An Efficacy, Safety, Tolerability and Dose Finding Study of XXB750 in Resistant Hypertension Patients.

Inclusion Criteria

• Male and female participants who are ≥ 18 years old.
• Signed informed consent prior to participation in the study.
• Apparent rHTN at screening (Visit 1) defined as uncontrolled BP with an office msSBP ≥ 140 mmHg despite treatment with stable (i.e., unchanged for ≥4 weeks), optimal or maximally tolerated doses of three or four antihypertensive drugs of different classes, including an ACEI/ARB, a long-acting dihydropyridine CCB, and a thiazide or thiazide-like diuretic. Participant with documented intolerance to any doses of CCBs may be eligible if receiving another class of antihypertensive medication at an optimal or maximally tolerated dose (referred to as triple background antihypertensive therapy. An optimal dose is defined as the highest dose taking in to account participant's documented comorbidities and tolerability per investigator's clinical judgment.
• Mean 24hr SBP ≥135 mmHg (measured by ABPM) at the end-of Run-in-Visit (Visit 30) on treatment with optimal or maximally tolerated doses of an ACEI/ARB, a long-acting dihydropyridine CCB (or a suitable alternative in case of intolerance per inclusion criterion above), and a thiazide or thiazide-like diuretic.

Exclusion Criteria

• Subjects with the following blood pressures at the specified time points are not eligible to participate in the study:
• Office msSBP 170 mmHg or 24h mean DBP >105mmHg measured by ABPM at the end of the run-in (Visit 30).
• Known history of secondary hypertension (moderate-to-severe obstructive sleep apnea without receiving CPAP therapy (either face mask or nasal device), renovascular hypertension, primary aldosteronism, pheochromocytoma, Cushing syndrome, aortic coarctation or other cause of secondary hypertension).
• Estimated GFR 5.0 mmol/L (or equivalent plasma potassium value) at screening or end-of-run-in visit (Visit 30).
• Current therapy with a mineralocorticoid receptor antagonist (MRA) or sacubitril/valsartan or received an MRA or sacubitril/valsartan within the 4 weeks prior to screening.
• Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma HbA1c ≥9%)
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), high-grade AV block (e.g., Mobitz type II and third-degree AV block in absence of a pacemaker) within 6 months of screening according to investigator's judgement.
• Chronic non-paroxysmal atrial fibrillation.
• Acute myocardial infarction (AMI) or unstable angina, or any history of ischemic or hemorrhagic stroke within 12 months of screening; or any percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) within 12 months of screening
• History of a renal denervation procedure.
• Mid-arm circumference ≥44 cm. The cuff should snugly fit on the arm with out the margins of cuff overhanging arm musculature.
• Patients with history of hospitalisation for hypertensive emergencies characterised by severe hypertension (usually grade 3) associated with funduscopic changes (flame haemorrhages and/or papilloedema), microangiopathy, disseminated intravascular coagulation, encephalopathy, acute aortic dissection, acute myocardial ischaemia, or acute heart failure any time prior to screening or hospitalisation for non-emergent/non-urgent uncontrolled hypertension without target organ damage within 3 months prior to screening
• Receiving more than 4 antihypertensive medications.
• Night shift workers.
• History of presence of any other disease where the life expectancy is less than 3 years.
• History of malignancy of any organ system (other than localized basal or squamous cell carcinoma of the skin or localized prostate cancer), treated or untreated, within the past 3 years, regardless of whether there is evidence of local recurrence or metastases.
• Evidence of hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values exceeding 3x the upper limit of normal (ULN), or bilirubin >1.5 mg