No Evidence of QTc Interval Prolongation With Baxdrostat Treatment: Concentration-QTc Modeling Assessment
Abstract
Baxdrostat is a novel, highly potent, selective, competitive inhibitor of human aldosterone synthase currently under development for the treatment of uncontrolled and resistant hypertension and chronic kidney disease. We assessed the risk of QTc-interval prolongation with baxdrostat using concentration-QTc (C-QTc) modeling in healthy adult participants using data from two placebo-controlled Phase 1 studies: a multiple-ascending dose (MAD) study of baxdrostat 0.5-5 mg (N = 56; NCT05500820) and a Phase 1 four-way crossover thorough QT/QTc (TQT) study assessing the pharmacokinetics, pharmacodynamics, safety and tolerability of baxdrostat at supratherapeutic doses of 16 and 32 mg (N = 28; NCT06194032). In the TQT study, 28 participants were randomized to one of four treatment sequences (each n = 7) of baxdrostat 16 mg, baxdrostat 32 mg, placebo and open-label moxifloxacin 400 mg. Digital electrocardiogram and pharmacokinetic data were collected at baseline and up to 48 h post dose. Dependent and independent variables of the pre-specified linear mixed-effect model were placebo-corrected baseline-adjusted ΔΔQTcF and baxdrostat plasma concentrations, respectively. Results were consistent between the two C-QTc modeling analyses. Baxdrostat treatment did not produce QT-interval prolongation, both at concentrations of interest and geometric mean of the maximum observed plasma concentration. Upper bounds of the two-sided 90% confidence interval for the ΔΔQTcF mean estimates were < 10…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 56 participants or records.
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