Dose-finding Study With ACT-132577 (Aprocitentan) in Participants With Essential Hypertension

• Status: Completed
• Trial end date: 2017-04-07
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Actelion; Idorsia Pharmaceuticals Ltd.
• Treatments: Endothelin Receptor Antagonists; Lisinopril

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