Purpose

The purpose of the study 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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
SB placebo run-in/randomized with 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 re-randomized (DB-WD) to aprocitentan 25 mg or placebo.
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Aprocitentan 25 mg DB
Part 1: Double-blind, randomized (1:1:1 ratio), parallel-group and placebo-controlled and lasts for 4 weeks. Subjects will receive aprocitentan 25 mg
  • Drug: Aprocitentan 25 mg
    Tablet, oral use
    Other names:
    • ACT-132577
Experimental
Aprocitentan 12.5 mg DB
Part 1: Double-blind, randomized (1:1:1 ratio), parallel-group and placebo-controlled and lasts for 4 weeks. Subjects will receive aprocitentan 12.5 mg
  • Drug: Aprocitentan 12.5 mg
    Tablet, oral use
    Other names:
    • ACT-132577
Placebo Comparator
Placebo DB
Part 1: Double-blind, randomized (1:1:1 ratio), parallel-group and placebo-controlled and lasts for 4 weeks. Subjects will receive placebo
  • Drug: Placebo
    Matching placebo tablet
Experimental
Aprocitentan 25 mg SB
Part 2: Single-blind and single-arm, lasts for 32 weeks. All subjects will receive aprocitentan 25 mg.
  • Drug: Aprocitentan 25 mg
    Tablet, oral use
    Other names:
    • ACT-132577
Experimental
Aprocitentan 25 mg DB-WD
Part 3: Double-blind withdrawal. Subjects will be re-randomized to aprocitentan 25 mg
  • Drug: Aprocitentan 25 mg
    Tablet, oral use
    Other names:
    • ACT-132577
Placebo Comparator
Placebo DB-WD
Part 3: Double-blind withdrawal. Subjects will be re-randomized to placebo.
  • Drug: Placebo
    Matching placebo tablet

Recruiting Locations

University of Alabama at Birmingham Vascular Biology and Hypertension Progra
Birmingham, Alabama 35294

More Details

NCT ID
NCT03541174
Status
Recruiting
Sponsor
Idorsia Pharmaceuticals Ltd.

Study Contact

Clinical Trial Disclosure desk
+18566613721
clinical-trials-diclosure@idorsia.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.