RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study.

Background: This study was a randomised, double-blind, placebo-controlled study intended to establish the translatability of the RLS-0071 mechanisms of action from animal disease models to humans by inhibiting neutrophil-mediated inflammation at the tissue level and major inflammatory biomarkers. We hypothesised that RLS-0071 inhibits a temporary neutrophil-mediated inflammation in the lungs induced by inhalation of low-dose lipopolysaccharide (LPS) in healthy participants.

Methods: Participants were randomised to one of three arms to receive inhaled LPS followed by three doses of either low-dose (10 mg·kg) or high-dose (120 mg·kg loading dose followed by two doses of 40 mg·kg) RLS-0071 or placebo (saline) every 8 h.

Novel cathepsin C inhibitor, BI 1291583, intended for treatment of bronchiectasis: Phase I characterization in healthy volunteers.

Novel treatments are needed to reduce inflammation, improve symptoms, address exacerbations, and slow disease progression in bronchiectasis. Cathepsin C (CatC) inhibition promises to achieve this through reduction of neutrophil-derived serine protease (including neutrophil elastase [NE] and proteinase 3 [PR3]) activation. Here, we present the phase I characterization of the novel CatC inhibitor, BI 1291583.

The preclinical and phase 1 development of the novel oral cathepsin C inhibitor BI 1291583.

https://bit.ly/47PZ8E5.

Sodium Chloride versus Lactose as a Carrier for House Dust Mite Allergen in Allergen Chamber Studies: A Clinical Study to Assess Noninferiority.

Introduction: In the Fraunhofer allergen challenge chamber (ACC), a standardized, universal, good manufacturing practice-conforming technology using a spray dried solution of lactose (L) and allergen extract has been established. In this study, we investigated the noninferiority of hypertonic sodium chloride (S) versus L as a carrier for house dust mite (HDM) allergen to simplify manufacturing, reduce costs, and allow for wider use.

Methods: Using a participant-blinded, sham exposure-controlled, single-arm, sequential intervention study, we challenged adults with HDM allergic rhinitis five times in the ACC.

The effect of bradykinin 1 receptor antagonist BI 1026706 on pulmonary inflammation after segmental lipopolysaccharide challenge in healthy smokers.

Background: Bradykinin 1 receptor (B1R) signalling pathways may be involved in the inflammatory pathophysiology of chronic obstructive pulmonary disease (COPD). B1R signalling is induced by inflammatory stimuli or tissue injury and leads to activation and increased migration of pro-inflammatory cells. Lipopolysaccharide (LPS) lung challenge in man is an experimental method of exploring inflammation in the lung whereby interference in these pathways can help to assess pharmacologic interventions in COPD.

Occupational exposure to veterinary antibiotics: Pharmacokinetics of enrofloxacin in humans after dermal, inhalation and oral uptake - A clinical study.

Occupational exposure to veterinary antibiotics in hen houses at poultry feeding farms was demonstrated by biomonitoring campaigns in the past. The objective of this study was to investigate pharmacokinetics of three uptake routes: dermal, oral and inhaled. In an open-label cross-over study, six healthy volunteers were exposed to single occupational relevant doses of enrofloxacin.

Efficacy and Safety of a Drug-Free, Barrier-Forming Nasal Spray for Allergic Rhinitis: Randomized, Open-Label, Crossover Noninferiority Trial.

Introduction: Symptoms of allergic rhinitis can be reduced by nonpharmacological nasal sprays that create a barrier between allergens and the nasal mucosa. A new nasal spray (AM-301) containing the clay mineral bentonite was tested for its ability to reduce symptoms of grass pollen.

Methods: This open-label, crossover, noninferiority trial compared the efficacy and safety of AM-301 to that of hydroxypropyl methylcellulose (HPMC; Nasaleze® Allergy Blocker), an established barrier method.

Lung pharmacokinetics of inhaled and systemic drugs: A clinical evaluation.

Background And Purpose: Human pharmacokinetic studies of lung-targeted drugs are typically limited to measurements of systemic plasma concentrations, which provide no direct information on lung target-site concentrations. We aimed to evaluate lung pharmacokinetics of commonly prescribed drugs by sampling different lung compartments after inhalation and oral administration.

Experimental Approach: Healthy volunteers received single, sequential doses of either inhaled salbutamol, salmeterol and fluticasone propionate (n = 12), or oral salbutamol and propranolol (n = 6).

Effects of Recombinant Human Angiotensin-Converting Enzyme 2 on Response to Acute Hypoxia and Exercise: A Randomised, Placebo-Controlled Study.

Introduction: Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system (RAS) that has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). Enhancing ACE2 activity using GSK2586881, a recombinant form of human ACE2, could be beneficial in diseases such as ARDS but may blunt the hypoxic pulmonary vasoconstriction (HPV) response and potentially impact systemic and tissue oxygenation. This study aimed to evaluate the effect of GSK2586881 0.

Investigating the effect of TRPV4 inhibition on pulmonary-vascular barrier permeability following segmental endotoxin challenge.

Background: Acute Respiratory Distress Syndrome (ARDS) is associated with increased pulmonary-vascular permeability. In the lung, transient receptor potential vanilloid 4 (TRPV4), a Ca-permeable cation channel, is a regulator of endothelial permeability and pulmonary edema. We performed a Phase I, placebo-controlled, double-blind, randomized, parallel group, proof-of-mechanism study to investigate the effects of TRPV4 channel blocker, GSK2798745, on pulmonary-vascular barrier permeability using a model of lipopolysaccharide (LPS)-induced lung inflammation.

The first-in-human study of CNTO 7160, an anti-interleukin-33 receptor monoclonal antibody, in healthy subjects and patients with asthma or atopic dermatitis.

Aims: To assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of CNTO 7160, an anti-interleukin-33 receptor (IL-33R) monoclonal antibody, in healthy subjects and patients with asthma or atopic dermatitis (AD).

Methods: In Part 1 of this Phase I, randomized, double-blind, placebo-controlled study, healthy subjects (n = 68) received single ascending intravenous (IV) CNTO 7160 dose (0.001 to 10 mg/kg) or placebo.

The Effect of a Thixotropic Nasal Gel on Nasal Symptoms and Inflammatory Biomarkers in Seasonal Allergic Rhinitis.

Background: Drug-free viscous nasal applications have been shown to reduce nasal symptoms in individuals with seasonal allergic rhinitis (SAR). Nascum®-Plus (NP), a commercially available thixotropic gel, has been designed to reduce dryness and soreness of the nasal mucosa and prevent the absorption of small particles.

Objectives: The aim of this study was to assess the efficacy of single-dose NP in treating nasal symptoms and secretion during challenge in an allergen challenge chamber (ACC).

Safety, pharmacokinetics and pharmacodynamics of a novel anti-asthmatic drug, XC8, in healthy probands.

Introduction: XC8 (histamine glutarimide) is a novel agent which targets eosinophilic migration and mast cell degranulation and has shown anti-asthmatic effects in animal studies.

Objective: The objective of this placebo-controlled phase 1 study was to assess the safety of oral XC8 and to evaluate its pharmacokinetic and pharmacodynamic properties.

Methods: 32 healthy volunteers in three dose-escalation treatment groups (10 mg [n = 8], 50 mg [n = 8] and 200 mg [n = 16]) were randomized in a 3:1 ratio to XC8 or placebo respectively.

Phase 1 pharmacokinetics and phase 3 efficacy of testosterone nasal gel in subjects with seasonal allergies.

Introduction: NATESTO testosterone nasal gel (TNG) is a liquid gel that is applied in the nose for the treatment of male hypogonadism. There is a reasonable concern that administration of TNG to patients with active rhinitis could modify absorption. Results from two clinical studies are reported wherein subjects with allergic rhinitis (AR) subjects are treated with TNG.

Specificity and reproducibility of nasal biomarkers in patients with allergic rhinitis after allergen challenge chamber exposure.

Background: Allergic rhinitis is an inflammatory disease that causes cellular influx and mediator release in the nose. These inflammatory changes might be used as nasal biomarkers to assess the efficacy of novel anti-allergic treatments.

Objective: To assess the specificity and reproducibility of nasal biomarkers in patients with allergic rhinitis after grass pollen exposure in an allergen challenge chamber.

Efficacy and safety of a novel nasal steroid, S0597, in patients with seasonal allergic rhinitis.

Background: Allergic rhinitis (AR) poses a significant global burden with increasing prevalence. Although intranasal glucocorticosteroids are effective, older agents can have limiting side effects. S0597, a novel intranasal glucocorticosteroid, has demonstrated good safety and tolerability during preclinical and phase 1 studies.

Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge chamber.

Background: It has frequently been speculated that pruritus and skin lesions develop after topical exposure to aeroallergens in sensitized patients with atopic dermatitis (AD).

Objective: We sought to study cutaneous reactions to grass pollen in adult patients with AD with accompanying clear IgE sensitization to grass allergen in an environmental challenge chamber using a monocenter, double-blind, placebo-controlled study design.

Methods: Subjects were challenged on 2 consecutive days with either 4000 pollen grains/m(3) of Dactylis glomerata pollen or clean air.

Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis.

Background: The inflammatory response in patients with seasonal allergic rhinitis (SAR) is partly mediated by the prostaglandin D2 receptor chemoattractant receptor homologous molecule on T(H)2 cells (CRTH2).

Objective: We sought to investigate the efficacy and safety of the oral CRTH2 antagonist BI 671800 (50, 200, and 400 mg twice daily), fluticasone propionate nasal spray (200 μg once daily), or oral montelukast (10 mg once daily) administered for 2 weeks in patients with SAR.

Methods: In this randomized, double-blind, placebo-controlled, partial-crossover study, participants aged 18 to 65 years with a positive skin prick test to Dactylis glomerata pollen were exposed to out-of-season allergen in the environmental challenge chamber for 6 hours.

Pollen starch granules in bronchial inflammation.

Background: Pollen grains with a diameter of more than 10 μm preferentially deposit in the upper airways. Their contribution to lower airway inflammation is unclear. One hypothesis is that lower airway inflammation is mainly caused by allergen containing pollen starch granules, which are released from the pollen grains and can easily enter the peripheral airways because of their smaller size.

Anti-allergic drug testing in an environmental challenge chamber is suitable both in and out of the relevant pollen season.

Background: An environmental challenge chamber (ECC) is a useful tool to expose allergic patients to relevant allergens in a controlled indoor setting and to test anti-allergic treatment. Hitherto, ECC studies with grass pollen are conducted primarily outside of the pollen season to avoid the influence of natural pollen exposure.

Objective: To investigate whether an established anti-allergic treatment, a combination of cetirizine (CET) and pseudoephedrine (PSE), shows an equivalent treatment effect within and outside of the grass pollen season when tested in an ECC.