An efficacy, safety, tolerability and dose finding study of XXB750 in resistant hypertension patients

Phase 1

• Conditions: Resistant hypertension; MedDRA version: 21.1Level: LLTClassification code 10081349Term: Resistant hypertensionSystem Organ Class: 10047065 - Vascular disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2021-005738-41-BG
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-11-09
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

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 thiazidelike 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
Runin- 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

Exclusion Criteria

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-ofrun- 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. 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 (partic

Study & Design

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