mizacorat (AZD9567) / AstraZeneca - LARVOL DELTA

Reactivation of latent HIV-1 by the glucocorticoid receptor modulator AZD9567. (PubMed, J Virol) - "Conversely, the GR antagonist mifepristone suppresses HIV-1 LTR-driven gene expression. This drug, AZD9567, was previously tested in clinical trials for rheumatoid arthritis. Mutational analyses shed light on the underlying mode of action and revealed transcription factor binding sites in the HIV-1 LTR that determine responsiveness to AZD9567."

Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD4

Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes (clinicaltrials.gov) - P2 | N=46 | Completed | Sponsor: AstraZeneca | Phase classification: P2a ➔ P2

Phase classification • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The effect of AZD9567 vs. prednisolone on glycaemic control in patients with type 2 diabetes mellitus: Results from a phase 2a clinical trial. (PubMed, Br J Clin Pharmacol) - P2a | "AZD9567 significantly reduced treatment-induced hyperglycaemia compared with prednisolone."

Clinical • Journal • P2a data • Diabetes • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus

AZD9567 versus prednisolone in patients with active rheumatoid arthritis: A phase IIa, randomized, double-blind, efficacy, and safety study. (PubMed, Clin Transl Sci) - "In vitro transcriptomic analysis showed that anti-inflammatory responses were similar for AZD9567, prednisolone, and dexamethasone. The safety profile was not different from that of prednisolone. Larger studies of longer duration are required to determine whether AZD9567 40 mg may in the future be an alternative to prednisolone in patients with inflammatory disease."

Clinical • Journal • P2a data • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Biased regulation of glucocorticoid receptors signaling. (PubMed, Biomed Pharmacother) - "Based on the bias regulation of GR, selective GR agonists and modulators (SEGRAMs) were developed to bias therapeutic outcomes toward expected outcomes (e.g., anti-inflammation and immunoregulation) by influencing GR-mediated gene expression. This paper provides a review of the bias regulation and mechanism of GR and the research progress of drugs."

Journal • Review • Immune Modulation • Inflammation

Discovery of Novel GR Ligands toward Druggable GR Antagonist Conformations Identified by MD Simulations and Markov State Model Analysis. (PubMed, Adv Sci (Weinh)) - "To understand the allosteric communication within the GR ligand binding domain, the folding pathway of helix 12 (H12) induced by the binding of the agonist dexamethasone (DEX), antagonist RU486, and modulator AZD9567 are explored by molecular dynamics simulations and Markov state model analysis. HP-19 also does not induce adverse effect-related transactivation functions of GR. The novel ligands discovered here may serve as promising starting points for the development of GR modulators."

Journal

Molecular View on the Dissociation Pathways and Transactivation Regulation Mechanism of Nonsteroidal GR Ligands. (PubMed, J Chem Inf Model) - "Notably, the binding of AZD9567 poses a substantial impact on the conformation of the GR homodimer interface, which provides a valuable clue to understand the mechanisms of the TA-related side effects induced by the adjustments of the homodimerization process. These findings are critical for the structure-based rational design of novel GR ligands with more potent anti-inflammatory potency and reduced side effects."

Journal

Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes (clinicaltrials.gov) - P2a; N=46; Completed; Sponsor: AstraZeneca; Active, not recruiting ➔ Completed

Clinical • Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • TNFA

[VIRTUAL] AZD9567 versus prednisolone in patients with active rheumatoid arthritis: a phase 2a, randomised, double-blind, parallel-group efficacy and safety study (EULAR 2021) - No abstract available

Clinical • P2a data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

[VIRTUAL] AZD9567 VERSUS PREDNISOLONE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: A PHASE 2A, RANDOMISED, DOUBLE-BLIND, PARALLEL-GROUP EFFICACY AND SAFETY STUDY (EULAR 2021) - P2a | "AZD9567 40 mg had a similar efficacy profile to prednisolone 20 mg in patients with active RA. Both drugs were well tolerated, with no new safety signals. Unlike prednisolone, AZD9567 had no effect on serum sodium/potassium ratio, suggesting selectivity of AZD9567 for the GR over the MR."

Clinical • P2a data • CNS Disorders • Depression • Immunology • Inflammatory Arthritis • Psychiatry • Rheumatoid Arthritis • Rheumatology • CRP

Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes (clinicaltrials.gov) - P2a; N=37; Active, not recruiting; Sponsor: AstraZeneca; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes (clinicaltrials.gov) - P2a; N=42; Recruiting; Sponsor: AstraZeneca; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

An early phase study in patients with Type 2 Diabetes to assess the effect on glucose homeostasis of two dose levels of AZD9567, compared to Prednisolone (clinicaltrialsregister.eu) - P2; N=46; Ongoing; Sponsor: AstraZeneca AB, 151 85 Södertälje, Sweden

Clinical • New P2 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes (clinicaltrials.gov) - P2a; N=46; Not yet recruiting; Sponsor: AstraZeneca

Clinical • New P2a trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Estimation of equipotent doses for anti-inflammatory effects of prednisolone and AZD9567, an oral selective non-steroidal glucocorticoid receptor modulator. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Specifically, 20 mg prednisolone was estimated to be equipotent to 40 mg AZD9567 (95 % CI: 29 - 54 mg). Static concentration-response analyses showed that the relative potencies for inhibition of TNFα release of AZD9567 and prednisolone were well aligned with several other pro-inflammatory cytokines."

Journal

Early Phase Study to Assess Efficacy and Safety of AZD9567 Versus Prednisolone in Patients With Rheumatoid Arthritis (clinicaltrials.gov) - P2a; N=21; Completed; Sponsor: AstraZeneca; Recruiting ➔ Completed; N=40 ➔ 21

Clinical • Enrollment change • Trial completion

Early Phase Study to Assess Efficacy and Safety of AZD9567 Versus Prednisolone in Patients With Rheumatoid Arthritis (clinicaltrials.gov) - P2a; N=40; Recruiting; Sponsor: AstraZeneca; Trial completion date: Sep 2020 ➔ Jan 2020; Trial primary completion date: Sep 2020 ➔ Jan 2020

Clinical • Trial completion date • Trial primary completion date

Early Phase Study to Assess Efficacy and Safety of AZD9567 Versus Prednisolone in Patients With Rheumatoid Arthritis (clinicaltrials.gov) - P2a; N=40; Recruiting; Sponsor: AstraZeneca; Trial completion date: Aug 2019 ➔ Sep 2020; Trial primary completion date: Aug 2019 ➔ Sep 2020

Clinical • Trial completion date • Trial primary completion date

Newly added product (AstraZeneca Press Release) - P2, Rheumatoid Arthritis

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