A research study to find out if aprocitentan is efficacious and safe to treat difficult to control (resistant) high blood pressure (hypertension)

Phase 1

• Conditions: Resistant Hypertension; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]; MedDRA version: 20.0 Level: LLT Classification code 10020783 Term: Hypertension not adequately controlled System Organ Class: 100000004866

• Registration Number: EUCTR2017-004393-33-FR
• Lead Sponsor: Idorsia Pharmaceuticals Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-04-18
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 600

Inclusion Criteria

- Screening criteria:
Signed and dated ICF prior to any study-mandated procedure;
Male and female subjects; 18 years (or year of country specific majority) or older;
Historical documentation in the subject’s medical records on uncontrolled BP despite at least 3 background antihypertensive medications within 1 year before screening visit;
Treated with at least 3 antihypertensive therapies of different pharmacological classes including a diuretic for at least 4 weeks before the screening visit (Visit 1);
Mean SiSBP = 140 mmHg measured by AOBPM;
Women of childbearing potential are eligible only if the following applies;
Negative pregnancy test at screening and at baseline (i.e., end of RI period);
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 entry criteria:
Switched to the standardized background antihypertensive therapy at least 4 weeks before the first RI visit;
Mean trough SiSBP = 140 mmHg measured by AOBPM.

- Randomization criteria:
Stable dose of the standardized background antihypertensive therapy since the start of the RI period;
Mean trough SiSBP = 140 mmHg measured by AOBPM.
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

Exclusion Criteria

- Apparent/pseudo 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 = 180 mmHg and/or SiDBP = 110 mmHg as measured by AOBPM at two different time points.;
- Pregnant or lactating subjects;
- Clinically significant unstable cardiac disease in the opinion of the investigator;
- Severe renal insufficiency;
- N-terminal pro-brain natriuretic peptide (NT-proBNP) = 200 pg/mL;
- Any known factor, disease or clinically relevant medical or surgical conditions that, in the opinion of the investigator, might put the subject at risk, interfere with treatment compliance, study conduct or interpretation of the results

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To demonstrate the blood pressure (BP) lowering effect of aprocitentan when added to standard of care in true resistant hypertension (RHT) subjects.;<br> Secondary Objective: - To demonstrate that the effect of aprocitentan on BP is durable when added to standard of care in true RHT subjects.<br><br> - To evaluate the long-term safety and tolerability of aprocitentan in true RHT subjects during 48 weeks of treatment.<br> ;Primary end point(s): - Change from baseline to Week 4 of double-blind (DB) treatment in mean trough SiSBP measured by AOBPM.;Timepoint(s) of evaluation of this end point: From baseline to Week 4 after treatment initiation.

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): - Change from Week 36 (i.e., start of double-blind withdrawal [DB-WD]) to Week 40 in mean trough SiSBP measured by AOBPM<br> - Change from baseline to Week 4 of DB treatment in trough Sitting Diastolic BP (SiDBP) measured by AOBPM;<br> - Changes from baseline to Week 4 of DB treatment in 24-h mean SBP and DBP measured by ABPM;<br> - Change from Week 36 to Week 40 of DB-WD treatment in mean trough SiDBP measured by AOBPM;<br> - Changes from Week 36 to Week 40 of DB-WD treatment in 24-h mean SBP and DBP measured by ABPM.<br> ;Timepoint(s) of evaluation of this end point: From baseline to week 4, or from week 36 to week 40.