Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs
Disease area: Airway diseases

Abstract

Human neutrophil elastase (HNE) is a key mediator of tissue remodeling and inflammation. An excess of HNE activity has been implicated in the pathogenesis of inflammatory pulmonary diseases, e.g. bronchiectasis (BE), COPD, and pulmonary hypertension. HNE inhibitors could potentially restore the protease/anti-protease balance in these diseases providing a new therapeutic target.BAY 85-8501 is a novel, selective and reversible HNE inhibitor with activity in the picomolar concentration range, which reveals target inhibition in the lung and ameliorates pulmonary inflammation in preclinical models.This First-in-Man study evaluated BAY 85-8501 in a Single-Dose-Escalation (SDE) design with 0.05, 0.1, 0.2, 0.5 or 1.0 mg as oral liquid formulation in 37 healthy male subjects (27 active, 10 placebo).The single dose treatments were safe and well tolerated without serious or severe adverse events and without any hints for mode of action or drug substance related adverse effects. All clinical safety parameters (BP, HR, ECG) and clinical laboratory parameters were in the normal range for single doses up to 1 mg.Drug absorption was fast, max. concentration (C) reached after 1 h, mean drug half-life was up to 145 - 175 h, allowing once daily dosing. Max. C and Area under Curve (0-24) increased in a dose-proportional way. Renal elimination of the unchanged drug is a minor pathway of elimination ( 4%).SDE up to 1 mg BAY 85-8501 was safe and well tolerated with pharmacokinetics that allow once daily dosing. Drug candidate is adequate for further clinical evaluation in studies in chronic anti-inflammatory treatment of lung diseases.

Rating:

Share or cite this content

Citations should be made in the following way:
J. Nagelschmitz, M. Becka, D. Kaufel, S. Schwers, F. von Nussbaum, V. Li, G. Wensing (Wuppertal, Germany). The novel elastase inhibitor BAY 85-8501: First-in-man study to evaluate safety, tolerability and pharmacokinetics in healthy male subjects. Eur Respir J 2014; 44: Suppl. 58, 1510

Member's Comments

No comment yet.

Related content which might interest you: The novel elastase inhibitor BAY 85-8501: Bioavailability and Food effect study to evaluate pharmacokinetics of tablet formulations Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs Year: 2014 Safety, tolerability and pharmacokinetics of a new inhaled once-daily phosphodiesterase (PDE) 4 inhibitor in healthy volunteers Source: Annual Congress 2013 –Novel drugs and biomarkers in respiratory medicine Year: 2013 Safety, tolerability and pharmacokinetics of CHF 6001, a novel selective inhaled PDE4 inhibitor, in healthy volunteers Source: International Congress 2016 – Preclinical pharmacology: drug targets and mechanisms of action Year: 2016 The novel elastase inhibitor BAY 85-8501 provides a new approach in the treatment of pulmonary diseases Source: International Congress 2014 – New drugs for asthma, COPD and pulmonary fibrosis Year: 2014 Safety, tolerability and pharmacokinetics of AZD9668, an oral neutrophil elastase inhibitor, in healthy subjects and patients with COPD Source: Annual Congress 2010 - New treatments for asthma and COPD Year: 2010 Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single (SD) and repeat (RD) inhaled doses of a novel phosphoinositide 3-kinase δ inhibitor (PI3Kδ), GSK2269557, administered to healthy smokers Source: International Congress 2014 – New drugs for asthma, COPD and pulmonary fibrosis Year: 2014 Safety and tolerability of the NE inhibitor BAY 85-8501 in patients with non-CF bronchiectasis Source: International Congress 2016 – Preclinical pharmacology: drug targets and mechanisms of action Year: 2016 In vitro profile of the new inhaled pan-JAK inhibitor LAS194046 Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs Year: 2014 Favorable human safety, pharmacokinetics and pharmacodynamics of the autotaxin inhibitor GLPG1690, a potential new treatment in COPD Source: International Congress 2015 – Advances in the future treatment of COPD Year: 2015 A double blind placebo controlled study to assess the effect of roflumilast in addition to LABA/LAMA/ICS treatment in COPD patients using novel biomarkers Source: International Congress 2014 – Clinical trials of drugs for respiratory diseases Year: 2014 Safety, pharmacokinetics, and pharmacodynamics of TD-8236, an inhaled pan-JAK inhibitor, following single- and multiple-ascending doses in healthy volunteers and mild asthmatics Source: Virtual Congress 2021 – Clinical trials in airway diseases: novel treatments and new evidence Year: 2021 Safety, tolerability and pharmacokinetics (PK) of single and repeat nebulised doses of a novel phosphoinositide 3-kinase Δ inhibitor (PI3KΔ), GSK2269557, administered to healthy male subjects in a phase I study Source: Annual Congress 2013 –Novel drugs and biomarkers in respiratory medicine Year: 2013 Pharmacokinetics (PK), safety and tolerability of abediterol and mometasone furoate fixed- and free-dose combinations in healthy subjects Source: International Congress 2014 – Novel approaches and evidence for drug development in respiratory diseases Year: 2014 Safety, tolerability and pharmacokinetics (PK) of AZD8154 (a selective PI3K?d inhibitor) after single ascending inhaled doses in healthy volunteers Source: International Congress 2019 – Airway inflammation: pharmacological mechanisms and novel targets Year: 2019 In vivo efficacy of CHF6001, an inhaled PDE4 inhibitor with a wide therapeutic window Source: International Congress 2014 – Animal models in respiratory drug development Year: 2014 Effect of the CYP3A4 inhibitor ketoconazole on the pharmacokinetics and pharmacodynamics of AZD5069, an oral CXCR2 antagonist Source: International Congress 2014 – Novel evidence relating to respiratory treatment development Year: 2014 Safety, tolerability and pharmacokinetics of an oral competitive reversible CRTh2 antagonist, QAW039, in healthy subjects Source: International Congress 2014 – Allergy and asthma: novel findings based on human cell biology Year: 2014 Safety, immunogenicity and pharmacokinetics (PK) of a 120 mg/kg/week dose of alpha1-proteinase inhibitor in alpha1-antitrypsin deficiency Source: Annual Congress 2013 –COPD drugs: new findings Year: 2013 Safety, tolerability and pharmacokinetics of QAV680, an oral CRTh2 antagonist, in healthy subjects Source: International Congress 2014 – Allergy and asthma: novel findings based on human cell biology Year: 2014 The safety, PK and PD profile of ADC3680, a potent and selective CRTh2 antagonist, in healthy volunteers and partly controlled atopic asthmatic subjects Source: Annual Congress 2013 –New clinical trials of asthma and COPD drugs Year: 2013