN (based on the local laboratory reference ranges).
11. Diabetes mellitus with poor glycemic control (fasting blood glucose \> 11.1 mmol/L).
12. Severe depression, anxiety disorder, or severe sleep disorder requiring combined treatment with three or more medications within 12 months before screening.
13. Subjects with aortic aneurysm or dissecting aneurysm, history of percutaneous transluminal coronary angioplasty, or cardiac surgery.
14. History or current diagnosis of severe bronchial asthma or severe obstructive pulmonary disease.
15. Advanced peripheral arterial occlusive disease or Raynaud's syndrome.
16. History of malignancy (except for non-metastatic basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, that were diagnosed and have been stable after appropriate treatment or resection within the past 5 years).
17. History of gastrointestinal surgery that may significantly alter drug absorption, distribution, metabolism, or excretion, or presence of severe gastrointestinal disease, dysphagia, or recurrent vomiting leading to difficulty with food intake or medication administration.
18. Subjects with severe autoimmune disease (e.g., chronic rheumatoid arthritis, systemic lupus erythematosus), severe hematopoietic system disease, or severe chronic inflammatory disease requiring long-term anti-inflammatory treatment (except for those taking only low-dose aspirin ≤ 100 mg per day).
19. Participation in any interventional clinical trial within 3 months prior to screening, or plans to participate in another clinical study during this trial or within 3 months after its completion.
20. Evidence of alcohol abuse (average consumption of ≥ 14 units of alcohol per week, where 1 unit ≈ 360 mL of beer, 45 mL of spirits, or 150 mL of wine) or drug abuse within 6 months prior to screening, which in the investigator's opinion would interfere with the subject's understanding or completion of the study.
21. Positive pregnancy test, lactating women, or women planning to become pregnant.
22. Abnormal infectious disease screening results at screening that are judged by the investigator to be clinically significant and require treatment.
23. Known allergy to the study drugs, similar drugs (e.g., other combination products containing valsartan, azilsartan, or sacubitril), or related excipients.
24. Patients with severe neurological or psychiatric disorders that prevent adequate understanding and cooperation.
25. Subjects who, in the investigator's judgment, cannot tolerate the 1-week discontinuation of prior antihypertensive medications during the placebo run-in period and baseline, or those whose prior antihypertensive medications (e.g., perindopril) require a complete washout period of ≥ 2 weeks (≥ 5 half-lives) as assessed by the investigator.
26. Poor medication compliance during the placebo run-in period (defined as actual total amount of placebo taken \< 80% of the planned total dose) or other compliance issues judged by the investigator.
27. Subjects engaged in working at heights, motor vehicle driving, or operating hazardous machinery.
28. Any concurrent condition that, in the investigator's opinion, may interfere with study assessments, or participation in this study that may pose an increased risk to the subject.
29. Subjects judged by the investigator to be unsuitable for participation in this trial.
