No Influence of Asundexian on Cardiac Repolarization.

Inhibition of activated factor XI reduces thrombogenesis while maintaining physiological hemostasis, with the expectation of reduced bleeding risk compared with standard of care in the clinical setting. Asundexian (BAY 2433334), an activated factor XI inhibitor, is in clinical development for the prevention of thromboembolic events. The effect of asundexian and its plasma metabolite M10 on cardiac repolarization and potential interactions with the hNav1.

Results From Drug-Drug Interaction Studies In Vitro and In Vivo Investigating the Inhibitory Effect of Finerenone on the Drug Transporters BCRP, OATP1B1, and OATP1B3.

Background And Objectives: In vitro and in vivo studies were performed with the novel, selective, nonsteroidal mineralocorticoid receptor antagonist finerenone to assess the relevance of inhibitory effects on the transporters breast cancer resistance protein (BCRP), organic anion transporting polypeptide 1B1 (OATP1B1), and OATP1B3. These transporters are involved in the disposition of a number of drugs, including statins. Statins are also a frequent comedication in patients receiving finerenone.

Results From Phase I Studies Investigating the Dose Linearity of Finerenone Tablets and the Influence of Food or pH-Modifying Comedications on its Pharmacokinetics in Healthy Male Volunteers.

Background And Objectives: Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that reduces the risk of adverse kidney and cardiovascular outcomes in patients with chronic kidney disease associated with type 2 diabetes mellitus. Clinical phase I studies with finerenone were carried out to assess its pharmacokinetics and the influence of common covariables on its absorption after oral administration.

Methods: Three crossover studies in healthy male volunteers with single-dose administration of finerenone investigated the dose linearity of a film-coated tablet (1.

Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.

Purpose: To characterize the safety, pharmacodynamics, and pharmacokinetics (PK) of vericiguat in healthy males.

Methods: Six phase I studies were conducted in European, Chinese, and Japanese males. Subjects received oral vericiguat as a single dose (0.

Pharmacodynamic and Pharmacokinetic Interaction Profile of Vericiguat: Results from Three Randomized Phase I Studies in Healthy Volunteers.

Background: Vericiguat, a direct stimulator of soluble guanylate cyclase, has been developed as a first-in-class therapy for symptomatic chronic heart failure (HF) and ejection fraction < 45%.

Methods: Safety, pharmacodynamic (PD), and pharmacokinetic (PK) interactions between vericiguat and drugs used in HF (sacubitril/valsartan [SV] and aspirin [acetylsalicylic acid]) or with a narrow therapeutic index (warfarin) were evaluated in three phase I studies.

Results: Vericiguat 15 mg (single dose [SD]) had no effect on bleeding time or platelet aggregation when coadministered with aspirin 1000 mg versus aspirin alone: estimated differences in least squares means 2.

The effects of vilaprisan on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive-A randomized controlled trial.

Aims: The primary objective was to explore whether the suppression of ovarian activity induced by a combined oral contraceptive (COC) is influenced by the simultaneous intake of the selective progesterone receptor modulator (SPRM) vilaprisan (VPR).

Methods: In this exploratory randomized, double-blind, parallel-group study, 71 healthy premenopausal women were randomized (1:1) to receive either 2 mg/d VPR or placebo for 3 months. Concomitantly, a COC (0.

Pharmacokinetics and Safety of the Novel Selective Progesterone Receptor Modulator Vilaprisan in Participants With Renal Impairment.

This open label, parallel-group study investigated the pharmacokinetics and safety of a single oral 2-mg dose of the novel selective progesterone receptor modulator vilaprisan in participants with impaired renal function compared with age, weight, sex, and race matched controls with normal renal function. Systemic exposure (area under the plasma concentration-time curve [AUC]) and maximum observed concentrations (C ) were compared among 9 participants with moderate renal impairment and matched controls by ANOVA. An additional 4 participants, each with severe renal impairment or normal renal function, contributed to a linear regression analysis exploring any monotone relationship between individual variables and the estimated glomerular filtration rate.

Results from Drug-Drug Interaction Studies In Vitro and In Vivo Investigating the Effect of Finerenone on the Pharmacokinetics of Comedications.

Background And Objectives: In vivo studies were performed with the novel, selective, non-steroidal mineralocorticoid receptor antagonist finerenone to assess the relevance of inductive and/or inhibitory effects on cytochrome P450 (CYP) enzymes observed in vitro.

Methods: CYP isoenzyme-specific substrates were incubated in vitro with finerenone or its metabolites to investigate reversible and irreversible inhibitory as well as inductive potential. Three crossover studies in healthy male volunteers investigated the effects of finerenone (20 mg orally) on the pharmacokinetics of the index substrates midazolam (CYP3A4, n = 30), repaglinide (CYP2C8, n = 28) and warfarin (CYP2C9, n = 24).

Pharmacokinetics of the Novel, Selective, Non-steroidal Mineralocorticoid Receptor Antagonist Finerenone in Healthy Volunteers: Results from an Absolute Bioavailability Study and Drug-Drug Interaction Studies In Vitro and In Vivo.

Background And Objectives: Finerenone is a selective, non-steroidal mineralocorticoid receptor antagonist. In vivo and in vitro studies were performed to assess absolute bioavailability of finerenone, the effect of metabolic enzyme inhibitors on the pharmacokinetics of finerenone and its metabolites, the quantitative contribution of the involved enzymes cytochrome P450 (CYP) 3A4 and CYP2C8 and the relevance of gut wall versus liver metabolism.

Methods: The pharmacokinetics, safety and tolerability of finerenone (1.