A Research Study to Show the Effect of Aprocitentan in the Treatment of Difficult to Control (Resistant) High Blood Pressure (Hypertension) and Find Out More About Its Safety
Purpose
The goal of this clinical trial 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
- Resistant Hypertension
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
Screening period: - Signed and dated informed consent form (ICF) prior to any study-mandated procedure; - Male and female participants; 18 years (or year of country specific majority) or older; - Historical documentation in the participant's medical records on uncontrolled blood pressure despite at least 3 background antihypertensive medications within 1 year before screening visit; - Treated with at least 3 antihypertensive therapies of different pharmacological classes for at least 4 weeks before the screening visit (Visit 1); - Mean Sitting Systolic Blood Pressure (SiSBP) greater or equal to 140 mmHg measured by Automated Office Blood Pressure Measurement (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 greater than or equal to140 mmHg as measured by AOBPM. Randomization period: - Stable dose of the standardized background antihypertensive therapy for at least 1 week before the end of the RI period; - Mean trough SiSBP greater than or equal to 140 mmHg measured by AOBPM.
Exclusion Criteria
- Apparent/pseudo Resistant Hypertension (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 greater than or equal to 180 mmHg and/or Sitting Diastolic Blood Pressure (SiDBP) greater than or equal to 110 mmHg as measured by AOBPM at two different timepoints; - Pregnant or lactating participants; - Clinically significant unstable cardiac disease at screening or in the past in the opinion of the investigator (exclusion of participants with significant or potential unstable cardiac disease); - Severe renal insufficiency; - Any known factor, disease or clinically relevant medical or surgical conditions that, in the opinion of the investigator, might put the participant at risk, interfere with treatment compliance, study conduct or interpretation of the results. - Treatment with any medication which may affect blood pressure (BP) and/or treatment with high dose of loop diuretics (i.e., furosemide greater than 80 mg/day, or equivalent dosage of other loop diuretics).
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Study with multiple periods and parts. Once eligibility is confirmed during screening and the run-in period, the individuals entered the randomized treatment period consisting of 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 withdrawal (DB-WD) re-randomized to aprocitentan 25 mg or placebo.
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Aprocitentan 25 mg in Part 1 (double-blind) |
Participants will receive aprocitentan 25 mg, orally, once daily in the morning for 4 weeks. |
|
|
Experimental Aprocitentan 12.5 mg in Part 1 (double-blind) |
Participants will receive aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks. |
|
|
Placebo Comparator Placebo in Part 1 (double-blind) |
Participants will receive placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks. |
|
|
Experimental Aprocitentan 25 mg in Part 2 (single-blind, single arm) |
After 4-weeks in the double-blind randomized part (Part 1), participants will received 25 mg aprocitentan, orally, once daily in the morning for 32 weeks. |
|
|
Experimental Aprocitentan 25 mg in Part 3 (double-blind withdrawal) |
After 32-weeks in the single-blind, single-arm part (Part 2), participants will be re-randomized and receive aprocitentan 25 mg, orally, once daily in the morning for 12 weeks. |
|
|
Placebo Comparator Placebo in Part 3 (double-blind withdrawal) |
After 32-weeks in the single-blind, single-arm part (Part 2), participants will be re-randomized and receive placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks. |
|
More Details
- Status
- Completed
- Sponsor
- Idorsia Pharmaceuticals Ltd.
Study Contact
Detailed Description
Participation in the study will be up to 68 weeks. The study has 4 periods: 1. Screening period 2. Placebo run-in period 3. Randomized treatment period 4. Safety follow-up period The screening period lasts between 4 and 12 weeks. It starts at the screening visit with the signing of the informed consent form (ICF) and ends the day before the participant enters the run-in period. At least 4 weeks before the start of the run-in period, the background antihypertensive medication (except beta-blockers) of participants with a diagnosis of true resistant hypertension and having a mean trough sitting systolic blood pressure of equal to or greater than 140 mmHg measured by automated AOBPM will be standardized by switching to a fixed combination of a calcium channel blocker (amlodipine), an angiotensin receptor blocker (valsartan) and a diuretic (hydrochlorothiazide). In case a beta-blocker is used as one of the background antihypertensive medications or for any other indication, this can be kept, with the provision that it has been initiated and the dose kept stable for at least 4 weeks prior to the screening visit and the dose kept stable until the end-of-treatment. Following the screening period this study has a run-in period of 4 weeks. During this period, placebo will be administered in order to exclude potential placebo responders. Following the run-in period eligible participants will enter the randomized treatment period. This period lasts for 48 weeks. It starts at randomization (i.e., Day 1 of the double-blind part) and ends at the end-of-treatment visit (i.e., at the end of the double-blind withdrawal part). The randomized treatment period consists of 3 parts: Part 1 is double-blind, randomized, parallel-group and placebo-controlled and lasts 4 weeks. Part 2 is single-blind and single-arm and lasts for 32 weeks. Part 3 is a double-blind withdrawal, randomized, parallel-group and placebo-controlled and lasts for 12 weeks. End-of treatment is at Week 48 (i.e., end of the double-blind withdrawal part). The safety follow-up starts on the day after the last dose of study treatment and ends 30 to 33 days after the last dose of study treatment.