Efficacy and Safety of Baxdrostat in Patients With Uncontrolled Hypertension - HALO

Mar 04, 2023
Font Size
A
A
A
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
CinCor Pharma, Inc.
Date Presented:
03/04/2023
Date Published:
03/04/2023
Original Posted Date:
03/04/2023
References

Contribution To Literature:

The HALO trial showed that baxdrostat 0.5 mg, 1 mg, or 2 mg daily did not significantly reduce BP compared with placebo among patients with uncontrolled HTN.

Description:

The goal of the trial was to compare the safety and efficacy of baxdrostat compared with placebo among patients with uncontrolled hypertension (HTN).

Study Design

In this phase 2 study, patients were randomized in a 1:1:1:1 fashion to either daily dosing of baxdrostat 0.5 mg (n = 63), 1 mg (n = 62), 2 mg (n = 60), or placebo (n = 64).

  • Total screened: 631
  • Total number of enrollees: 249
  • Duration of follow-up: 8 weeks
  • Mean patient age: 60 years
  • Percentage female: 48%

Inclusion criteria:

  • 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
  • Mean seated systolic blood pressure (SBP) ≥140 mm Hg

Exclusion criteria:

  • Mean seated SBP ≥180 mm Hg
  • Body mass index (BMI) >50 kg/m2
  • Estimated glomerular filtration rate <30 mL/min/1.73 m2

Other salient features/characteristics:

  • White: 73%
  • Mean BMI: 32 kg/m2
  • Mean seated BP: 147/83 mm Hg
  • Baseline use of ACEi/ARB: 42%

Principal Findings:

The primary outcome, change in mean seated SBP for baxdrostat 0.5 mg, 1 mg, 2 mg, or placebo, was: -17.0 vs. -16.0 vs. -19.8 vs. -16.6 mm Hg (p > 0.05).

  • Placebo-corrected change in mean seated SBP for baxdrostat 0.5 mg: -0.5 mm Hg (p = 0.83), baxdrostat 1 mg: 0.6 mm Hg (p = 0.79), and baxdrostat 2 mg: -3.2 mm Hg (p = 0.15)

Secondary outcomes for baxdrostat 0.5 mg, 1 mg, 2 mg, or placebo:

  • Change in mean seated diastolic BP (DBP): -5.8 vs. -5.0 vs. -5.4 vs. -5.9 mm Hg (p > 0.05)
  • Patients achieving seated SBP <130 mm Hg at 8 weeks: 57.1% vs. 53.2% vs. 71.7% vs. 56.3% (p > 0.05)
  • Hyperkalemia: 0% vs. 1.6% vs. 5.0% vs. 1.6%
  • All 3 doses reduced serum aldosterone and the highest dose also significantly increased plasma renin activity

Interpretation:

The results of this phase 2 trial indicate that baxdrostat at the doses studied did not significantly reduce SBP or DBP compared with placebo among patients with uncontrolled HTN. A larger than anticipated placebo effect was noted; there was also low adherence with study medication at a few sites. Baxdrostat is an aldosterone synthase inhibitor and reduces aldosterone but not cortisol levels. In BrigHTN (also a phase 2 trial), the highest (2 mg) dose was superior to placebo in reducing BP at 12 weeks among patients with treatment-resistant HTN.

References:

Presented by Dr. Deepak Bhatt at the American College of Cardiology Annual Scientific Session (ACC.23/WCC), New Orleans, LA, March 4, 2023.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Novel Agents, Hypertension

Keywords: ACC23, ACC Annual Scientific Session, Aldosterone, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Angiotensins, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Calcium Channel Blockers, Hyperkalemia, Hypertension, Mineralocorticoid Receptor Antagonists, Nitric Oxide Synthase, Primary Prevention, Renin


< Back to Listings