The effect of AZD9567 vs. prednisolone on glycaemic control in patients with type 2 diabetes mellitus: Results from a phase 2a clinical trial.

Aims: Corticosteroids are the treatment of choice for many inflammatory diseases but often lead to adverse effects, including hyperglycaemia. This study investigated the mechanisms driving differential effects on glucose control for AZD9567, an oral nonsteroidal selective glucocorticoid receptor modulator vs. prednisolone in 46 patients with type 2 diabetes mellitus.

AZD9567 versus prednisolone in patients with active rheumatoid arthritis: A phase IIa, randomized, double-blind, efficacy, and safety study.

Oral corticosteroid use is limited by side effects, some caused by off-target actions on the mineralocorticoid receptor that disrupt electrolyte balance. AZD9567 is a selective, nonsteroidal glucocorticoid receptor modulator. The efficacy, safety, and tolerability of AZD9567 and prednisolone were assessed in a phase IIa study.

Safety, Pharmacokinetics and Pharmacodynamics of the Selective Glucocorticoid Receptor Modulator Velsecorat (AZD7594) Following Inhalation in Healthy Volunteers.

Introduction: Velsecorat (AZD7594) is a non-steroidal, selective, glucocorticoid receptor modulator (SGRM), being developed for the treatment of asthma. This article reports the initial, first-in-human, single and repeat dose-escalating study in healthy male volunteers.

Methods: The study comprised two parts, a single ascending dose part (n=47) and a multiple ascending dose part (n=26).

Characterization of Clinical Absorption, Distribution, Metabolism, and Excretion and Pharmacokinetics of Velsecorat Using an Intravenous Microtracer Combined with an Inhaled Dose in Healthy Subjects.

This open-label, single-period study describes the human absorption, distribution, metabolism, excretion, and pharmacokinetics of velsecorat (AZD7594). Healthy subjects received inhaled velsecorat (non-radiolabeled; 720 g) followed by intravenous infusion of carbon 14 (C)-velsecorat (30 g). Plasma, urine, and feces were collected up to 168 hours post-dose.

Estimation of Equipotent Doses for Anti-Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator.

AZD9567 is a potent and selective nonsteroidal oral glucocorticoid receptor modulator. It is developed as an anti-inflammatory drug with improved safety profile compared with steroids like prednisolone. Throughout the clinical development of AZD9567, dose selection and data interpretation require a method for determining doses with the same anti-inflammatory effect as prednisolone.

Effects of a selective glucocorticoid receptor modulator (AZD9567) versus prednisolone in healthy volunteers: two phase 1, single-blind, randomised controlled trials.

Background: Glucocorticoids are highly effective and widely used anti-inflammatory drugs, but their use is limited by serious side-effects, including glucocorticoid-induced hyperglycaemia and diabetes. AZD9567 is a non-steroidal, selective glucocorticoid receptor modulator that aims to reduce side-effects. We aimed to assess the safety, tolerability, and pharmacokinetics of AZD9567 in healthy volunteers.

Safety, pharmacokinetics and pharmacodynamics of the selective glucocorticoid receptor modulator AZD7594, following inhalation in healthy Japanese volunteers.

Introduction: AZD7594 is a non-steroidal, selective, glucocorticoid receptor modulator (SGRM), currently in development for the treatment of asthma and chronic obstructive pulmonary disease. This paper reports a randomized placebo-controlled dose escalation study in healthy Japanese male subjects.

Methods: Inhaled AZD7594 was administered as one single dose at day 1 (day 1-4), with subsequent multiple daily doses (day 5-16) via a multiple-dose dry powder inhaler for 12 days of once-daily treatment.

Dipeptidyl Peptidase 1 Inhibitor AZD7986 Induces a Sustained, Exposure-Dependent Reduction in Neutrophil Elastase Activity in Healthy Subjects.

Neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), are activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation. High NSP levels can be detrimental, particularly in lung tissue, and inhibition of NSPs is therefore an interesting therapeutic opportunity in multiple lung diseases, including chronic obstructive pulmonary disease (COPD) and bronchiectasis. We conducted a randomized, placebo-controlled, first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of the DPP1 inhibitor AZD7986 in healthy subjects.

Pharmacokinetics of the Inhaled Selective Glucocorticoid Receptor Modulator AZD5423 Following Inhalation Using Different Devices.

AZD5423 is a non-steroidal glucocorticoid receptor modulator, with low aqueous solubility, developed for treatment of asthma and COPD. In this work, we aim to evaluate and compare the absorption pharmacokinetics (PK) of AZD5423 after inhalation via four devices, (Spira®, I-neb®, Turbuhaler® and a new dry powder inhaler (new DPI)) with two formulations using differently sized primary particles, and to compare the pulmonary bioavailability with the predicted lung deposited dose. Plasma concentration-time data after intravenous, oral and inhaled administration via four devices were available from two clinical studies in healthy and asthmatic subjects.

Efficacy and Tolerability of an Inhaled Selective Glucocorticoid Receptor Modulator - AZD5423 - in Chronic Obstructive Pulmonary Disease Patients: Phase II Study Results.

AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthma patients improved lung function and airway hyper-reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double-blind, randomized and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic patients with COPD (average pre-bronchodilator forced expiratory volume in one-second (FEV1) at screening was 50-52% of predicted normal).

Safety, Pharmacokinetics and Pharmacodynamics of the Selective Glucocorticoid Receptor Modulator AZD5423 after Inhalation in Healthy Volunteers.

AZD5423 is a selective glucocorticosteroid receptor modulator developed for the inhaled use in asthma and COPD. This study reports the initial, first-in-man, single and repeat dose-escalating studies in healthy male individuals, including one cohort of male Japanese individuals. Inhaled, nebulized AZD5423 was safe and well tolerated up to and including the highest doses tested for up to 2 weeks of once-daily treatment.