In the placebo-controlled HALO trial, baxdrostat did not achieve a statistically significant change from baseline in mean seated systolic blood pressure (SBP) in patients with uncontrolled hypertension. The placebo effect in this study was substantial. In a post-hoc analysis, SBP was significantly lowered in patients adherent to the highest dose of 2 mg.
The results of a phase 2 study were highly anticipated, with no new agents to treat uncontrolled hypertension in well over a decade, said Deepak Bhat, MD, MPH at the American College of Cardiology 2023 Annual Scientific Sessions.1 Baxdrostat is a highly selective aldosterone synthase inhibitor. Its efficacy and safety were evaluated in the randomized, double-blind, placebo-controlled, multicenter, phase 2 HALO trial (NCT05137002). Participants had to be on a stable regimen of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), an ACEi/ARB plus a thiazide diuretic, or an ACEi/ARB plus a calcium channel blocker, and have a mean seated SBP of 140 mmHg or greater. The primary endpoint was change from baseline in mean seated SBP after 8 weeks of treatment. A total of 249 patients were randomized 1:1:1:1 to baxdrostat 0.5 mg, 1 mg, 2 mg, or placebo; 227 completed the trial.
The primary endpoint was not met with any baxdrostat dose. SBP changes were -16.6 mmHg in the placebo group, and -17.0, -16.0, and -19.8 mmHg in the 0.5 mg, 1 mg, and 2 mg groups, respectively. Changes in placebo-corrected SBP for the 0.5, 1, and 2 mg groups were -0.5 mmHg (P=0.83), 0.6 mmHg (P=0.79), and -3.2 mmHg (P=0.15). Similarly, none of the baxdrostat doses were associated with a significant difference in placebo-corrected diastolic blood pressure (DBP), which was a secondary endpoint. Change in DBP at 8 weeks did not significantly differ either; nor did the percentage of patients achieving a seated SBP response less than 130 mmHg at 8 weeks. Baxdrostat significantly reduced serum aldosterone levels at all doses. The treatment was well tolerated.
Dr. Bhat explained that a post-hoc analysis was done in patients who were adherent to the highest baxdrostat dose of 2 mg. The reason was that 20 of 54 (36%) patients in the 2 mg arm who completed 8 weeks of treatment had baxdrostat levels less than 0.2 ng/dL, indicating non-adherence (despite dosing records by pill count showing >95% adherence in all groups). This subgroup analysis suggested a placebo-corrected SBP reduction of 7.9 mmHg in patients adherent to baxdrostat 2 mg.
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