Dose-finding Study With ACT-132577 (Aprocitentan) in Participants With Essential Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Aprocitentan 5 mg; Aprocitentan 10 mg; Aprocitentan 25 mg; Aprocitentan 50 mg; Lisinopril 20 mg; Placebo
Intervention description: One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.; Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.; One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.; One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.; One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan; One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.
Intervention MeSH terms: Lisinopril
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1659.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The main objective will be to evaluate the dose-response of ACT-132577 (aprocitentan) on
      diastolic blood pressure (DBP) in participants with grade 1 or 2 essential hypertension.

      Secondary objectives will be to evaluate the dose-response of ACT-132577 on: systolic blood
      pressure (SBP); control and response rate of blood pressure; 24-hour ambulatory blood
      pressure monitoring (ABPM) and to evaluate the safety and tolerability of a once daily oral
      regimen of 4 doses of ACT-132577.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent prior to any study-mandated procedure

          -  No contra-indication to stop (according to label) anti-hypertensive treatment(s) at
             screening

          -  Mild-to-moderate essential hypertension with or without ongoing anti-hypertensive
             treatment(s):

             -- Mean (of 5 measurements) sitting diastolic blood pressure (SiDBP) ≥ 90 to < 110
             mmHg measured by office blood pressure measurements (OBPM).

          -  Women of childbearing potential must have a negative pregnancy test and use of
             reliable methods of contraception

        Exclusion Criteria:

          -  Severe hypertension (grade 3): mean sitting systolic/diastolic BP (SiSBP/SiDBP;
             measured by OBPM) ≥ 180/110 mmHg, respectively.

          -  Secondary hypertension

          -  Known hypertensive retinopathy greater than Keith-Wagener Grade 2

          -  Myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary
             artery bypass graft within 12 months prior to randomization

          -  Unstable angina within 6 months prior to randomization

          -  Heart failure New York Heart Association class III and IV

          -  Valvular defects (such as severe aortic or mitral valve disease) and/or
             hemodynamically relevant rhythm disturbances

          -  Clinical evidence of cerebrovascular insufficiency or a cerebrovascular accident
             within 6 months prior to randomization.

          -  Subjects working night shifts

          -  Body mass index < 20 kg/m2 or > 40 kg/m2

          -  Treatment with any medication which may affect BP (e.g., treatment of psychiatric
             diseases, ophthalmic preparations)

          -  Treatment with strong cytochrome P450 3A4 (CYP3A4) isoenzyme inhibitors or inducers

          -  Treatment with guanethidine and/or mineralocorticoid receptor antagonists within 1
             month prior to Screening (Visit 1)

          -  Treatment with another investigational treatment within 1 month prior to Screening
             (Visit 1)

          -  Any circumstances or conditions, which, in the opinion of the investigator, may affect
             full participation in the study or compliance with the protocol