HRS-1780 for people with uncontrolled or resistant high blood pressure

Inclusion Criteria:

1. Male or female, aged ≥ 18 and \< 80 years ；
2. Mean trough seated SBP ≥ 140 mmHg and \< 170 mmHg at both screening and randomization visits.
3. Meet one of the following two criteria:

   1. Meet the criteria for uncontrolled hypertension；
   2. Meet the criteria for resistant hypertension；
4. Serum potassium ≥ 3.5 mmol/L and ≤ 5.0 mmol/L ；
5. Voluntarily sign the ICF prior to the study；
6. Have no plan for fertility from the time of signing the ICF until 4 weeks after the last dose.

Exclusion Criteria:

1. Mean trough seated DBP ≥ 110 mmHg at randomization.
2. Have a known secondary cause of hypertension, including but not limited to: renal artery stenosis, coarctation of the aorta, uncontrolled or untreated hyperthyroidism/hypothyroidism, pheochromocytoma, or Cushing's syndrome.
3. History of adrenal insufficiency at screening.
4. Presence of severe structural heart disease at screening, including severe valvular heart disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, rheumatic heart disease, or congenital heart disease.
5. Presence of persistent atrial fibrillation or any arrhythmia requiring treatment at screening; or resting heart rate \< 45 bpm or \> 110 bpm.
6. New York Heart Association (NYHA) Class III-IV heart failure at screening.
7. Undergone CT angiography (CTA) or colonoscopy within 1 month prior to screening.
8. Undergone percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 6 months prior to screening, or plan to undergo PCI, CABG, carotid or peripheral artery revascularization during the study period.
9. History of stroke, acute coronary syndrome, hypertensive encephalopathy, or hospitalization for heart failure within 6 months prior to screening.
10. Within 6 months prior to screening, presence of clinically significant diseases in the following systems that, in the investigator's judgment, may interfere with the study results or pose additional risk to the administration of the investigational product, including but not limited to: respiratory, digestive, endocrine, immune, urinary, hematologic, neurologic, or psychiatric disorders.
11. History of malignancy within 5 years prior to screening.
12. Use of strong inhibitors/inducers of cytochrome P450 3A4 (CYP3A4) within 1 week prior to screening ,or moderate inhibitors/inducers.
13. Use of mineralocorticoid receptor antagonists (MRAs) and/or potassium-sparing diuretics (e.g., spironolactone, eplerenone, finerenone, amiloride, triamterene, etc.) within 4 weeks prior to randomization.
14. Use of aldosterone synthase inhibitors (ASIs) within 4 weeks prior to randomization.
15. Concomitant use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) within 4 weeks prior to randomization.
16. Treatment with potassium binders within 2 months prior to screening.
17. Presence of any of the following laboratory abnormalities:

    1. eGFR \< 45 mL/min/1.73 m² ;
    2. HbA1c \> 10.5%;
    3. Serum sodium \< 135.0 mmol/L;
    4. ALT ≥ 3 × ULN;
    5. AST ≥ 3 × ULN;
    6. Total bilirubin ≥ 2 × ULN.
18. Body mass index (BMI) \> 35 kg/m².
19. Run-in period placebo compliance \< 80% or \> 120% at randomization.
20. Known or suspected allergy to MRAs, the investigational product, or any of its excipients.
21. Treatment with any other investigational product within 90 days or 5 half-lives prior to screening .
22. Women of childbearing potential (WOCBP) who are pregnant, breastfeeding, plan to become pregnant during the study, or are unable to use highly effective contraceptive measures; or male participants who are unable to use highly effective contraceptive measures.
23. Occupation or working schedule requiring regular night shifts or similar circumstances that may interfere with study procedures.
24. Any other condition that, in the investigator's judgment, may compromise participant safety or interfere with the assessment of study results.