Delving into the Latest Updates on AZD-9164 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

mAChRs

Mechanism

mAChRs antagonists(Muscarinic acetylcholine receptor antagonists)

Therapeutic Areas

Respiratory Diseases

Active Indication-

Inactive Indication

Pulmonary Disease, Chronic Obstructive

Originator Organization

AstraZeneca Pharmaceuticals Co. Ltd.

Active Organization-

Inactive Organization

AstraZeneca PLC

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC29H38FN2O2

InChIKeyFNYFFCOCVNTJCD-NNMXADRKSA-N

CAS Registry1034978-04-5

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A Phase I, Multi Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of AZD9164 Given Once Daily as Inhaled Formulation Via Turbuhaler for 13 Days in Healthy Male and Female Subjects and in Patients With Chronic Obstructive Pulmonary Disease (COPD)

The purpose of this study is to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled AZD9164 following administration of multiple ascending doses in healthy male and female subjects and COPD patients.

Start Date01 Dec 2009

Sponsor / Collaborator

AstraZeneca PLC

EUCTR2009-010864-40-SE / Not yet recruitingNot Applicable

A double-blind, double-dummy, placebo-controlled, randomised, multi-centre, 5-way cross-over, single-dose study to investigate the local and systemic effects of inhaled AZD9164 compared to tiotropium in subjects with Chronic Obstructive Pulmonary Disease (COPD)

Start Date18 Jun 2009

Sponsor / Collaborator

AstraZeneca AB

100 Clinical Results associated with AZD-9164

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100 Translational Medicine associated with AZD-9164

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100 Patents (Medical) associated with AZD-9164

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6

Literatures (Medical) associated with AZD-9164

01 Feb 2017·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Long acting muscarinic antagonists for the treatment of chronic obstructive pulmonary disease: a review of current and developing drugs

Q2 · MEDICINE

Review

Author: Mastrodicasa, Mark A. ; Zafar, Muhammad A. ; Droege, Christopher A. ; Mulhall, Aaron M. ; Ernst, Neil E. ; Panos, Ralph J.

INTRODUCTIONLong acting muscarinic receptor antagonists (LAMA) reverse airflow obstruction by antagonizing para-sympathetic bronchoconstricting effects within the airways. For years, tiotropium, has been the cornerstone LAMA for chronic obstructive pulmonary disease (COPD) management. Recently, new agents, aclidinium bromide, glycopyrronium bromide, and umeclidinium bromide, have been developed and introduced into clinical practice. Areas covered: This article reviews the clinical efficacy and adverse effects of currently available LAMAs in COPD treatment as well as developing LAMAs in early clinical trials and preclinical studies (V0162, TD-4208, CHF 5407, AZD9164, AZD8683, bencycloquidium). In addition, a new class of molecule that combines muscarinic antagonist and β2-adrenergic properties (MABA) is described and current developmental progress discussed (GSK-961081, THRX-200495). Expert opinion: Future key areas for developing drugs for the management of COPD include prolonged duration of action, optimal delivery systems, synergistic combinations with other drugs, maximization of benefits and minimization of adverse effects. The development of new LAMA and MABA molecules provides exciting progress towards simpler and more effective COPD management.

01 May 2016·Journal of Pharmacological and Toxicological MethodsQ4 · MEDICINE

PKPD modelling of PR and QRS intervals in conscious dogs using standard safety pharmacology data

Q4 · MEDICINE

Article

Author: Parkinson, Joanna ; Collins, Teresa ; Bergenholm, Linnéa ; Chappell, Michael J ; Evans, Neil D

INTRODUCTIONPharmacokinetic-pharmacodynamic (PKPD) modelling can improve safety assessment, but few PKPD models describing drug-induced QRS and PR prolongations have been published. This investigation aims to develop and evaluate PKPD models for describing QRS and PR effects in routine safety studies.METHODSExposure and telemetry data from safety pharmacology studies in conscious beagle dogs were acquired. Mixed effects baseline and PK-QRS/PR models were developed for the anti-arrhythmic compounds AZD1305, flecainide, quinidine and verapamil and the anti-muscarinic compounds AZD8683 and AZD9164. RR interval correction and circadian rhythms were investigated for predicting baseline variability. Individual PK predictions were used to drive the pharmacological effects evaluating linear and non-linear direct and effect compartment models.RESULTSConduction slowing induced by the tested anti-arrhythmics was direct and proportional at low exposures, whilst time delays and non-linear effects were evident for the tested anti-muscarinics. AZD1305, flecainide and quinidine induced QRS widening with 4.2, 10 and 5.6% μM(-1) unbound drug. AZD1305 and flecainide also prolonged PR with 13.5 and 11.5% μM(-1). PR prolongations induced by the anti-muscarinics and verapamil were best described by Emax models with maximal effects ranging from 55 to 95%. RR interval correction and circadian rhythm improved PR but not QRS modelling. However, circadian rhythm had minor impact on estimated drug effects.DISCUSSIONBaseline and drug-induced effects on QRS and PR intervals can be effectively described with PKPD models using routine data, providing quantitative safety information to support drug discovery and development.

01 Dec 2014·BMC Pulmonary MedicineQ3 · MEDICINE

Transient paradoxical bronchospasm associated with inhalation of the LAMA AZD9164: analysis of two Phase I, randomised, double-blind, placebo-controlled studies

Q3 · MEDICINE

ArticleOA

Author: Carin Jorup ; Ulf Sjöbring ; Thomas Bengtsson ; Kerstin Strandgården

BACKGROUNDAZD9164 has demonstrated potential as an inhaled, long-acting, muscarinic antagonist (LAMA) bronchodilator. However, in patients with COPD, but not in healthy subjects, a transient initial drop in FEV1 was observed following inhalation of nebulised doses of AZD9164 in citrate buffer.Two additional studies were conducted to further assess the safety and tolerability of multiple ascending doses of AZD9164 in 27 white and 18 Japanese healthy subjects and in 4 patients with COPD. In these studies, AZD9164 was inhaled via Turbuhaler™.METHODSThese were Phase I, randomised, double-blind, placebo-controlled, multiple ascending dose (MAD) studies conducted in Sweden and UK. Healthy subjects (mean age 25.9 yrs) and patients with COPD (mean age 66 yrs, mean post-bronchodilator FEV1 60.1% predicted normal value) were randomised 2:1 to active treatment (400, 1000 or 2800 μg delivered doses of AZD9164) or placebo.RESULTSNo safety or tolerability concerns were identified in the healthy subjects at doses up to and including 2800 μg and both studies confirmed the bronchodilator effect of AZD9164. However, the first 3 patients in the COPD cohort who received AZD9164 (1000 μg) experienced a transient fall in FEV1 5 to 15 minutes after inhalation of AZD9164 while the patient receiving placebo did not. The study safety review process then resulted in cessation of further activities on AZD9164. Retrospective analysis showed that two healthy subjects had also had transient falls in FEV1 shortly after inhalation of AZD9164 400 and 2800 μg respectively, although neither reported any related respiratory symptoms or other AEs.CONCLUSIONSThese results show that transient paradoxical bronchoconstriction can occur in some healthy subjects, in addition to patients with COPD, following inhalation of AZD9164 and that the citrate buffer used in the nebulised formulation cannot have been the only cause of the drop in FEV1 in previous studies. As preclinical data do not provide an explanation, the reasons for this brief post-dose drop in FEV1 remain unclear. However, these results highlight the importance of monitoring lung function immediately post-dose when investigating novel inhaled treatments, even when a rapid onset of effect is not expected.TRIAL REGISTRATIONClinicaltrials.gov NCT01016951 and NCT01096563.

100 Deals associated with AZD-9164

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pulmonary Disease, Chronic Obstructive	Phase 2	SE	AstraZeneca PLC	01 Jun 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00939211 (Pubmed \| Respir Med)	Phase 2	Pulmonary Disease, Chronic Obstructive	28	AZD9164 100 μg	(kiiysyfjxm) = otwcxnzqro bucfqnktqn (agdlzomdbz )	-	01 Jan 2013
				AZD9164 400 μg	(kiiysyfjxm) = kxepfdfcky bucfqnktqn (agdlzomdbz )