A Multi-center, Double-blind, Double-dummy, Randomized, Placebo- and Active-reference, Parallel Group, Phase 2, Dose-finding Study With ACT-132577 in Subjects With Essential Hypertension (Grade 1 and 2).

AC-080A201

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.

2015-12-14

2017-02-28

2017-04-07

Completed

Early phase I

1659

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 1659, 'type': 'ACTUAL'}}

2022-11-23