A Research Study to Show Aprocitentan is Efficacious and Safe to Treat Patients With Uncontrolled Blood Pressure and Chronic Kidney Disease.

Study Overview
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Brief Summary
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The purpose of this research study is to show the blood pressure lowering effect of aprocitentan, a new drug, when added to the background antihypertensive therapy in patients with uncontrolled blood pressure and chronic kidney disease (CKD) stage 3 or 4. Participation in the research study will last up to 21 weeks (about 5 months).

Official Title
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Multi-center, Blinded, Randomized Study With Aprocitentan in Subjects With Uncontrolled Blood Pressure and Chronic Kidney Disease Stage 3 or 4.

Conditions
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Hypertension, Renal Insufficiency, Chronic

Intervention / Treatment
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* Drug: Aprocitentan 25 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior treatment with at least 2 anti-hypertensive medications, at optimal or best tolerated dose, of different pharmacological classes, including a diuretic, Participants 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 of at least 15 and below 60 mL/min/1.73m2 using the Chronic Kidney Disease-Epidemiology equation), Women of childbearing potential 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 up to at least 30 days after study treatment discontinuation. 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 greater 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All participants will get the active drug, aprocitentan 25 mg, for at least 8 weeks. All participants will receive placebo for 2 weeks. During a certain period of the study, participants will receive aprocitentan 25 mg or placebo for 4 weeks.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aprocitentan 25 mg<br> | Drug: Aprocitentan 25 mg<br>* Tablet, oral use once daily<br>* Other names: ACT-132577;|
| Experimental: Placebo<br> | Drug: Placebo<br>* Matching placebo tablet, oral use once daily<br>|
| Experimental: Aprocitentan 25 mg or Placebo<br> | Drug: Aprocitentan 25 mg<br>* Tablet, oral use once daily<br>* Other names: ACT-132577;Drug: Placebo<br>* Matching placebo tablet, oral use once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 4 of double-blind treatment in mean trough sitting systolic blood pressure measured by automated office blood pressure measurement. |  | From baseline to Week 4 after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 4 of double-blind treatment in mean trough sitting diastolic blood pressure measured by automated office blood pressure measurement. |  | From baseline to Week 4 after treatment initiation | 
| Ratio to baseline of urine albumin-to-creatinine ratio (UACR) at Week 4 | Evaluated in the subgroup of participants with a UACR greater than 30 mg/g at baseline. | From baseline to Week 4 after treatment initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic kidney disease