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
Condition: Resistant Hypertension
MeSH terms: Hypertension
Intervention: Aprocitentan 12.5 mg; Aprocitentan 25 mg; Placebo
Intervention description: Tablet, oral use; Tablet, oral use; Matching placebo tablet
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Study with multiple periods and parts.
Once eligibility is confirmed during screening and the run-in period, the individuals entered the randomized treatment period consisting of 3 parts: Part 1: double-blind (DB), randomized to aprocitentan 12.5 mg, aprocitentan 25 mg or placebo; Part 2 single-blind (SB) aprocitentan 25 mg; Part 3: double-blind withdrawal (DB-WD) re-randomized to aprocitentan 25 mg or placebo.
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 730.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The goal of this clinical trial is to show the blood pressure lowering effect of
      aprocitentan, a new drug, when added to other anti-hypertensive drugs of patients with
      difficult to control (resistant) high blood pressure (hypertension), and to show that blood
      pressure reduction is kept for long period of time.
    

Eligibility criteria:

        Inclusion Criteria:

        Screening period:

          -  Signed and dated informed consent form (ICF) prior to any study-mandated procedure;

          -  Male and female participants; 18 years (or year of country specific majority) or
             older;

          -  Historical documentation in the participant's medical records on uncontrolled blood
             pressure despite at least 3 background antihypertensive medications within 1 year
             before screening visit;

          -  Treated with at least 3 antihypertensive therapies of different pharmacological
             classes for at least 4 weeks before the screening visit (Visit 1);

          -  Mean Sitting Systolic Blood Pressure (SiSBP) greater or equal to 140 mmHg measured by
             Automated Office Blood Pressure Measurement (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 greater than or equal to140 mmHg as measured by AOBPM.

        Randomization period:

          -  Stable dose of the standardized background antihypertensive therapy for at least 1
             week before the end of the RI period;

          -  Mean trough SiSBP greater than or equal to 140 mmHg measured by AOBPM.

        Exclusion Criteria:

          -  Apparent/pseudo Resistant Hypertension (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 greater than or equal to 180
             mmHg and/or Sitting Diastolic Blood Pressure (SiDBP) greater than or equal to 110 mmHg
             as measured by AOBPM at two different timepoints;

          -  Pregnant or lactating participants;

          -  Clinically significant unstable cardiac disease at screening or in the past in the
             opinion of the investigator (exclusion of participants with significant or potential
             unstable cardiac disease);

          -  Severe renal insufficiency;

          -  Any known factor, disease or clinically relevant medical or surgical conditions that,
             in the opinion of the investigator, might put the participant at risk, interfere with
             treatment compliance, study conduct or interpretation of the results.

          -  Treatment with any medication which may affect blood pressure (BP) and/or treatment
             with high dose of loop diuretics (i.e., furosemide greater than 80 mg/day, or
             equivalent dosage of other loop diuretics).