A Research Study to Show the Effect of Aprocitentan in the Treatment of Difficult to Control (Resistant) High Blood Pressure (Hypertension) and Find Out More About Its Safety

Inclusion Criteria:

Screening period:

- Signed and dated ICF prior to any study-mandated procedure;

- Male and female subjects; 18 years (or year of country specific majority) or older;

- Historical documentation in the subject's medical records on uncontrolled BP despite
at least 3 background antihypertensive medications within 1 year before screening
visit;

- Treated with at least 3 antihypertensive therapies of different pharmacological
classes including a diuretic for at least 4 weeks before the screening visit (Visit
1);

- Mean SiSBP ≥ 140 mmHg measured by AOBPM;

- Women of childbearing potential are eligible only if the following applies;

- Negative pregnancy test at screening and at baseline (i.e., before randomization);

- Agreement to undertake pregnancy tests during the study and up to 30 days after
randomized study treatment discontinuation;

- Agreement to use methods of birth control from Screening up to at least 30 days after
randomized study treatment discontinuation.

Run-in period (RI):

- Switched to the standardized background antihypertensive therapy at least 4 weeks
before the first RI visit;

- Mean trough SiSBP ≥ 140 mmHg as measured by AOBPM.

Randomization period:

- Stable dose of the standardized background antihypertensive therapy since start of the
RI period;

- Mean trough SiSBP ≥ 140 mmHg measured by AOBPM.

Exclusion Criteria:

- Apparent/pseudo RHT due to white coat effect, medical inertia, poor therapeutic
adherence, or secondary causes of hypertension (except sleep apnea);

- Confirmed severe hypertension (grade 3) defined as SiSBP≥180 mmHg and/or SiDBP≥110
mmHg as measured by AOBPM at two different timepoints;

- Pregnant or lactating subjects;

- Clinically significant unstable cardiac disease in the opinion of the investigator;

- Severe renal insufficiency;

- Any known factor, disease or clinically relevant medical or surgical conditions that,
in the opinion of the investigator, might put the subject at risk, interfere with
treatment compliance, study conduct or interpretation of the results.