Hypertension
Conditions
Interventions
Product Name: Aprocitentan
Product Code: ACT-132577
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Aprocitentan
Current Sp
Sponsors
Idorsia Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Screening Visit: - Signed and dated informed consent prior to any study-mandated procedure, - Adult male and female subjects, - Prior treatment with at least 2 anti-hypertensive medications, at optimal or best tolerated dose, of different pharmacological classes, including a diuretic, - Subjects with uncontrolled blood pressure (mean sitting systolic blood pressure of 140 mmHg or greater) and chronic kidney disease stage 3 or 4 (estimated Glomerular Filtration Rate, eGFR, of at least 15 and below 60 mL/min/1.73m2 using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation.), - Women of childbearing potential (WOCBP) are eligible only if the following applies: --Negative pregnancy test at the screening visit and at baseline (i.e., end of Run-in period). -- Agree to undertake pregnancy tests during the study and up to 30 days after randomized study treatment discontinuation. -- Agree to use highly-effective methods of contraception as described up to at least 30 days after randomized study treatment discontinuation. Run-in period criteria: - Mean trough sitting systolic blood pressure of 140 mmHg or higher measured by automated office blood pressure measurement (AOBPM). Randomization (Baseline) criteria (end of the 2 week run-in period): - Mean trough sitting systolic blood pressure of 140 mmHg or higher measured by AOBPM, - Stable background anti-hypertensive therapy (including a diuretic) since the start of the run-in period, - Estimated glomerular filtration rate (eGFR) equal or above 15 to less than 60 mL/min/1.73 m2, - Subject is at least 80% compliant with study treatment (tablet count) during the run-in period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 105 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 95
Exclusion criteria
Exclusion criteria: - Mean sitting systolic blood pressure above 170 mmHg measured by automated office blood pressure measurement (AOBPM), - Mean sitting diastolic blood pressure above 105 mmHg measured by AOBPM, - Change in renal function requiring hospitalization, - Documented eGFR decline of more than 20% in the 3 months prior to the screening visit, - Dialysis in the 3 months before the screening visit, - Planned dialysis or kidney transplant during the course of this study, - Nephrotic syndrome defined as urine albumin-to-creatinine ratio above 3000 mg/g, - Known and documented chronic heart failure.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to demonstrate the blood pressure (BP) lowering effect of aprocitentan when added to background antihypertensive therapy in subjects with uncontrolled BP and chronic kidney disease (CKD) stage 3 or 4 after 4 weeks of double-blind (DB) treatment.; Secondary Objective: The secondary objectives are to evaluate: - the effect of aprocitentan on urine albumin-to-creatinine ratio (UACR) after 4 weeks of DB treatment in a subset of study population; i.e., in subjects with a UACR greater than 30 mg/g at baseline; - the safety and tolerability of aprocitentan in this study population during 12 weeks of the randomized treatment period. ; Primary end point(s): Change from Baseline to Week 4 of double-blind (DB) treatment in mean trough sitting systolic blood pressure measured by automated office blood pressure measurement. ;Timepoint(s) of evaluation of this end point: 4 Weeks (starting at the baseline visit, i.e. last assessment before start of the double-blind treatment to the end of the double-blind treatment part). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline to Week 4 of double-blind (DB) treatment in mean trough sitting diastolic blood pressure measured by automated office blood pressure measurement. -Ratio to baseline of urine albumin-to-creatinine ratio (UACR) at Week 4 of the DB treatment (evaluated in subjects with a UACR above 30 mg/g at baseline). ;Timepoint(s) of evaluation of this end point: 4 Weeks (starting at the baseline visit, i.e. last assessment before start of the double-blind treatment to the end of the double-blind part). | — |
Countries
Australia, Belgium, Canada, Czech Republic, France, Hungary, Korea, Republic of, Latvia, Lithuania, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Disclosure Desk
Idorsia Pharmaceuticals Ltd
Outcome results
None listed