Subjects whose blood pressure is not under control despite treatment with triple antihypertensive medications, including an angiotensin converting enzyme blocker or angiotensin receptor blocker, a calcium channel blocker, and a thiazide or thiazide-like diuretic will be recruited into the study. Subjects will enter run-in period which lasts for approximately 2 weeks. Subjects whose blood pressure is still not under control at the end of the run-in period despite compliance with triple antihypertensive background treatment (i.e., with mean 24hr systolic blood pressure >135 mmHg) will be randomized to receive one of different dose levels of XXB750 or placebo SC. Overall, a total of approximately 170 participants will be randomized. The study duration is for 20 weeks during which each participant will receive a total of 3 doses of study medication (in addition to 1 dose of study medication during run-in). Ambulatory blood pressure monitoring will occur at baseline, Week 9, and Week 12 (primary endpoint timepoint). Office blood pressure will be measured at each office visit. Home blood pressure will be measured by the participants using provided devices on specified days throughout the study. Participants will be followed to monitor their safety for an additional 8 weeks during which time no active study medication will be given.~Each of the first randomized participants will be assigned to receive one of the lower doses of XXB750 or placebo. A DMC will review the safety and tolerability data of those participants when the first 40 participants have completed at least 5 weeks of the study and, contingent upon DMC's findings of their safety and tolerability experience, the highest XXB750 dose will be introduced in the remaining approximately 130 participants.~The primary clinical question of interest is: Is there a dose-response signal with different doses of XXB750 3 SC injections versus placebo in reducing the mean 24hr SBP at Week 12 from randomization in participants with rHTN, regardless of discontinuation from study treatment, regardless of change in the dose of allowed background antihypertensive medications and regardless of receiving prohibited concomitant medication?
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).