An efficacy, safety, tolerability and dose finding study of XXB750 in resistant hypertension patients
- Conditions
- Resistant hypertensionTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2021-005738-41-NL
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 170
1. Male and female participants who are = 18 years old.
2. Signed informed consent prior to participation in the study.
3. Apparent rHTN at screening (Visit 1) defined as uncontrolled BP with an office msSBP = 140 mmHg despite treatment with stable (i.e., unchanged for =4 weeks), optimal or maximally tolerated doses of three or four antihypertensive drugs of different classes, Including an ACEI/ARB, a long-acting dihydropyridine CCB, and a thiazide or thiazide-like diuretic. Participant with documented intolerance to any doses of CCBs may be eligible if receiving another class of antihypertensive medication at an optimal or maximally tolerated dose (referred to as triple background antihypertensive therapy. An optimal dose is defined as the highest dose taking in to account participant's documented comorbidities and tolerability per investigator's clinical judgement.
4. Mean 24hr SBP =135 mmHg (measured by ABPM) at the end-of Run-in-Visit (Visit 30) on treatment with optimal or maximally tolerated doses of an ACEI/ARB, a long-acting dihydropyridine CCB, (or a suitable alternative in case of intolerance per inclusion criterion above), and a thiazide or thiazide-like diuretic.
Additional inclusion criteria are described in the clinical study protocol.
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 170
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Subjects with the following blood pressures at the specified time points are not eligible to participate in the study
a.Office msSBP <140 mmHg at Visit 20 OR
b.Office msSBP =180 mmHg or office msDBP =110 mmHg at the end-of-run-in visit (Visit 30) OR
c.24h mean SBP >170 mmHg or 24h mean DBP >105mmHg measured by ABPM at the end of the run-in (Visit 30).
2. Known history of secondary hypertension (moderate-to-severe obstructive sleep apnea without receiving CPAP therapy (either face mask or nasal device), renovascular hypertension, primary aldosteronism, pheochromocytoma, Cushing syndrome, aortic coarctation or other cause of secondary hypertension).
3. Estimated GFR <30 mL/min/1.73m2 using CKD-Epi equation at screening (Visit 1) or at end-of-run-in visit (Visit 30).
4. Serum potassium >5.0 mmol/L (or equivalent plasma potassium value) at screening or end-of-run-in visit (Visit 30).
5. 5.Current therapy with a mineralocorticoid receptor antagonist (MRA) or sacubitril/valsartan or received an MRA or sacubitril/valsartan within the 4 weeks prior to screening.
6. Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma HbA1c =9%)
7. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), high-grade AV block (e.g., Mobitz type II and third-degree AV block in absence of a pacemaker) within 6 months of screening according to investigator's judgement.
8. Chronic non-paroxysmal atrial fibrillation
9. Acute myocardial infarction (AMI) or unstable angina, or any history of ischemic or hemorrhagic stroke within 12 months of screening; or any percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) within 12 months of screening
10. History of a renal denervation procedure.
11. Mid-arm circumference = 44 cm. The cuff should snugly fit on the arm without the margins of cuff overhanging arm musculature.
12.Patients with history of hospitalisation for hypertensive emergencies characterised by severe hypertension (usually grade 3) associated with funduscopic changes (flame haemorrhages and/or papilloedema), microangiopathy, disseminated intravascular coagulation, encephalopathy, acute aortic dissection, acute myocardial ischaemia, or acute heart failure any time prior to screening or hospitalisation for non-emergent/non-urgent uncontrolled hypertension without target organ damage within 3 months prior to screening
13. Receiving more than 4 antihypertensive medications.
14. Night shift workers.
15. History of presence of any other disease where the life expectancy is less than 3 years.
16. History of malignancy of any organ system (other than localized basal or squamous cell carcinoma of the skin or localized prostate cancer), treated or untreated, within the past 3 years, regardless of whether there is evidence of local recurrence or metastases.
17. Evidence of hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values exceeding 3x the upper limit of normal (ULN), or bilirubin >1.5 mg/dl at Visit 1.
18. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
19. History of drug abuse or alcohol dependency.
20. Lacking the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, a participant that would be unlikely or unable to comply with study protocol.
21. Concurrent enrollment in any other investigational drug or device trial (
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy and dose-response relationship of different doses of XXB750 SC compared to placebo in reducing the mean 24hr ambulatory systolic blood pressure (mean 24hr SBP) from baseline at Week 12.;Secondary Objective: To evaluate the treatment effect of the highest XXB750 dose versus placebo in reducing the mean 24hr SBP from baseline to Week 12.<br><br>To evaluate the treatment effect of the highest XXB750 dose versus<br>placebo in the dosing interval average of ambulatory SBP as assessed by average of mean 24hr SBP measured at week 9 and week 12<br><br>To evaluate the proportions of participants achieving ambulatory BP<br>control (i.e., mean 24hr SBP < 130 mmHg and mean 24hr DBP < 80<br>mmHg) with respect to the dose-response relationship of the four<br>XXB750 dose level groups compared to placebo at week 12.<br><br>;Primary end point(s): Change from baseline in mean 24hr SBP at Week 12 ;Timepoint(s) of evaluation of this end point: Week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Change from baseline in mean 24hr SBP at Week 12<br>Nocturnal SBP dipping expressed as (nighttime mean SBP/daytime mean SBP) at Week 12 <br>The proportions of participants achieving blood pressure control defined as mean 24hr SBP <130 mmHg and mean 24hr DBP <80 mmHg at Week 12<br>Adverse events, safety laboratory parameters, and vital signs through end of treatment/study (EOT/EOS)<br>;Timepoint(s) of evaluation of this end point: Week 12