An Efficacy, Safety, Tolerability and Dose Finding Study of XXB750 in Resistant Hypertension Patients.
A Multi-center, Randomized, Double-blind, Parallel-group, 20-week Dose-finding Study to Evaluate Efficacy, Safety, and Tolerability of XXB750 in Patients With Resistant Hypertension
ClinicalTrials.gov Identifier: NCT05562934
Novartis Reference Number: CXXB750B12201
Last Update: Mar 28, 2023
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.
The purpose of this 20-week randomized double-blind study in patients with resistant hypertension (rHTN) is to evaluate the efficacy, safety, and tolerability, of different doses of XXB750 administered as subcutaneous (SC) injections, compared to placebo. Since all study participants will be patients with rHTN, all study treatments will be given on top of maximally tolerated background antihypertensive therapy recommended by international guidelines for treatment of HTN (i.e., a thiazide or a thiazide-like diuretic, an angiotensin converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), and a long-acting dihydropyridine calcium channel blocker (CCB).
Male and female participants who are ≥ 18 years old.
Signed informed consent prior to participation in the study.
Apparent rHTN at screening (Visit 1) defined as uncontrolled BP with an office msSBP ≥ 145 mmHg despite treatment with stable (i.e., unchanged for ≥4 weeks), maximally tolerated doses of three antihypertensive drugs of different classes, specifically an ACEI/ARB, a long-acting dihydropyridine CCB, and a thiazide or thiazide-like diuretic. Refer to Section 10.8 for minimum required doses of some commonly prescribed drugs in those classes.
Mean 24hr SBP ≥135 mmHg (measured by ABPM) at the end-of Run-in-Visit (Visit 30) on treatment with maximally tolerated doses of an ACEI/ARB, a long-acting dihydropyridine CCB, and a thiazide or thiazide-like diuretic.
Office msSBP <140 mmHg at Visit 20 or Visit 30 OR office msSBP ≥180 mmHg or office msDBP ≥110 mmHg at the end-of-run-in visit (Visit 30) OR 24h mean SBP >170 mmHg or 24h mean DBP >105mmHg measured by ABPM at the end of the run-in (Visit 30).
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).
Estimated GFR <30 mL/min/1.73m2 using CKD-Epi equation at screening (Visit 1) or at end-of-run-in visit (Visit 30).
Serum potassium >5.0 mmol/L (or equivalent plasma potassium value) at screening or end-of-run-in visit (Visit 30).
Current therapy with a mineralocorticoid receptor antagonist (MRA) or received an MRA within the 4 weeks prior to screening.
Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma HbA1c ≥9%)
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.
Chronic non-paroxysmal atrial fibrillation.
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
History of a renal denervation procedure.
Mid-arm circumference ≥42 cm.
Hospitalization for hypertensive emergency / crisis within the 12 months prior to screening.
Received any antihypertensive medication other than the CCB, ACEI/ARB, and thiazide/thiazide-like diuretic components of the triple background antihypertensive therapy, including sacubitril/valsartan within the 4 weeks before screening (Visit 1). Participants receiving beta blockers and prostate-specific alpha blockers (e.g., tamsulosin) are allowed in the study only if those medications are being used for non-hypertension indications and benign prostatic hypertrophy, respectively.
Night shift workers.
History of presence of any other disease where the life expectancy is less than 3 years.
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.
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.
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
History of drug abuse or alcohol dependency.
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.
Concurrent enrollment in any other investigational drug or device trial (participation in non-interventional registries is acceptable).
Requiring prolonged/regular use of NSAIDs or other prohibited medications during of the study (i.e., required use for longer than 1 week).
Pregnant, nursing or planning to become pregnant (documented negative pregnancy test required within a maximum of 7 days prior to enrollment of all women of childbearing potential). Documentation of highly effective contraception is also required for women of childbearing potential (see below).
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 3 months after stopping medication. Highly effective contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
Use of oral, (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms). Women are considered not of childbearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child bearing potential.
If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF.